Virtual Library

Background:
CC-486 (oral azacitidine) is an epigenetic modifier with potential effect as a priming agent for chemotherapy in patients with NSCLC. Outcomes of nab-paclitaxel+CC-486 vs nab-paclitaxel as second-line treatment of advanced NSCLC are reported.

Method:
Patients with advanced nonsquamous NSCLC and no more than 1 prior chemotherapy line (including platinum doublet combination) were randomized (1:1) to nab-paclitaxel 100 mg/m[2] d8, 15 + CC-486 200 mg qd d1-14 or nab-paclitaxel 100 mg/m[2] d1, 8, both administered q3w until progressive disease/unacceptable toxicity. Primary endpoint was PFS. Secondary endpoints: DCR, ORR, OS, and safety. QoL, an exploratory endpoint, was assessed on d1 of each cycle.

Result:
The nab-paclitaxel+CC-486 arm was discontinued in October 2016 due to demonstrated futility vs nab-paclitaxel monotherapy upon completion of a protocol-specified interim analysis. Overall, 161 patients were randomized (nab-paclitaxel+CC-486, 81; nab-paclitaxel, 80). Baseline characteristics were balanced between arms. The median number of cycles was 4 for each arm, and the median nab-paclitaxel cumulative dose was 600 mg/m[2] and 800 mg/m[2] in the nab-paclitaxel+CC-486 and nab-paclitaxel arms, respectively. Rates of grade 3/4 (G3/4) treatment-emergent AEs were 59.5% and 54.4% for the combination and monotherapy arms, respectively. The most frequent hematologic G3/4 AEs were neutropenia (16.5% vs 10.1%) and anemia (1.3% vs 7.6%). G3/4 peripheral neuropathy was reported in 2.5% and 7.6% of patients, respectively. The addition of CC-486 to nab-paclitaxel did not improve ORR, DCR, PFS, or OS (Table). When assessed by Lung Cancer Symptom Scale, nab-paclitaxel monotherapy was associated with improvement in the global QoL, average symptom burden index, and lung cancer symptoms except for hemoptysis.

Conclusion:
The addition of CC-486 to nab-paclitaxel did not clinically benefit patients with previously treated NSCLC. However, single-agent nab-paclitaxel appears to be a promising therapy based on safety, efficacy, and QoL data. Updated efficacy and safety data will be presented. NCT02250326

	nab-Paclitaxel + CC-486 n = 81	nab-Paclitaxel n = 80
Median PFS, months	3.2	4.2
HR (95% CI)	1.3 (0.9 - 2.0)
1-year PFS, %	4.1	18.3
Median OS, months	8.4	12.7
HR (95% CI)	1.4 (0.88 - 2.31)
1-year OS, %	39.2	54.3
ORR, n (%)[a]	11 (13.6)	11 (13.8)
Response rate ratio (95% CI)	0.99 (0.45 - 2.15)
CR PR SD PD DCR (≥ SD)	0 11 (13.6) 41 (50.6) 22 (27.2) 52 (64.2)	0 11 (13.8) 43 (53.8) 19 (23.8) 54 (67.5)
CR, complete response; DCR, disease control rate; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. [a] Response rate was based on the intent-to-treat population; however, 14 patients did not have a response assessment.

Background:
Vitamin B12 and folic acid supplementation(B12-FAS) reduces the incidence and severity of hematological toxicity[HTox] in pemetrexed-based chemotherapy. It is recommended to initiate B12-FAS 5-7 days before the first cycle. Observational and prospective single-arm studies have not shown any increase in HTox when pemetrexed was started earlier than the recommended duration of B12-FAS.

Method:
An open-label, randomized trial (PEMVITASTART; NCT02679443) was conducted to evaluate differences in HTox between patients initiated on pemetrexed-platinum chemotherapy following 5-7 days of B12-FAS (Delayed Arm; DA) versus those receiving B12-FAS simultaneously(≤24 hours) with chemotherapy initiation (Immediate Arm; IA). Eligible patients had locally advanced/metastatic non-squamous NSCLC AND ECOG PS=0-2. Block randomization was 1:1 into DA and IA. All enrolled patients received 3-weekly pemetrexed-platinum doublet [500mg/m[2] AND cisplatin(65mg/m[2]) OR carboplatin(AUC 5.0mg/mL/min) each on D1] for maximum of six cycles. Supplementation was 1000µgm FA PO daily and 3-weekly 1000µgm i/m vitamin B12. Primary outcome was any grade HTox while secondary outcomes were grade 3/4 HTox, relative dose intensity(RDI) delivered, inter-cycle delays(ICDs), supportive therapies usage (ESA/G-CSF/PRBC transfusions) and changes in serum levels of B12/FA/homocysteine.

Result:
Of 161 patients recruited (81 IA, 80 DA), 150 patients (77 IA, 73 DA) received ≥1 cycle and were included in modified ITT analysis. Baseline parameters were matched except for gender (IA=10.4%, DA=23.3%, p=0.03) and baseline thrombocytopenia (IA=7.8%, DA=0%, p=0.03). Baseline anemia(Hb<12gm/dL) was present in 34.7% (IA=32.5%, DA=37.0%; p=0.56). Incidence of any grade anemia, leukopenia, neutropenia and thrombocytopenia was 87.0% vs. 87.7%(p=0.90), 37.7% vs. 28.8%(p=0.25), 20.8% vs. 15.1%(p=0.36) and 31.2% vs. 16.4%(p=0.04) in IA and DA respectively. Grade 3/4 anemia was 18.2% vs. 12.3%(p=0.32) in IA and DA respectively while other cytopenias were similar (<5% in each arm). Supportive therapies usage in IA vs. DA were 22.1% vs. 12.3% for PRBC transfusions (p=0.12), 3.9% vs. 6.8% for G-CSF (p=0.49) and 10.4% vs. 1.4% for ESAs (p=0.03). ICDs occurred in 14.3% of IA vs. 8.2% in DA (p=0.24). RDI delivered (median 93.5% for pemetrexed and 91.0% for platinum) was similar in both arms. Following continued B12-FAS, after C3(compared to baseline), serum homocysteine was lower (median 10.0µmol/L vs. 17.6µmol/L;p<0.001) while FA (median 17.9ng/ml vs. 5.7ng/ml;p<0.001) and B12 levels (mean 1926.3pg/ml vs. 880.2pg/ml;p<0.001) were higher. In DA, serum FA and B12 on Day1 of C1(following 5-7days of B12-FAS) were significantly higher than baseline but homocysteine levels were similar.

Conclusion:
Simultaneous B12-FAS initiation with pemetrexed-based chemotherapy is feasible with acceptable HTox profile. Serum homocysteine levels are unaffected by 5-7 days of B12-FAS.

Background:
A previous phase III randomized trial improved overall survival of patients with advanced or relapsed squamous cell lung carcinoma, compared with cisplatin plus docetaxel. However, evaluation of nedaplatin plus docetaxel’s effect on progression free survival (PFS) and time to progression (TTP) was limited.

Method:
To compare the efficacy and safety of nedaplatin plus docetaxel and cisplatin plus docetaxel. In this randomized, open-label, multicenter trial, patients diagnosed with advanced or relapsed squamous cell carcinoma pathologically or cytologically were enrolled in China. All the patients have no previous oncology medication. Patients were randomly assigned (1:1) to 80 mg/m² nedaplatin and 75 mg/m² docetaxel intravenously, or 75 mg/m² cisplatin and 75 mg/m² docetaxel, every 3 weeks for four cycles. The primary end points was PFS. Secondary endpoints included TTP and best overall response. The efficacy endpoint were analyzed in the intention-to-treat set and in the per protocol set. （Clinical trial number: NCT02088515; Funding:Jiangsu Simcere Pharmaceutical Co., Ltd.）

Result:
From December 2013 to December 2015, 286 patients were randomly assigned. Two hundred and eighty patients were included in the modified intention-to-treat analysis (141 in the nedaplatin group and 139 in the cisplatin group). In the intention-to-treat analysis set, median PFS was 4.63 months (95% confidence interval (CI), 4.43-5.10) in the nedaplatin group and 4.23 months (95% CI, 3.37-4.53) in the cisplatin group. PFS did not differ significantly between two groups (log-rank test, p =0.056). In per protocol set, PFS was significantly longer in the nedaplatin group (median 4.63 months, 95% CI, 4.43-5.10) than in the cisplatin group (median 4.27 months, 95% CI, 3.37-4.53; hazard ratio 0.760, 95% CI 0.585-0.989; p=0.039, log-rank test). Best overall response and TTP were improved in nedaplatin group than in cisplatin group (p= 0.002, median 4.57(4.30-4.80) vs 3.67(3.13-4.43) p= 0.020, respectively) in the intention-to-treat analysis set. Grade III or IV adverse events was more frequent in the cisplatin group than in the nedaplatin group (46 of 141 patients in the nedaplatin group and 62 of 139 in the cisplatin group, p=0.039). Grade 3 or worse nausea (0 vs 7) and fatigue (1 vs 3) were more frequent in the cisplatin group than in the nedaplatin group.

Conclusion:
There was no significant difference of PFS between cisplatin group and nedaplatin group. However, more adverse events was observed in the cisplatin group than in the nedaplatin group. Nedaplatin plus docetaxel could be a new treatment option for advanced or relapsed squamous cell lung cancer.

Abstract not provided

Background:
Although brain metastases (BM) are a very common and clinically challenging for NSCLC progression, there are few prospective studies addressing the safety and efficacy of bevacizumab in combination with chemotherapy in patients with BM. This study aimed to describe the characteristics of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced NSCLC (aNSCLC), with BM or not, in routine clinical practice.

Method:
For this French non-interventional, prospective, and multicenter study, data were collected every 3 months over an 18-month period, from bevacizumab initiation. End points were progression-free survival (PFS), overall survival (OS), treatment use, and safety.

Result:
Amongst the 407 aNSCLC patients analyzed, the 84 patients (21%) with BM at bevacizumab initiation had poorer general health than patients without BM (ECOG 2: 16% versus 11%). All except for 2 patients received bevacizumab (7.5 or 5 mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. After a median follow-up of 10.8 months (range: 0.2-34.1), median PFS and OS were not significantly different between patients with or without BM. BM was not found as PFS prognosis factor in multivariate analysis (HR=1.03; 95% CI=[0.79; 1.33], p=0.85). At least one serious adverse event (SAE) was reported in 30% of aNSCLC patients with BM (n=25) and in 32% of patients without BM (n=106); 13% (n=11) and 12% (n=40) of patients experienced at least one bevacizumab-related SAE, respectively. Three patients in each group died from bevacizumab-related events.

	aNSCLC patients with brain metastasis - N=84 (months, [CI 95%])	aNSCLC patients without brain metastasis - N=423 (months, [CI 95%])	Logrank test p value
Median PFS	6.5 [5.7; 8.1]	6.9 [5.9; 7.6]	0.57
Median OS	14.5 [10.0; -]	12.5 [10.1; 14.7]	0.33

Conclusion:
In this study, no differences were observed between advanced NSCLC patients with and without brain metastasis in terms of clinical benefit (survival and safety) from first-line chemotherapy combined with bevacizumab. Nature, severity and outcome of AEs were consistent with the known safety profile of bevazicumab.

Background:
In REVEL, ramucirumab+docetaxel in the second-line (2L) treatment of patients with advanced NSCLC led to improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), independent of histology. This exploratory, post-hoc analysis focuses on patients who progressed rapidly on first-line (1L), and who traditionally have a poor prognosis in the 2L setting. In REVEL, treatment benefit was observed in patients with progressive disease as their best overall response to 1L and in patients who were on 1L for only a short time (Reck M, ASCO 2017, Abstr 9079). Here, we report outcomes from patients who participated in REVEL according to their time to tumor progression (TTP) on 1L (ClinicalTrials.gov, NCT01168973).

Method:
Patients with advanced NSCLC of squamous or nonsquamous histology with disease progression during or after 1L platinum-based chemotherapy were randomized (1:1) to receive docetaxel 75 mg/m[2] and either ramucirumab 10 mg/kg or placebo on day 1 of a 21-day cycle. OS was the primary endpoint. Secondary endpoints included PFS, ORR, safety, and patient-reported quality-of-life (QoL). Response was assessed according to RECIST v1.1. QoL was assessed with the Lung Cancer Symptom Scale. TTP on 1L, defined as the time from start of 1L until progressive disease, was assessed for the REVEL intent-to-treat population.

Result:
Of 1253 patients in REVEL, 11% had TTP ≤9 weeks, 17% had TTP ≤12 weeks, and 28% had TTP ≤18 weeks on 1L therapy. Baseline characteristics of each subgroup generally were balanced between treatment arms. Efficacy, safety, and QoL outcomes by TTP are shown in the table.

Outcomes in Patients From the REVEL Study by Time to Tumor Progression on First-Line Therapy

	≤9 Weeks		≤12 Weeks		≤18 Weeks
INTENT-TO-TREAT POPULATION	Ramucirumab+Docetaxel N = 71	Placebo+Docetaxel N = 62	Ramucirumab+Docetaxel N = 111	Placebo+Docetaxel N = 98	Ramucirumab+Docetaxel N = 182	Placebo+Docetaxel N = 172
Median OS, months (95% Confidence Interval [CI])	8.28 (5.19, 10.84)	4.83 (3.09, 6.90)	9.10 (6.70, 10.84)	5.78 (4.30, 7.49)	8.51 (6.97, 9.95)	5.95 (4.44, 6.97)
Unstratified Hazard Ratio (HR) (95% CI)	0.69 (0.47, 1.01)		0.74 (0.54, 1.00)		0.80 (0.63, 1.01)
12-month survival rate, % (95% CI)	47 (35, 58)	32 (20, 44)	34 (25, 43)	23 (15, 32)	30 (23, 37)	24 (18, 31)
18-month survival rate, % (95% CI)	20 (11, 31)	12 (5, 24)	17 (10, 26)	13 (6, 22)	17 (11, 23)	13 (8, 20)
Median PFS, months (95% CI)	3.01 (2.66, 4.07)	1.48 (1.41, 1.87)	3.61 (2.76, 4.21)	1.61 (1.45, 2.60)	3.22 (2.79, 4.14)	1.61 (1.48, 2.60)
Unstratified HR (95% CI)	0.69 (0.48, 0.98)		0.73 (0.55, 0.97)		0.72 (0.58, 0.89)
ORR (complete response [CR]+partial response [PR]), %, (95% CI)	18.3 (10.1,29.3)	3.2 (0.4, 11.2)	18.9 (12.1, 27.5)	9.2 (4.3, 16.7)	19.2 (13.8, 25.7)	10.5 (6.3, 16.0)
Disease Control Rate (CR+PR+stable disease), % (95% CI)	50.7 (38.6, 62.8)	30.6 (19.6, 43.7)	49.5 (39.9, 59.2)	37.8 (28.2, 48.1)	50.5 (43.1, 58.0)	36.0 (28.9, 43.7)
Average Symptom Burden Index, time to deterioration HR (95% CI)	0.60 (0.30, 1.22)		0.49 (0.27, 0.88)		0.74 (0.49, 1.12)
Total Score Lung Cancer Symptom Scale, time to deterioration HR (95% CI)	0.89 (0.45, 1.78)		0.71 (0.41, 1.23)		0.90 (0.60, 1.36)
SAFETY POPULATION	Ramucirumab+Docetaxel N = 70	Placebo+Docetaxel N = 61	Ramucirumab+Docetaxel N = 109	Placebo+Docetaxel N = 97	Ramucirumab+Docetaxel N = 179	Placebo+Docetaxel N = 171
Any Treatment-Emergent Adverse Event (TEAE), n (%)	67 (95.7)	58 (95.1)	105 (96.3)	92 (94.8)	173 (96.6)	159 (93.0)
Grade ≥3	50 (71.4)	46 (75.4)	80 (73.4)	69 (71.1)	134 (74.9)	113 (66.1)
TEAE leading to discontinuation	4 (5.7)	2 (3.3)	5 (4.6)	3 (3.1)	13 (7.3)	6 (3.5)
TEAE leading to dose adjustment	24 (34.3)	19 (31.1)	39 (35.8)	28 (28.9)	70 (39.1)	47 (27.5)
TEAE leading to death	5 (7.1)	4 (6.6)	7 (6.4)	6 (6.2)	9 (5.0)	8 (4.7)
TESAE	25 (35.7)	30 (49.2)	46 (42.2)	46 (47.4)	80 (44.7)	71 (41.5)

Conclusion:
Efficacy, toxicity, and QoL outcomes among ramucirumab+docetaxel patients who have aggressive disease with rapid TTP on 1L therapy appear consistent with the intent-to-treat population. The benefit/risk profile for these rapid progressors suggests that such patients may derive meaningful benefit from ramucirumab+docetaxel in the 2L setting.

Background:
Background: INF-γ had recently been known to take part in cancer immunology and its interactions with chemotherapy were also described. Our previous study had showed that impaired PHA-stimulated INF-γ (PSIG) response from peripheral lymphocytes was associated with lower one-year overall survival in advanced non-small cell lung cancer (NSCLC) patients. In this study, we aimed to evaluate the correlation between PSIG and chemotherapy response.

Method:
Form January 2011 to August 2012, 340 newly-diagnosed lung cancer patients from 4 referral centers in Taiwan were enrolled in a prospective latent TB observational study. Patients who had advanced NSCLC and had been treated with chemotherapy were included in this study. The pretreatment PSIG levels were evaluated by Interferon-Gamma Release Assay (IGRA) with QuantiFERON-TB In-Tube (Qiagen, Germany). Patients were grouped into high PHA response group if their PSIG levels were above the median level; the others were grouped into low PHA response group. Their demographic characteristics, tumor response, and survival were investigated and correlated with PSIG levels.

Result:
Eighty-four patients were enrolled in this study. The response rate in high PHA response group was 45.2%, versus 35.7% in lower PHA response group (p=0.999190). The disease control rate in high PHA response group was 76.2%, versus 52.4% in low PHA response group (p=0. 023999). In multivariate analysis, PSIG response was an independent predictor for disease control rate (OR=3.017, 95% CI= 1.115-8.165). Also, the Kaplan-Meier curves and estimates survival analysis demonstrated both longer progression-free survival (p=0.008) and overall survival (p=0.003) in high PHA response group.

Conclusion:
Higher pre-treatment PSIG response, assayed by IGRA testing, was associated with better disease control rate and survival among advanced NSCLC patients treated with chemotherapy.

Abstract not provided

Background:
The U.S. Food and Drug Administration approved pembrolizumab in combination with carboplatin/pemetrexed for patients with untreated, metastatic, non-squamous, non-small cell lung cancer based on KEYNOTE 021G. This trial randomized 123 patients to carboplatin/pemetrexed versus carboplatin/pemetrexed/pembrolizumab with maintenance pembrolizumab. Maintenance pemetrexed was optional in both arms. Progression-free survival (PFS) was longer for carboplatin/pemetrexed/pembrolizumab (not reached vs. 8.9 months, HR 0.49, 95% CI 0.29-0.83, p=0.0035). No statistically significant improvement in overall survival (OS) has yet been demonstrated (HR 0.69, 95% CI 0.36-1.31, p=0.13), with neither arm reaching median OS. Frontline pembrolizumab improves PFS and OS in comparison to chemotherapy in patients with high PD-L1 expression. Drug cost information should be available to providers to better inform decision-making and assess value.

Method:
Dose calculations were based on the following: GFR 125, BSA 2.00 m2, carboplatin AUC 5, pemetrexed 500mg/m2, and pembrolizumab 200mg. Drug costs were obtained via the Centers for Medicare & Medicaid Services Pricing File.

Result:
Four cycles of carboplatin/pemetrexed/pembrolizumab followed by maintenance pembrolizumab and pemetrexed cost $618,889. Four cycles of carboplatin/pemetrexed followed by pemetrexed maintenance cost $249,972. Pembrolizumab alone for an equivalent number of cycles cost $368,917. Table 1: Regimen Cost Calculations Figure 1



Conclusion:
While the addition of pembrolizumab to front-line therapy resulted in an improvement in PFS in a phase II study of 123 patients, it increased medication costs 2.4 fold, from $249,972 to $618,889. Phase III trials are underway to more definitively assess the benefit of immunotherapy administered with chemotherapy in a broad population of patients. Treatment with carboplatin/pemetrexed/pembrolizumab cost 1.7 times that of pembrolizumab alone, and the addition of chemotherapy is of unclear benefit for patients with high PD-L1 expression. Further defining patient subsets who will benefit the most from this costly regimen should be undertaken. It is crucial healthcare professionals and patients understand the cost implications of front line therapy options.

Background:
Emergence of new active drugs and improvement in supportive care make it more likely for patients with advanced NSCLC to receive a fourth-line therapy.However, no survival benefit of such treatment has ever been demonstrated yet, although some studies suggest that it may be effective in selected patients. A better selection could avoid exposing patients to futile and toxic treatments. We conducted a study aiming at identifying prognostic factors in patients with advanced NSCLC treated with a fourth-line therapy.

Method:
In this retrospective, multicentric study, patients with advanced NSCLC receiving a fourth-line therapy were included. Factors associated with prolonged overall survival (OS, defined as OS >6 months) were identified by univariate and multivariate analysis using a Forward method.

Result:
151 patients were included in this study between Jan 2015 and Dec 2016. Median age was 60 (range 55-64). Most patients were male (70%) and had adenocarcinoma (72%). Most common prior treatments included platinum-based chemotherapy (92%), single-agent chemotherapy (81%), targeted therapies (46%) and immunotherapy (9%). Median OS was 7.39 months (6.7-9.43). Nine factors were significantly associated with OS >6 months: current smoker (Hazard Ratio (HR) 1.99, 95% confidence interval[1.16-3.41]), former smoker (HR 0.51[0.30-0.98]), Karnofsky Index (KI) ≥ 90% at the start of fourth-line therapy (HR 0.35[0.19-0.65]), weight loss since first-line therapy (HR 1.85[1.06-3.23]), early stage at diagnosis (HR 0.48[0.24-0.96]), number of cycles and delay since first-line therapy (HR 0.94[0,89-0,99]and 0.99[0.99-1]), Progressive Disease (PD) as Best Objective Response (BOR) in the first 3 lines of treatment (HR 2.92[1.9-5.37]), absence of grade ≥ 3 Adverse Events (AEs) during first-line therapy(HR 0.54[0.31-0.94]). Among them, 4 independent variables were found to be statistically significant by multivariate analysis, including early stage at diagnosis (HR 0.37[0.16-0.58]), absence of grade ≥ 3 AEs during first-line therapy (HR 0.56[0.32-0.98]), PD as BOR in the first 3 lines of treatment (HR 3.06[1.64 -5.73]) and KI ≥ 90% at the start of fourth-line therapy (HR 0.31[0.16-0.58]).

Conclusion:
We highlighted 4 factors significantly associated with OS >6 months in patients treated with fourth-line advanced NSCLC. These factors need to be prospectively assessed to confirm if they could help identifying patients who may benefit from fourth-line therapy.

Background:
Lung cancer is the leading cause of cancer-related mortality worldwide with a 5 year survival rate of 15%. Non-small cell lung cancer (NSCLC) is the most commonly diagnosed form of lung cancer. Cisplatin-based regimens are currently the most effective chemotherapy for NSCLC, however, chemoresistance poses a major therapeutic problem. New and reliable strategies are required to avoid drug resistance in NSCLC. Cell division cycle associated 3 (CDCA3) is a key regulator of the cell cycle. CDCA3 modulates this process by enabling cell entry into mitosis through degradation of the mitosis-inhibitory factor WEE1. Herein, we describe CDCA3 as a novel prognostic target to delay or prevent cisplatin resistance in NSCLC.

Method:
CDCA3 expression was investigated using bioinformatic analysis, tissue microarray immunohistochemistry and western blot analysis of matched NSCLC tumour and normal tissue. CDCA3 function in NSCLC was determined using several in vitro assays by siRNA depleting CDCA3 in a panel of three immortalized bronchial epithelial cell lines (HBEC) and seven NSCLC cell lines. To determine strategies to suppress CDCA3 activity the phosphorylation status of CDCA3 was assessed using mass spectrometry analysis. Kinases that phosphorylate CDCA3 were identified using a siRNA screen and high content immunofluorescence and microscopy approaches.

Result:
We have previously shown that CDCA3 transcripts and protein levels are elevated in resected NSCLC patient tissue, high mRNA levels being associated with poor survival. CDCA3 depletion markedly impairs proliferation in seven NSCLC cell lines by inducing a G2 cell cycle arrest. Silencing of CDCA3 also greatly sensitises NSCLC cell lines to cisplatin. Consistently, NSCLC patients with elevated CDCA3 levels and treated with cisplatin have a poorer outcome than patients with reduced CDCA3 levels. To aid patient response to cisplatin, we have been looking at strategies to suppress CDCA3 expression in tumour cells. Accordingly, in response to cisplatin, CDCA3 is phosphorylated (S[222]) via casein kinase 2 (CK2) which prevents CDCA3 degradation in NSCLC cells. Moreover, the CK2 inhibitor CX-4945 reduces CDCA3 levels in cisplatin treated cells. CX-4945 increased cisplatin-induced cell death in control cells. The efficacy was further enhanced in CDCA3 depleted NSCLC cells.

Conclusion:
Our data highlight CDCA3 as a novel factor in the pathogenesis of NSCLC. We propose that preventing cisplatin-induced CDCA3 phosphorylation by targeting CK2 is a worthwhile and novel strategy in treating NSCLC and may ultimately benefit patient outcome by preventing cisplatin resistance.

Abstract not provided

Background:
Coordinated multidisciplinary (MD) lung cancer care, with all key specialists concurrently providing early input to develop a consensus care plan in collaboration with patients and their caregivers, may improve patient-centered outcomes over the usual serial care (SC) model, but needs rigorous evaluation.

Method:
Prospective, longitudinal study comparing newly-diagnosed lung cancer patients receiving MD vs. SC within the same US healthcare system. The MD intervention was implemented from lung cancer care initiation until definitive treatment decision. After that, both cohorts of patients received their actual cancer treatments within the same environments. At baseline and 6 months, patients completed treatment-related satisfaction measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) and the Functional Assessment of Cancer Therapy- Lung (FACT-L) quality of life instrument. All measures were coded so that larger scores are better. Time-specific comparisons were made with the Wilcoxon-Mann-Whitney test and changes from baseline to 6 months were compared between MD vs. SC patients in mixed linear models.

Result:
The 463 patients who participated (156 MD, 307 SC) were similar in sex and health insurance. MD cohort was slightly older (69 v 66 years), with more racial minorities (37% v 29%). Patients receiving MD care reported greater satisfaction with the treatment plan (p=0.0266) and overall quality of care (p<0.0010) at 6 months. Additionally, satisfaction with the treatment plan showed greater improvement over time for MD vs. SC (p-value for trend=0.0046). SC patients showed more improvement in satisfaction with overall care than MD patients, but did not reach the level of satisfaction of MD patients at 6 months (p-value for trend=0.0018). Caregivers of MD patients perceived receiving better quality of care compared to other lung cancer patients than caregivers of SC patients (p=0.0049). Caregiver satisfaction did not differ between MD and SC in the communication measures or overall quality, and did not have significant differences in the trend over time. Patient reported Health-Related Quality of Life (HRQOL) improved from baseline to 6 months for the lung cancer-specific scale compared with no change with SC (p-value for trend= 0.0334). Other HRQOL scales were similar between groups

Conclusion:
Compared with SC patients, MD patients experienced improved lung cancer-specific HRQOL and greater satisfaction with both treatment plan and quality of care received. MD patients’ caregivers were more likely than SC patients’ caregivers to think their care was better than that of other patients.

Background:
The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire and the Canadian Problem Checklist (CPC) are validated screening tools used to identify the psychosocial needs of patients with cancer. The questionnaire identifies at-risk patients requiring timely psychosocial intervention and the CPC comprises of patient-reported support needs in 6 psychosocial domains. The study goal was to review reported needs of patients with NSCLC to facilitate the development of programs and resources specific to those identified as at-risk for psychosocial distress.

Method:
All patients with NSCLC referred to BC Cancer Agency centres from 2011-2015, who completed a prospective PSSCAN-R and CPC questionnaire at the time of their first visit, were included in the study. Demographics and baseline disease characteristics were collected retrospectively. Univariate analysis using the Chi-squared test and Fisher’s exact test were used to compare patient groups based on gender, age and stage of disease.

Result:
4313 patients completed the PSSCAN-R and CPC questionnaire. The median age was 70 (21-99), with 50% female and 51% of patients with stage IV disease. 29% of patients live alone with 13% having lost their spouse/partner. However, 93% of patients report regular contact with friends/relatives and 85% have someone who can provide assistance with daily tasks (shopping, cooking, transportation). Female patients, patients aged 65 or younger, and those with advanced disease were more likely to report significantly higher levels of anxiety and depression, and reported higher number of needs on the CPC. Figure 1



Conclusion:
Newly diagnosed patients with NSCLC report clinically higher levels of anxiety and depression and have greater number of concerns in multiple psychosocial domains. Resources should be developed for lung cancer patients based on their care needs with careful consideration of patients' age, gender and disease stage to optimally support their psychosocial needs during treatment and follow up.

Abstract not provided

Background:
The Mesothelioma Applied Research Foundation is the nonprofit collaboration of patients and families, physicians, advocates, and researchers dedicated to eradicating the life-ending and vicious effects of mesothelioma. The Meso Foundation’s Advocacy Program objective is to obtain federal funding for mesothelioma research.

Method:
An analysis was performed of the Meso Foundation’s advocacy efforts and grant funding from years 2000- 2015.

Result:
The Meso Foundation has funded 103 projects from 8 countries for a total awarded amount of 9.8 million dollars. From 2000- 2015, the Meso Foundation grant program has funded research that has produced over 240 publications in peer reviewed journals. As a direct result of Foundation advocacy, the Department of Defense has awarded a total of $12.4 million to mesothelioma research since 2008. The Meso Foundation’s grant program has funded the basic science research that helped lay the groundwork for several mesothelioma clinical trials. A few of the more notable trials include the measles virus and the WTI Vaccine. Several of the proposals funded by Meso Foundation grants have extended to global levels through presentations at international conferences including but not limited to International Association for the Study of Lung Cancer (IASLC), American Society of Clinical Oncology (ASCO), and American Association for Cancer Research (AACR).

Conclusion:
Through actively engaging members of congress, the Meso Foundation has successfully advocated for increased funding for mesothelioma research. The Meso Foundation is committed to leveraging the knowledge we gain from our own research, as well as discoveries made by our collaborations with academic institutions and industry partners to work toward the development of innovative treatments and care platforms for mesothelioma patients and their families.

Background:
When captured by psychometrically-sound patient-reported outcomes measures (PROMs), patients’ appraisals of their symptoms, quality of life and functional status can provide powerful data to better inform clinicians about the impact of health conditions and the consequences of medical care. Reviewing and reporting on integrated PROMs alongside clinical data may translate to health service improvements and efficiencies. There are, however, many challenges including the need to find sustainable and cost-efficient methods for the routine collection of PROMs across the whole patient journey. This two-phase study set out to develop a lung cancer clinical quality registry framework to collect longitudinal patient-reported outcome measures. Phase 1 focused on the development of the data collection framework and phase 2 sees a 12-month implementation and mixed-method evaluation of the feasibility of implementing the framework. We will report on development of the framework and provide preliminary results on the implementation phase.

Method:
The development phase utilised a formative evaluation method to decide on essential aspects of the PROMs framework. Specifically, a Delphi process was employed to seek consensus on PROMs to administer and the schedule of assessments, with a specific focus on clinical relevance and feasibility of administration. The first Delphi round consisted of individual interviews with lung cancer clinical experts to generate a list of domains to be included in the PROMs. In the second round, aggregated results were presented to the panel and domains of interest were considered alongside PROMs meeting minimum measurement standards. Then, four patients previously treated for lung cancer were invited to provide feedback on the content of PROMs and data collection methods.

Result:
From Delphi findings, it was determined that the EORTC QLQ-C30 and the lung cancer-specific module (QLQ LC13) would be administered at baseline and two, six and 12 months after baseline, and a brief social isolation measure (PROMIS) would be administered at baseline only. A clearly defined subset of patients about to commence chemo-radiation treatment for lung cancer was chosen for the implementation phase and commenced on October 31 2016. To date, 74% (14/19) of eligible patients have been recruited thus far. Preliminary data indicate high adherence to baseline assessments (100%). Adherence is much lower at two months (50%), with non-adherence frequently due to side effects or ill health (38%).

Conclusion:
Identifying and deciding which PROMs to collect, the overall purpose of PROMs collection, data completeness and utility requires careful consideration and evaluation to determine framework sustainability.

Background:
Despite evidence that lung cancer disproportionately affects minority populations, there is a paucity of data describing the impact of lung cancer screening. Results of NLST may not be generalizable to all populations given that 91% of the participants were Caucasians. Further study of lung cancer screening in a diversity of racial and ethnic groups is a necessary step in the implementation of lung cancer screening. Before underrepresented populations can be screened, community perceptions about lung cancer screening must be explored and barriers to screening must be identified. The purpose of our study was to identify potentially correctable barriers to obtaining LDCT for lung cancer screening in a diverse, but predominantly African American population.

Method:
We developed a questionnaire consisting of 22 items. Five questions assessed patient demographics including socioeconomic status and insurance coverage. Two questions assessed patient access and utilization of health care. Three questions assessed smoking history and prevalence in interpersonal relationships. One questions assessed patient concern about lung cancer. Two questions measured patient knowledge about lung cancer. One question addressed patient willingness to go to a doctor’s appointment to learn more about lung cancer screening. One question elicited whether LDCT had been mentioned by a healthcare provider. Six questions assessed awareness and knowledge about LDCT lung cancer screening. One question addressed reasons for non-adherence to appointments.

Result:
The questionnare was complete by 100 patients. Almost all of our patients reported having health insurance and a primary care doctor (96%). 50% of patients are current or former smokers. 83% are current or former smokers or have friends and/or family members who are heavy/long time smokers. 90% of patients knew that smoking is the most common cause of lung cancer. 56% of patients know that lung cancer can be treated successfully at least sometimes. 81% of patients reported to be at least somewhat concerned that they or someone they know can die of lung cancer. 87% of patients are willing to go to a doctor’s appointment to learn more about lung cancer screening. 100 % of patients reported to have not heard about LDCT from their doctors. The average score was 2/6 (33%) on items accessing knowledge about lung cancer screening. Cost was the most frequently reported reason (52%) for nonadherence to appointments.

Conclusion:
Our study was able to identify potentially correctable barriers to utilization of low dose CT lung cancer screening such a lack of primary care support and perceived cost.

Abstract not provided

Background:
Japan’s measures to prevent passive smoking are considered to be among the world’s worst. Creating smoke-free environments is an urgent task for Japan as it prepares to host the 2020 Tokyo Olympics and Paralympics Games. In spring of 2017, discussions on a draft bill to strengthen measures against passive smoking were stalled due to opposition from within the ruling party. One lawmaker remarked that “(Cancer patients) don’t have to work”, indicating that patients can choose their occupation and avoid secondhand smoke as they wish. Against this backdrop, the Japan Lung Cancer Alliance conducted a survey on damage by secondhand smoke to cancer patients. Based on the survey’ result, this study aims to shed light on the problems experienced by lung cancer patients including the impact of secondhand smoke on their employment.

Method:
For 5 days from 28 May to 1 June 2017, a survey by questionnaires was conducted on lung cancer patients. The announcement of the survey was made by ten patient advocacy groups.

Result:
There were 231 responses, among which valid responses were 215. 91 percent of the respondents considered passive smoking “unpleasant” due to fears or anxieties for recurrence of lung cancer and/or hatred. It was found that among those respondents who were employed at the time of the survey, about 31 percent had been exposed to secondhand smoke at their workplace, and 4.2 percent had quitted their job. Not only at the work place, 6.2 percent of the respondents were exposed to the secondhand smoke at home, event after they were diagnosed as lung cancer.

Conclusion:
It is understood that working cancer patients worry about recurrence of cancer and/or hatred. Moreover, the experiences of those lung cancer patients who had left their job because of passive smoking reveal a lack of the freedom to choose their occupation. The urgent countermeasure is also required to prevent the passive smoking at home. Japan’s delay in adopting measures against passive smoking appears be related to an insufficient level of understanding in the society about difficulties faced by cancer patients. It is hoped that this study will draw attention to the damage by passive smoking to lung cancer patients and foster international support for the advocacy of legislation enacting stricter measures.

Background:
The rising imperative to improve our understanding of cancer heterogeneity and individualised drug response has led to a high demand for biopsy material. With improvements in technologies, there is now a move away from more traditional tissue based sampling to liquid based biopsies. ‘Liquid biopsies’ provide a non-invasive means for molecularly profiling patients with cancer, thus benefiting patients and clinicians in terms of treatment choice and shared decision-making. We assessed the willingness of patients to undergo repeated tissue and/or ‘liquid’ based sampling.

Method:
Detailed questionnaires, assessing patients’ perceptions of, and willingness to undergo serial biopsies were distributed to ambulatory patients at a tertiary cancer referral centre (St. James’s Hospital, Dublin). Multivariate analysis was performed using ordinal logistic regression analysis.

Result:
The questionnaire response rate was 97% (247/255). Respondents were primarily female (73%), aged between 51-70 yrs (51%), with breast (39%), colorectal (16%), oesophagogastric (13%), and lung cancer (12%). Of those that responded, repeat biopsy of an easily accessible lesion was acceptable to 203 (82%) patients if recommended by an oncologist. However this reduced to 102 (41%) patients, if the purpose was solely for clinical trial. Acceptability decreased to 168 (68%) and 81 (33%) patients respectively for more invasive biopsies. Additionally, 79 (32%) patients were willing to undergo additional biopsy for research purposes only, with 54 (21%) patients uncertain of its utility in research. Lower performance status (OR=0.44, p=0.04) and the belief that biopsy was unimportant for research (OR=0.74, p=0.04) negatively impacted on willingness to undergo biopsy, while a prior invasive biopsy increased acceptance (OR=1.02, p=0.02). In terms of blood sampling, 82% of patients would consent to repeated blood sampling over the course of their treatment, with >5 samples considered acceptable by 51.5% of patients. Patients with lung cancer had 3.38 greater odds (OR=3.38, p=0.047) of consenting to a repeated blood sample for purely research purposes (compared to any other type of cancer); however their willingness to undergo repeat biopsy was similar to that of other patients (OR=1.99, p=0.129). Data analysis is currently on-going.

Conclusion:
Patients with cancer are willing to participate in serial sampling of blood and urine but are less likely to consent to repeated tissue biopsies. Patients with lung cancer were particularly amenable to repeated blood sampling compared to patients with other cancer types. This is significant given the recent data supporting the use of ‘liquid’ biopsy for real-time monitoring of resistance mutations and treatment response dynamics in patients with lung cancer.

Background:
Lung cancer stigma has wide-reaching effects and impacts treatment, quality of life, survival, societal attitudes, research funding, and advocacy efforts. Those affected by lung cancer commonly feel hopeless, isolated, reluctant to share their diagnosis in addition to feelings of guilt, shame, anxiety and depression. Stigma responses can hinder information seeking information related to treatment options and psychosocial support and, tragically, can cause delays in diagnosis and even refusal of treatment. Major pan-cancer organizations, those dedicated to all lung diseases as well as lung cancer-specific organizations conduct awareness raising campaigns designed to confront lung cancer stigma, all working in some measure to create a more compassionate and empathic environment for those at-risk and diagnosed. These efforts have not been coordinated and to date, no known comprehensive vision to address lung cancer stigma in its entirety has been developed.

Method:
HIV/AIDS and mental health advocates have devoted extensive efforts to developing coordinated stigma reduction plans. While not always applicable, their approaches can inform our efforts in lung cancer. To develop a comprehensive framework to address lung cancer stigma, a synthesis of relevant strategies used in other disease-states, a review of lung cancer stigma literature and exploration of the efforts of organizations and individuals from around the world was conducted.

Result:
Awareness-raising, myth-busting and public health advocacy are featured prominently in other stigma-reduction plans. Lung cancer, like HIV/AIDS and other smoking-related cancers, must also address nihilism from medical professionals and work to ensure non-judgmental discussions and compassionate treatment environments that explore appropriate treatment options become the norm. Founded on seven key areas of opportunity, the plan includes multiple areas of impact that need to be addressed. Included are suggested remediation methods and real-world examples from all over the globe to illustrate creative ways lung cancer stigma reduction can be approached. This comprehensive, multi-level, multi-pronged vision allows individuals, systems and organizations to find points of convergence and work collaboratively on addressing the stigma so closely associated with lung cancer.

Conclusion:
Through a comprehensive approach, lung cancer stigma can be reduced and ultimately eliminated. To initiate a global conversation and better unite the lung cancer community, we offer this unifying strategy to address lung cancer stigma. Through the menu of stigma-reduction strategies, we hope to spark conversation, collaboration, and convergence. Dedicated medical professionals, survivors, loved ones, advocacy organizations and others can use the vision to apply appropriate strategies in their regions/countries and work collaboratively toward this all-important goal.

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Abstract:
The Holy Grail of precision medicine is the comprehensive integration of patient genotypic with phenotypic data to develop personalized disease prevention and treatment strategies. Single cell sequencing, single cell mass cytometry (CyTOF), microbiome, and other types of high-throughput assays have exploded in popularity in recent years. The ability to generate big data brings us one step closer to the realization of precision medicine; nevertheless, across the life cycle of such data, from experimental design to data capture, management, analysis, and utilization, many challenges remain. In this session, I will discuss the artificial intelligence in cancer research, common statistical and bioinformatic mistakes for designing, analyzing, and interpreting the Omics based biomarker research. I will also discuss potential pathways for the seamless integration of cellular and molecular data with clinical, behavioral, and environmental parameters – a critical next step in advancing the goals of precision medicine.

Abstract:
Despite advances in immunotherapy and targeted therapies for lung cancer, cytotoxic chemotherapeutic agents remain the backbone of therapy for most patients. There has long been evidence that different populations demonstrate differential sensitivity and toxicity to chemotherapy agents. With the increasing globalization of trials, understanding and adjusting for these differences will be of increasing importance for the development of new agents as well as the safe and effective use of existing drugs. Mechanisms of differential toxicity/efficacy Different populations may experience altered safety profiles. Differential toxicity is not surprising as different populations demonstrate variability in detoxifying liver enzymes (e.g.cytochrome P450). Depending upon the drug, this could alter metabolism to an active agent or to an inactive compound. Metabolism can also affect aspects of drug clearance. Differential efficacy could be the result of several factors. Altered metabolism or clearance (as discussed above) may result in greater exposure of the tumor to active agent. Alternatively, accelerated metabolism/clearance could result in less exposure and potentially less activity. Another, less well appreciated aspect, is the different incidence of activating mutations in the populations, such as EGFR or ALK. Dietary differences may also alter metabolism and activity. Some of this is due to regulatory requirements. For example, the United States requires folate supplementation of bread and many other products to prevent congenital neural tube defects. This is not required in the European Union. Pemetrexed toxicity is significantly impacted by folate repletion and as early development in the EU demonstrated that additional folate obviated rash and led to the requirement for folate supplementation. It is possible that this has resulted in over supplementation in the US. Conversely, capecitabine becomes more toxic (and possibly more effective) in folate replete patients. Trial evidence for differential toxicity/efficacy Observed differences in efficacy could potentially be due to differences in entry criteria, study execution etc. Investigators in the United States (Southwest Oncology Group, SWOG) and Japan addressed these issues through a series of “common arm” trials in small cell (SCLC) and non-small cell lung cancer (NSCLC). Trials comparing cisplatin/etoposide with cisplatin/irinotecan were conducted in Japan (J9511) and the United States (S0124). A retrospective analysis of patient level data was undertaken. Drug doses, eligibility criteria, assessments and analysis were similar between the two studies. There were significant differences in toxicity and efficacy. Both cisplatin/etoposide and cisplatin/irinotecan demonstrated greater hematologic toxicity in the Japanese. In terms of efficacy, cisplatin/etoposide demonstrated higher response rate, but similar survival endpoints. In contrast, cisplatin/irinotecan demonstrated a higher response rate, progression free and overall survival in the Japanese vs. US population. An analysis of the US trial demonstrated significant associations of GI and hematologic toxicity with ABCB1 (Odds Ratio, OR: 3.9) and UGT1A1 (OR: 24) polymorphisms, respectively. A prospective “common arm” study was undertaken in the NSCLC setting by the same groups. In this case, the common arm was carboplatin/paclitaxel. Once again there were significant differences in terms of both toxicity and activity. In this prospective study, the investigators obtained information regarding germline CYP and DNA repair enzymes. There were significant differences between patients from Japan and the USA in genotype distribution for CYP3A4*1B (p = 0.01), CYP3A5*3C (p = 0.03), ERCC1 118 (p < 0.0001), ERCC2 K751Q (p < 0.001) and CYPC28*3 (p = 0.01). Mutational status may influence response to chemotherapy and there are clear geographic variations for some driver mutations. The incidence of activating mutations of EGFR is approximately 10% in Western countries but >25% in many Asian countries. In addition to predicting outcome for EGFR tyrosine kinase inhibitors (TKIs), EGFR mutations also convey greater sensitivity to cytotoxic chemotherapy. In the IPASS study, the response rate for carboplatin/paclitaxel was 47% vs. 23.5% for mutation positive vs. negative patients. Given the much greater number of patients with EGFR mutation related NSCLC in Asia, this is likely a major source of discrepancy in outcomes. Interestingly, mutational status may also influence the degree of benefit from different chemotherapy agents. In a phase III trial comparing chemotherapy to crizotinib in patients with ALK translocated disease, patients could receive either pemetrexed or docetaxel as their chemotherapy. The HR for crizotinib vs pemetrexed was .59 while it was .30 for patients receiving docetaxel. Summary The past 20 years has seen significant progress in our understanding of lung cancer. It is now common to declare that there are many different lung cancers and to focus on susceptibility to targeted or immunotherapy based upon tumor characteristics. It is critical that in this era we not lose sight of the fact that there is still significant potential to improve outcomes with older chemotherapy agents, both in terms of toxicity and efficacy, based upon better understanding and utilization of both germline and tumor characteristics. Insights gained from evaluations of different ethnic groups can guide these evaluations. Suggested Reading Edelman MJ, Sekine I, Tamura T, Saijo N. Geographic variation in the second-line treatment of non-small cell lung cancer. Semin Oncol. 2006 Feb;33(1 Suppl 1):S39-44 Gandara DR, Kawaguchi T, Crowley J, Moon J, Furuse K, Kawahara M, Teramukai S, Ohe Y, Kubota K, Williamson SK, Gautschi O, Lenz HJ, McLeod HL, Lara PN Jr, Coltman CA Jr, Fukuoka M, Saijo N, Fukushima M, Mack PC. Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics. J Clin Oncol. 2009 Jul 20;27(21):3540-6. Lara PN Jr, Chansky K, Shibata T, Fukuda H, Tamura T, Crowley J, Redman MW, Natale R, Saijo N, Gandara DR. Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer: final patient-level results from Japan Clinical Oncology Group 9511 and Southwest Oncology Group 0124.Cancer. 2010 Dec 15;116(24):5710-5. Mack PC, Gandara DR, Lara PN. Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the ‘common arm’ approach Expert Rev. Anticancer Ther. 12(12), 1591–1596 (2012) Mok TS1, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Saijo N. The Role of Pharmacoethnicity in the Development of Cytotoxic and Molecular Targeted Drugs in Oncology Yonsei Med J 5: 1-14, 2013 Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94.

Abstract:
It has been recognized that ethnic differences contribute to disparities in carcinogenesis and treatment outcomes in lung cancer. The disparities can be due to the variety of mutations which are developed and triggered by the evolutionary forces over time and across populations. Although several single nucleotide polymorphisms as genome-wide significant signals can be associated with the mutations, environmental factors including smoking, dust exposures, obesity and potential viral infections (human papilloma virus) are also essential to the genomic diversity. Frequent occurrence of EGFR mutations is likely to be a feature of lung adenocarcinoma in Asian female never smokers including Japanese, while KRAS mutations are more common in Caucasian smokers. Because Japanese women are likely to have more environmental tobacco smoke (ETS) exposure, we conducted a single-center prospective study to examine an association between ETS and EGFR mutations in never smokers with non-small cell lung cancer (NSCLC) and clarify the reason for the unique background. We showed the development of EGFR mutations was inversely proportional to the dose of ETS exposure in never-smokers.[1] However, there are conflicting data published regarding the relationship, and mystery of the mutation still deepens. Based on recent developments in next-generation sequencing techniques detecting many genetic alterations, the Japan Molecular Epidemiology for lung cancer (JME) study has been designed and conducted beyond the scope of EGFR and KRAS mutations.[2] The aim of this prospective, multicenter, molecular epidemiology study is to elucidate the relationship between tumor developmental biology and exposure to environmental factors. A total of 876 surgical samples from 441 ever- and 435 never-smokers with early stage NSCLC underwent molecular analyses. In smokers, the most frequent mutations were TP53 (38%), EGFR (20%), KRAS (13%), NFE2L2 (6%) and PIK3CA (4%), whereas in never-smokers, EGFR (61%), TP53 (15%), KRAS (4%) and PIK3CA (2%) were the most frequent. Dominant base substitutions were C>A transversion and C>T transition in TP53, C>A transversion in KRAS, C>G transversion in NFE2L2 and C>T transition in PIK3CA. Mutations in P53 and KRAS increased proportionally with smoking status, while EGFR mutations decreased. KRAS mutations in smokers were more frequently observed in proportion to body mass index. As for the ethnic difference on these mutations, our data can be compared with another integrative genomic analysis from The Cancer Genome Atlas (TCGA).[3,4 ]The study population in the TCGA was mostly Caucasian smokers with mixed smoking dose in early stage NSCLC, while the JME study was exclusively in Japanese patients, half of which were smokers and the other half never-smokers in the similar stage. In adenocarcinoma, the frequency of EGFR mutations was inversely proportional to the degree of smoking exposure both in the US and Japan. The mutation rates were always higher in Japan than in the US in each smoking status. While in KRAS and TP53 mutations, the frequencies increased proportionally as smoking; however, the mutation rates were always higher in the US than in Japan. The mutation rates of KEAP1, NF1 and STK11 seemed to be higher in the US than in Japan, regardless of smoking status (Table). In squamous cell carcinoma, KEAP1 and NF1 were also lower in Japan as well as TP53. The difference in ethnicity and potentially unveiled environmental factors can explain differences in the mutations prevalence. Figure 1 From the beginning, the JME study has been designed to investigate the relationship between ethnicity and NSCLC carcinogenesis. Our potential counterpart study is S0424 which is a molecular epidemiological study in the US by using a detailed questionnaire and NSCLC tissue specimens from smoker and never-smoker men and women with early stage NSCLC. The JME study follows and extends the concept of S0424 by using a similar questionnaire that will allow us for direct comparison of data. We believe that the real value of genomic data will be realized only when they are linked to high-quality and solid clinical information, allowing us to identify precise genotype–phenotype associations. In conclusion, ethnicity is an important and complex characteristic that needs to be recognized and considered even in the era of precision medicine. We should collaborate to share the data from different ethnicity and translate them into the clinical practice and the design of a global clinical study. Carefully designed molecular epidemiological studies focused on ethnic differences are warranted. Reference 1. Kawaguchi T, Ando M, Kubo A, et al. Long exposure of environmental tobacco smoke associated with activating EGFR mutations in never-smokers with non-small cell lung cancer. Clinical cancer research 2011;17:39-45. 2. Kawaguchi T, Koh Y, Ando M, et al. Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study. Journal of clinical oncology 2016;34:2247-57. 3. Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-50. 4. Cancer Genome Atlas Research N. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489:519-25.

Abstract:
By sequencing lung cancers via an unbiased approach, The Cancer Genomic Atlas (TCGA) and similar analyses have elucidated commonly altered pathways and the molecular heterogeneity that underlies this disease. Data from these studies have shown that mutations in TP53, RB1, and MYC family amplifications are frequently associated with small cell lung cancer, while alterations in RTK/RAS/RAF pathway genes such as KRAS, EGFR, ALK, BRAF, and ROS1, and alterations in genes regulating squamous differentiation are frequently found in adenocarcinomas (LUAD) and squamous cell lung cancers (LUSC) respectively [1-8]. Sequencing rare histologies of lung cancer have also provided some insights into the alterations that underlie these diseases. For example, a recent analysis showed that it is possible to segregate large-cell neuroendocrine carcinoma (LCNEC) tumors into SCLC-like or NSCLC-like based on genomic profiling. This study showed that SCLC-like LCNEC tumors were characterized by co-alteration of TP53 and RB1 and/or MYCL amplification, while NSCLC-like LCNEC tumors were characterized by a lack of TP53 and RB1 co-alteration and presence of STK11, KRAS, and KEAP1 alterations [9]. Results such as these emphasize the need for additional efforts to comprehensively study the genetic landscape of rare histologic subtypes of lung cancer to advance our understanding of these subtypes and facilitate the development of novel therapeutic approaches. This is particularly important considering that outcomes with conventional chemotherapeutics remain dismal in patients with these cancers. For many years, events leading to development of cancers such as colon adenocarcinoma have been well catalogued [reviewed in 10], while a thorough understanding of the events leading to the development and progression of lung cancer remains unclear. Defining these events may lead to the development of novel screening and prevention strategies. Recent efforts utilizing next-generation sequencing (NGS) technologies and circulating tumor DNA (ctDNA) assays have facilitated a study of pre-invasive lesions in lung cancer. Apart from cataloguing genomic alterations in pre-invasive lesions, NGS studies have also facilitated the study of the heterogeneity within these lesions. Evaluating this heterogeneity has the potential to reveal the temporal events leading to lung cancer initiation and progression. In one such analysis of precursor lesions in LUAD, sequencing of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) lesions demonstrated frequent mutations in DNA repair genes, with increasing rates of mutations in EGFR and TP53 along the AAH-MIA spectrum, suggesting that serial acquisition of mutations in established driver genes and ongoing genomic instability play an potentially important role in LUAD development. However, in this small study, a single dominant pathway underlying progression from AAH to LUAD was not identifiable [11]. To this end, this study noted significant heterogeneity in mutations depending on the location of sampling suggesting intratumoral heterogeneity even at early developmental stages of LUAD. Using ctDNA, this group could detect mutations that were identified within different regions of the precursor lesions, suggesting that ctDNA may provide an effective method in determining and monitoring molecular heterogeneity in lung cancer development [11]. The Tracking Non-Small Cell Lung Cancer Evolution through Therapy (TRACERx) study was recently conceived to better understand the development and progression of NSCLC. Preliminary results from this multi-center, prospective study, which is still currently accruing patients, revealed that mutations in disease-specific drivers such as KRAS, EGFR, BRAF, and MET, and TP53 were predominantly clonal in both LUAD and LUSC tumors [12]. The study also showed that alterations affecting chromatin remodeling, histone methylation, DNA damage response or repair were subclonal or late alterations in both LUAD and LUSC. While only a preliminary analysis of a much larger planned cohort, results from TRACERx also suggested a positive correlation between increased subclonal copy-number burden and risk of recurrence or death [12]. This correlation was independent of smoking history, histologic subtype, tumor stage, or adjuvant therapy. Taken together with observations in other cancers, these results suggest a role for genomic instability as a prognostic biomarker in lung cancer [13]. Analysis of ctDNA from the same 100 patients enrolled to TRACERx, demonstrated that nearly half (48%) of early-stage NSCLC patients had two detectable SNVs prior to surgical resection. Histologic subtype appeared to be an important factor in ctDNA detection, as ctDNA positivity was seen in only 19% (11/58) of LUAD patients compared with 97% (30/31) in LUSC patients. Clonal SNVs were identified in all ctDNA-positive patients in the study; whereas, only 27/46 (68%) of these patients demonstrated identifiable subclonal SNVs, suggesting that ctDNA analyses may have a higher sensitivity in detecting clonal than subclonal SNVs [14]. In this analysis, reliable detection of ctDNA required an estimated tumor volume of approximately 10 cm[3], which is considerably larger than the 4mm required for detection by low-dose CT [15], leaving the utility of ctDNA monitoring as a screening tool for lung cancer unclear. Longitudinal monitoring of ctDNA using patient-specific ctDNA assay panels, however, could identify patients who eventually relapsed after surgery. This analysis demonstrated subclonal SNVs at a similar allelic frequency to that of clonal SNVs, suggesting that the relapse process in these patients was likely driven by subclones [14]. With the advent of newer sequencing technologies and less invasive methods such as ctDNA monitoring, it is likely that molecular characterization rather than the histopathologic classification of lung cancer alone, will play an increasingly essential role in guiding screening and management strategies. References 1. Network CGAR. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-50. 2. Network CGAR. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489:519-25. 3. Govindan R, Ding L, Griffith M, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 2012;150:1121-34. 4. Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150:1107-20. 5. George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature 2015;524:47-53. 6. Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 2012;44:1111-6. 7. Peifer M, Fernández-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012;44:1104-10. 8. Seo JS, Ju YS, Lee WC, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res 2012;22:2109-19. 9. Rekhtman N, Pietanza MC, Hellmann MD, et al. Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clin Cancer Res 2016;22:3618-3629. 10. Markowitz SD and Bertagnolli MM. Molecular basis of colorectal cancer. NEJM 2009;361:2449-2460. 11. Izumchenko E, Xiaofei C, Brait M, et al. Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. Nat Commun 2015;6:8258. 12. Jamal-Hanjani M, Wilson GA, McGranahan N, et al. Tracking the evolution of non-small-cell lung cancer. NEJM 2017;376:2109-2121. 13. Andor N, Graham TV, Jansen M, et al. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nature Medicine 2016;22:105-113. 14. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature 2017; 545:446–451. 15. Aberle DR, Adams AM, Berg CD, et al. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. NEJM 2011;365:395-409.

Abstract not provided

Abstract:
Is ethnicity a prognostic factor in lung cancer? If so, it is due to differences in tumor genomic characterization, in response to treatment or some other factors? Do patients with different ethnic backgrounds experience different tolerability to therapy? How about culture factors, life style variants or environmental exposures that may pay a role in outcomes? The results from the Lung Cancer Mutation Consortium did not show significant differences in survival between Whites, African Americans, Asians, and Latinos with adenocarcinomas. However, the number of non-Whites in this study was relatively small. The rate of oncogenic mutations was highest among Asians (81%) followed by Latinos (68%), Whites (61%), and African Americans (53%). It is well documented that the frequency of EGFR mutations is higher in Asians (50-60%) than in Whites (10-20%). In fact, based on a case series from a single institution in China, 90% of lung adenocarcinomas from never smokers harbored these oncogenic mutations. Even in Asian current smokers with adenocarcinomas, the frequency of EGFR mutations could be as high as 35.3% as compared to 5.8% in White current smokers with the same histology. It remains unclear why Asians harbor such a high rate of EGFR mutations. A recent meta-analysis of genome-wide association studies of Asian never-smoking women with lung cancer has identified multiple genetic susceptibility loci, which may serve as a plausible explanation. As patients with oncogenic mutations have significantly better outcomes than those without, ethnicity does carry a prognostic value when it comes to Asians vs Whites. In terms of response to treatment, for patients with EGFR mutations, a meta-analysis of 7 randomized trials comparing EGFR tyrosine kinase inhibitors (TKIs) to chemotherapy did not show a clearly better PFS favoring EGFR TKIs for Asians (Hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.31-0.42) than for non-Asians (HR: 0.42, 95% CI: 0.31-0.58). For patients with ALK rearrangements treated with crizotinib versus chemotherapy in PROFILE 1014, a slightly better PFS favoring crizotinib was seen for Asians (157 patients, HR: 0.44, 95% CI: 0.3-0.65) than for non-Asians (186 patients, HR: 0.53, 95% CI: 0.36-0.76), while the opposite was demonstrated with ceritinib in ASCEND-4 (Asians: 158 patients, HR: 0.66, 95% CI: 0.41-1.06; non-Asians: 202 patients, HR: 0.44, 95% CI: 0.3-0.66). In ALEX study, Asians (138 patients, HR: 0.46, 95% CI: 0.28-0.75) had a similar PFS favoring alectinib over crizotinib as non-Asians (165 patients, HR: 0.49, 95% CI: 0.32-0.75). With regards to immunotherapy, no conclusion can be drawn on outcomes between Asians (40 patients, HR: 0.35, 95% CI: 0.14-0.91) and non-Asians (265 patients, HR: 0.52, 95% CI: 0.38-0.72) in KEYNOTE-024 as the study enrolled significantly fewer Asians accounting for the wide range of confidence interval for PFS favoring pembrolizumab over chemotherapy. The discussion on potential differences between Asians and non-Asians in response to chemotherapy is beyond the scope of this mini-review, but it is unlikely that ethnicity would serve as a surrogate factor for efficacy and even tolerability to predict prognosis. Lastly, according to the American Cancer Society, African Americans continue to have higher death rates from lung cancer than Whites, but the gap has narrowed for men. For EGFR mutations, the frequency in African Americans as compared to Whites varied by reports. By using targeted massively parallel sequencing, Araujo et al. have suggested that genomic characterization of African Americans with non-small cell lung cancer (NSCLC) may not be significantly different from that of Whites. However, a pooled analysis done by the same group with a larger sample size has shown a different pattern of oncogenic mutations in African Americans than in Whites, although the frequency of EGFR or KRAS mutations was similar between the two groups. Interestingly, a study utilizing the Veterans Affairs Central Cancer Registry has shown that even though African Americans with NSCLC had worse prognostic factors than Whites, they had a better overall survival. These data suggest that disparity in outcomes between Africans Americans and Whites may be related to barriers to access rather than inherent biology. In summary, ethnicity plays a prognostic role in lung cancer between Asians and non-Asians largely due to the fact that Asians have a higher frequency of oncogenic mutations, which is clearly associated with better outcomes, whereas the disparities between African Americans and Whites are more likely to be driven by healthcare inequality leading to a poorer prognosis among African Americans with lung cancer. Endeavors should be undertaken to provide better access to care for ethnic minorities.

Abstract not provided

Abstract:
The extent of pulmonary resection for peripheral, non-small cell lung cancer (NSCLC) has been defined as "lobe", based on the results of clinical experiences and a randomized trial in 1980's. At present, the possibility of lesser resection such as wedge/segmental resection needs to be evaluated from a updated, scientific viewpoint. For these reasons, JCOG (Japan Clinical Oncology Group) has been prospectively deploying series of clinical trials each for different target lesions to define the proper extent of the parenchymal resection for NSCLC, JCOG 0804, 0802, and 1211. Among these, the most important study is JCOG 0802, in which the non-inferiority of segmentectomy was compared with lobectomy in terms of overall survival for patients with diameter ≤ 2 cm invasive peripheral NSCLC. As a second endpoint, the postoperative pulmonary function was also compared to demonstrate the functional superiority for lesser resection. Between Aug 10, 2009 and Oct 21, 2014, 1,106 patients were enrolled. No mortality was noted. Complications (grade ≥ 2) occurred in 26·2% for lobectomy and 27·4% for segmentectomy. Multivariate analysis indicated a pack-year (PY) smoking >20 (vs. none) as a predictor of postoperative complications (grade ≥ 2), and a complex segmentectomy (vs. lobectomy) and PY > 20 as a predictor of pulmonary complications. The final analyses on the prognostic non-inferiority (primary endpoint) will be available after 2020. Through such series of prospective studies, the proper extent of pulmonary resection for NSCLC is to be defined from prognostic and functional viewpoints. Therefore, especially for JCOG 0802 study, both of two endpoints must meet the hypothetical criteria for lesser resection to be judged as appropriate. We should realize that a true progress in the surgical oncology might be achieved only by a prospective, collaborative comparison as an applied science.

Abstract:
Until the beginning of the new century limited resection for pathologically proven, early-stage lung cancer was not frequently applied in Europe. The main reason for this practice were the results of the randomized phase III trial of the Lung Cancer Study Group published in 1995, showing that for peripheral, clinical T1N0 tumors, lobectomy yields better locoregional control with less recurrences compared to sublobar resection (1). This study was very influential in Europe. A majority of thoracic surgeons adopted the principle that lobectomy was the minimally acceptable lung volume to be resected for patients with an early-stage bronchogenic carcinoma and a low cardiopulmonary risk. Limited resection for lung cancer was only considered for elderly persons, patients with severe chronic obstructive pulmonary disease precluding lobectomy, patients with a high comorbidity score and limited life expectancy due to debilitating disease. Quite a substantial variation in practice is observed, not only within countries but also when comparing North America and Europe. In an interesting analysis of the thoracic surgical databases of the Society of Thoracic Surgeons (STS) and European Society of Thoracic Surgeons (ESTS), some important differences were discovered regarding the daily practice of lung resections performed during the period 2010-2013 (2). Patients in the STS database were more frequently operated by video-assisted thoracic surgery (VATS) compared to the ESTS dataset (63% versus 22%), and were more likely to undergo sublobar resection (43% versus 31%). However, most of the sublobar resections were wedge resections. Anatomical segmentectomies were more frequently performed in the ESTS database than in the STS dataset (7.4% versus 3.9%). For the ESTS patients 30-day mortality of wedge resections was lower compared to the STS data (0.1% versus 1.9%); however, mortality for lobectomy was higher (2.6% versus 1.4%) (2). With the start of European screening studies, although not at the scale of the National Lung Screening Trial, a new clinical problem arose for thoracic surgeons, namely how to deal with small pulmonary nodules and how to limit the false-positive rate? Thoracic surgical issues of screening were addressed in a recent paper by a task force of the ESTS (3). Recommendations were made for implementation of CT screening in Europe focussing on the training of thoracic surgeons, their clinical profile and the use of minimally invasive thoracic surgery. In general, it has been clearly demonstrated that the main goal of surgery for an invasive lung cancer is to obtain a complete resection which is a major prognostic factor. This mostly implies a lobectomy for tumors > 2cm, and at least a lobe-specific systematic nodal dissection as defined in 2005 by a working group of the International Association for the Study of Lung Cancer (IASLC) (4). Unfortunately, quite a lot of resections have to be considered uncertain due to the fact that the required number of lymph nodes, especially mediastinal, have not been removed for further pathological analysis (5). The new adenocarcinoma classification published in 2011 by a common task force of the IASLC , American Thoracic Society (ATS) and European Respiratory Society (ERS) and accumulating phase II data mainly coming from Japan, had important surgical implications (6). As new entities, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were introduced and the confusing term bronchioloalveolar cell carcinoma (BAC) is not used anymore. This clearly resulted in a paradigm shift and the concept of sublobar resection was reconsidered for smaller, early-stage lung cancers < 2cm. Anatomical segmentectomy is generally preferred to wide wedge resection because of concerns of local recurrence (7). Regarding the overall oncological results several meta-analyses have been performed. Their results are somewhat conflicting but overall, good long-term results are described for tumors until 2 cm treated by segmentectomy when no lymph node invasion is present. However, for small, early-stage lung cancer no high-level evidence is currently available and the reported evidence should be interpreted with caution. As most studies were not randomized, there was probably a clear selection bias regarding comorbidity, histology and tumor size. Recent guidelines and evidence from a randomized trial indicate that small nodules of ≤10 mm or ≤500 mm[3] that are clearly 100% pure ground-glass opacities (GGO) on chest CT may be considered as AIS or MIA, and hence may be suitable for close follow-up or sublobar resection rather than a formal lobectomy (8). Subcentimeter lung cancers, currently T1a disease, represent a specific subgroup as they comprise the smallest lesions. It should also be emphasized that for subsolid lesions the current tumor size is determined by the solid or invasive part only which represents a major change in the 8[th] TNM (tumor, node, metastasis) classification (9). For thoracic surgeons another important topic is the accuracy of intraoperative frozen section analysis to determine the intraoperative extent of resection. Recent studies show that a concordance rate of more than 80% can be reached between the frozen section and definitive pathological report (10) . However, AIS and MIA are more difficult to diagnose on frozen section and accuracy becomes less for lesions below 10 mm, which represent the main category to be considered for sublobar resection. This implies that a second intervention to perform a completion lobectomy may be indicated in patients with poor prognostic histological features who initially underwent a limited resection for a presumably low-malignant lesion. In conclusion, sublobar resection is currently more often applied in European countries but more high-level evidence on long-term oncological results is required to refine its indications and make this procedure a generally accepted intervention, not only by thoracic surgeons but also by thoracic oncologists and pulmonary physicians. References 1. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995; 60:615-22; discussion 22-3. 2. Seder CW, Salati M, Kozower BD, Wright CD, Falcoz PE, Brunelli A, et al. Variation in Pulmonary Resection Practices Between The Society of Thoracic Surgeons and the European Society of Thoracic Surgeons General Thoracic Surgery Databases. Ann Thorac Surg. 2016; 101:2077-84. 3. Pedersen JH, Rzyman W, Veronesi G, D'Amico TA, Van Schil P, Molins L, et al. Recommendations from the European Society of Thoracic Surgeons (ESTS) regarding computed tomography screening for lung cancer in Europe. Eur J Cardiothorac Surg. 2017; 51:411-20. 4. Rami-Porta R, Wittekind C, Goldstraw P, International Association for the Study of Lung Cancer Staging C. Complete resection in lung cancer surgery: proposed definition. Lung Cancer. 2005; 49:25-33. 5. Verhagen AF, Schoenmakers MC, Barendregt W, Smit H, van Boven WJ, Looijen M, et al. Completeness of lung cancer surgery: is mediastinal dissection common practice? Eur J Cardiothorac Surg. 2012; 41:834-8. 6. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011; 6:244-85. 7. Sihoe AD, Van Schil P. Non-small cell lung cancer: when to offer sublobar resection. Lung Cancer. 2014; 86:115-20. 8. van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, Vernhout R, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009; 361:2221-9. 9. Travis WD, Asamura H, Bankier AA, Beasley MB, Detterbeck F, Flieder DB, et al. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2016; 11:1204-23. 10. Yeh YC, Nitadori J, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, et al. Using frozen section to identify histological patterns in stage I lung adenocarcinoma of

Abstract:
Since its first report by Churchill and Belsey in 1939, and its evolution in lung cancer management described by Jensik in 1973 (Figure), pulmonary segmentectomy use for early lung cancer diagnosis and treatment has remained controversial. Definitive answers must wait regarding the results of the JCOG and Alliance randomized trials before true standards for surgical care for the lung cancer less than 2 cm are determined. Nevertheless, sublobar resections including wedge resection and segmentectomy are being adopted at an increasing rate compared to its use in previously published large databases (SEER, 5%; ACS NSQIP, 4%). Proper preoperative teaching and intraoperative performance of the technical aspects of sublobar resection are now becoming priorities for general thoracic resident and fellow training in an era where minimally invasive techniques are becoming increasingly the standard of care. General thoracic surgeons must have meticulous attention to detail in performing these resections in order to decrease the likelihood of collateral damage to neighboring segments as well as to minimize local recurrence whether there are performing the operation open, hybrid, standard VATS, uniportal VATS, or robotic. The technical aspects of sublobar resection begin before the patient goes to the operating room, and prime objectives in planning these resections include (1) expertise in the segmental anatomy for that particular patient (2) location and size of the nodule with relation to adjoining segmental bronchovascular components (3) careful study and possible supplementation of high resolution computerized tomography with newer 3-D methods to define the spatial relationships of the nodule and segments (4) pre- and intraoperative methods for locating the nodule if there is suspicion that parenchymal palpation will fail (5) whether to perform wedge resection first or proceed directly to anatomic segmentectomy (6) defining and managing the fissure between segments and recognizing when extended segmentectomy is possible or whether to convert to lobectomy and (7) to use other intraoperative strategies to avoid technique related complications. Preoperative planning includes careful examination of the CT scan in the axial, coronal and sagittal plans in order to get a first appreciation of the depth, size, segmental anatomy and relationship of the nodule bronchovascular elements. Three-dimensional reconstruction can be as simple as navigational bronchoscopy planning images, or newer techniques for total 3-D pulmonary reconstruction which are in development (1). When there is a question of whether up front segmentectomy is to be performed and a part solid or non-solid nodule may not be palpable, intraoperative localization techniques such as navigation bronchoscopy(2) or placement of fiducials/microcoils (3) can be very useful. When there is no preoperative histologic diagnosis, whether a wedge or segmentectomy is performed initially will depend on the location and depth of the lesion as well as the fitness of the patient. Segmentectomy for initial diagnosis with intraoperative frozen section of both the primary lesion and suspicious level 13 and 14 stations can be prudent, especially if wedge resection could compromise performing the segmentectomy(4). In order to avoid positive margins, meticulous attention to detail with compulsive dissection and skeletonizing of the bronchovascular elements must be performed. If it is difficult to preserve the margin in a single segment resection, an extended resection of the parenchyma of adjacent segments or bisegmentectomy can be performed(5). There is controversy regarding the chance for loco-regional recurrence for segmentectomy especially in cases of pure solid lesions or segmentectomies which involve portions of the basilar segments or right upper lobe (6-8). Defining the fissure and the method with which it is divided can be one of the most important yet challenging portions of the operation. A variety of methods to define the fissure have evolved including inflation of the residual lung after segment occlusion, selective inflation of the segment to be removed, or the use of indocyanine green to define the intersegmental vein (4, 5), and the fissure can be divided either with stapling alone or in combination with harmonic scalpel(9). A variety of fibrin sealants are available to decrease postoperative fistulae. With regard to the optimal approach, to date there have been no studies which show any superiority regarding conventional VATs or uniportal VATs for segmental resection, or any difference between the VATs approaches and robotic segmentectomy (10). A recent meta-analysis of over 7438 patients revealed a trend towards increased conversion to open with VATs, while postoperative complications, operation time, length of stay, chest tube duration, and number of lymph nodes were comparable(11). Figure 1 Reference List (1) Yao F, Wang J, Yao J, Hang F, Lei X, Cao Y. Three-dimensional image reconstruction with free open-source OsiriX software in video-assisted thoracoscopic lobectomy and segmentectomy. Int J Surg 2017;39:16-22. (2) Zhao ZR, Lau RW, Yu PS, Wong RH, Ng CS. Image-guided localization of small lung nodules in video-assisted thoracic surgery. J Thorac Dis 2016;8:S731-S737. (3) Donahoe LL, Nguyen ET, Chung TB, Kha LC, Cypel M, Darling GE, et al. CT-guided microcoil VATS resection of lung nodules: a single-centre experience and review of the literature. J Thorac Dis 2016;8:1986-94. (4) Landreneau RJ, D'Amico TA, Schuchert MJ, Swanson SJ. Segmentectomy and Lung Cancer: Why, When, How, and How Good? Semin Thorac Cardiovasc Surg 2017;29:119-28. (5) Oizumi H, Kato H, Endoh M, Inoue T, Watarai H, Sadahiro M. Techniques to define segmental anatomy during segmentectomy. Ann Cardiothorac Surg 2014;3:170-5. (6) Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Locoregional recurrence after segmentectomy for clinical-T1aN0M0 radiologically solid non-small-cell lung carcinoma. Eur J Cardiothorac Surg 2017;51:518-25. (7) Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. The oncological outcomes of segmentectomy in clinical-T1b lung adenocarcinoma with a solid-dominant appearance on thin-section computed tomography. Surg Today 2016;46:914-21. (8) Ueda K, Tanaka T, Hayashi M, Tanaka N, Li TS, Hamano K. What proportion of lung cancers can be operated by segmentectomy? A computed-tomography-based simulation. Eur J Cardiothorac Surg 2012;41:341-5. (9) Kuroda H, Dejima H, Mizumo T, Sakakura N, Sakao Y. A new LigaSure technique for the formation of segmental plane by intravenous indocyanine green fluorescence during thoracoscopic anatomical segmentectomy. J Thorac Dis 2016;8:1210-6. (10) Veronesi G, Cerfolio R, Cingolani R, Rueckert JC, Soler L, Toker A, et al. Report on First International Workshop on Robotic Surgery in Thoracic Oncology. Front Oncol 2016;6:214. (11) Liang H, Liang W, Zhao L, Chen D, Zhang J, Zhang Y, et al. Robotic Versus Video-assisted Lobectomy/Segmentectomy for Lung Cancer: A Meta-analysis. Ann Surg 2017.

Abstract:
In the early 2000s, the revolution in computer-driven radiotherapy technology enabled exquisitely precise direction of radiation beams to specific tumor targets. The advent of 4-dimensional computed tomography (CT), MRI and on-board image-guided intensity-modulated radiotherapy (IMRT), stereotactic ablative radiotherapy (SABR), particle therapy have equipped radiation oncologists with novel tools to tightly conform ablative radiation doses to targets while avoiding inadvertent irradiation of surrounding critical normal structures. SABR, also called stereotactic body radiation therapy (SBRT), as a non-invasive curative therapy, achieves >90% local control, improves survival with minimal toxicity and has become standard therapy in medical inoperable peripheral located stage I NSCLC (1, 2). Particularly for elderly patient, SABR’s effectiveness based on lung cancer-specific survival and progression-free survival is the same in the elderly (>75 year old) as it is the average age population (<75 year old). It also poses no increased toxicity. Compared to historical outcomes with surgery in the elderly, SABR outcome is considered comparable for stage I disease but has less morbidity (3). The pattern of failure study showed that the dominant failure of SABR in stage I NSCLC is distant metastasis (10 to 20%), followed by regional lymph node recurrence (10 to 15%) and then local failure ( 5 to 10%) (4). Up to 1 in 6 patients who received SABR for early-stage NSCLC may develop isolated local-regional recurrence that could be salvaged with definitive treatment. The first long-term results for the largest group of salvaged patients with local-regional recurrence after SABR (n=103) was reported in ASCO 2017 annual meeting (Brooks et al, ASCO 2017 oral presentation in Chicago). 912 patients with clinically early-stage I-II NSCLC from MDACC were treated with SABR with isolated local recurrence (LR, n = 49) or regional recurrence (RR, n = 53). Salvage was performed in 79.6% of LR and 90.6% of RR patients. Median follow-up from time of initial SABR was 57.2 months. 5-year OS was 52% for LR and 27.8% for RR patients. Of LR and RR patients, those receiving salvage had significantly better 5-year OS compared to those not receiving salvage (57.9% LR, 31.1% RR, 0% no salvage; p = 0.006). 5-year OS for LR salvaged patients was not statistically different from patients with NR (53.5% NR, p = 0.92) and 5-year OS for salvaged RR was lower than that of NR (p=0.022). 60% patients never recurred after salvage but subsequent DM occurred in 27.6% of local-regional recurrent patients at a median of 10.5 months. No salvaged patient experienced grade 5 toxicity. There is debate about what is the optimal treatment for operable stage I NSCLC. Majority of the population-based retrospective propensity-matched studies have indicated that SABR has effectiveness comparable to that of surgery for this population, with reported 3-year overall survival rates of 48-91% and local control rates of 85-96% that is significantly better than conventional radiotherapy (5). A pooled analysis of two prospective randomized trials for operable patients showed a better overall survival rate at 3 years for SABR than for surgery (6); however, the efficacy, pattern of failure, and toxicity reported were mostly based upon relatively short follow-up and patient’s number is small; therefore, larger studies with longer follow up are needed and are ongoing around the world. Recently, a phase II prospective study investigating SABR for early-stage NSCLC with median follow-up of 7 years demonstrated outstanding OS of 47% with low rates of local (8%), regional (14%) and distant failure (14%) 7 years after SABR, comparable to those of surgery but with lower toxicity (7). Second malignancy remains one of the most common issues with longer follow-up (21%), again consistent with surgical data. There are two major limitations of SABR in treating early stage NSCLC. First, critical nearby normal tissue dose constraints such as esophagus, bronchial tree, brachial plexus, heart, major vessels etc. may limit the ablative dose that could be safely delivered (8); second, the efficacy of SABR is reduced and toxicity is increased with increasing size of the lesion, particularly when the lesion is >5 cm (9). Most of outstanding clinical outcome with SABR reported in the literature are based on lesions less than 5 cm, typically <3 cm, and not close/next to critical normal structures. Finally, we need to keep in mind that cancer is a biological disease, not just a technologic challenge. As our ability to control local tumors improves with the use of new technology, the importance of systemic disease control grows in parallel—after all, in most cases it is metastatic disease that kills the patient. During the past decade, the development of genomic profile–based targeted therapy and immune checkpoint pathway– based immunotherapy has revolutionized the management of stage IV lung cancer. More and more data indicated that cancer cells killed by radiation release tumor-associated antigens and immunoregulatory cytokines, thereby functioning as a kind of cancer-specific vaccine in situ; they further activate tumor-specific systemic immune responses to eradicate tumors even outside the radiation field (the abscopal effect). These effects seem to be more prominent when the radiation used with immunotherapy involves giving high (ablative) doses, a type of therapy for which we coined the term “I-SABR” (immunotherapy and stereotactic ablative radiotherapy, 10). I-SABR protocols are underway for both early-stage disease and advanced cancer. In summary: SABR/SBRT, a novel non-invasive approach with low toxicity, achieves outstanding clinical outcome and is the standard treatment in medical inoperable stage I NSCLC. It remains controversial whether SABR should be used for operable early stage NSCLC and more randomized studies are ongoing. The dominant pattern of failure after SABR is distant metastasis, followed by regional or intra-lobar failure. Patient with isolated local/regional recurrence should be salvaged aggressively and long-term surveillance is crucial to detect early recurrence and the secondary lung cancer. Combined SABR with systemic therapy such as immunotherapy may further improve the efficacy and cure rate. REFERENCES 1. Timmerman R, et al. Jama. 2010;303(11):1070-6. 2. Onishi H, et al. Cancer. 2004;101(7):1623-31. 3. Brooks ED,et al. Int J Radiat Oncol Biol Phys. 2017;98(4):900-907 4. Senthi S, et al. Lancet Oncol. 2012;13(8):802-9. 5. Shirvani SM, et al JAMA Surg. 2014;149(12):1244-53. 6. Chang JY, et al.Lancet Oncol. 2015;16(6):630-7. 7. Sun B, et al. Cancer. 2017. E-pub ahead of print 8. Timmerman R, et al. JCO. 2006;24(30):4833-9. 9. Tekatli H,et al. J Thorac Oncol. 2017;12(6):974-982. 10. Bernstein MB, el al. Nat Rev Clin Oncol. 2016;13(8):516-24

Abstract:
Background: Despite recent advances, lung cancer remains a disease characterised by negativity, late diagnosis and poor outcomes. The need for advocacy in lung cancer is obvious. Recent years have seen an increase in the number of organisations and individuals advocating for improvements in this disease. With limited resources across all advocacy organisations, using external data and tools from other sources is welcome. Such a source is work undertaken by the Global Lung Cancer Coalition. The Global Lung Cancer Coalition: In 2001, a global search revealed the existence of only nine not-for-profit organisations with an interest in lung cancer advocacy. Of these, only two were lung cancer–specific, the others representing generic cancer or respiratory diseases. In coming together, these organizations established the Global Lung Cancer Coalition (GLCC), an allied group of registered not-for-profit, non-government organizations, dedicated to improving lung cancer outcomes. By 2017, the GLCC has grown to 36 member organisations, from 26 countries and provides a centralised communication and referral network. In recent years, the GLCC has undertaken a number of projects, creating data and tools, for all advocates to use, in their efforts to improve lung cancer outcomes. More information on all of these are available on the GLCC website – www.lungcancercoalition.org. Key Global Lung Cancer Coalition Projects - The Global Lung Cancer e-Atlas The e-Atlas is available on the GLCC website. It is an easily accessible source of international lung cancer data, including all WHO countries. The purpose was to collate lung cancer data from across the globe and uncover international variations. This includes incidence, mortality and survival data. Also, an indication of whether the country has Cancer Registry, has signed up to the WHO Framework on Tobacco and/or has a National Cancer Plan. The e-atlas brings all of this information together in an easily accessible place. This is a data resource for lung cancer professionals and campaigners. It is easy to compare data across countries and easy to create graphs, for download into powerpoint presentations and reports. This resource has already been used by many advocates, in discussions with politicians and health policy makers, to highlight differences in inter-country survival. The e-atlas will be updated, as international data sets are updated. Where possible, we will also add links to national lung cancer data sources. International Consumer Polls GLCC commissioned IPSOS/MORI to undertake two consumer polls in GLCC member countries in 2011 and 2013. These examined issues of stigma and also of general public awareness of lung cancer symptoms. In 2017, these two polls are being repeated by Populus and will be undertaken in 25 countries. This will provide update information in GLCC countries covered by the original polls and new information for newer GLCC member countries. Smoking stigma associated with lung cancer and poor public awareness of signs and symptoms of the disease are of obvious importance. Such polls provide valuable information for advocating and campaigning for improvement and change. Global Lung Cancer Research data The GLCC commissioned researchers at King’s College in London, to undertake some bibliometric research, to map published lung cancer research, across the globe. This type of research involves the quantitative analysis of publications and research activity, using complex bespoke algorithms This work was published, as an open access article, in June 2016 in the Journal of Thoracic Oncology. (Agarwal A, et al, ‘The State of Lung Cancer Research – A Global Analysis)’. Results of this work show the relative lack of lung cancer research globally. Individual Country Toolkits have been created to raise awareness of lung cancer research nationally and advocate for more. GLCC has commissioned further research in this area, investigating how published research is used – for example, does it change practice, how is the research implemented and what research is media reported. Information on Lung Cancer – Topical Factsheets GLCC has created factsheets in topical area, available for download from the GLCC website. These include Information on Clinical Trials and the relatively new therapy field of Immunotherapy. The Immunotherapy Factsheet is available in 16 languages. Factsheets are now also available on Lung Cancer Screening and Lung Cancer and Stopping Smoking. These are available for everyone to download and distribute. Lung Cancer Awareness Information Sheets The GLCC has created Awareness leaflets. These are designed for the general public, to inform on lung cancer – What to look out for? What to do? Where to go for help and support? The leaflets have been translated into 13 languages and are available for download on the Resource section of the website. In this presentation, all of the above will be expanded on. We invite all who advocate for improvements in lung cancer to use these resources.

Abstract:
The United States has no formal system of health technology assessment, compared to, for example, the system in the United Kingdom and many countries worldwide. In the U.S., certain federal agencies review and recommend approval of drugs and devices, while others make determinations regarding reimbursement of costs of treatment and other interventions. With the cost of health care in the U.S. skyrocketing in the absence of cost controls, many organizations, e.g., the American Society of Clinical Oncology, the National Comprehensive Cancer Network, Memorial Sloan Kettering Cancer Center and others, have developed “value frameworks”. In virtually all cases, however, the frameworks were developed without input from patients, their caregivers or patient advocates. They were developed from evidence obtained in randomized controlled trials and did not include real-world evidence, such as from observational studies or patient experience reports. Decisions about what patients value were often made by clinicians and economists and not by the patients whose lives would be impacted by the recommendations.The situation becomes even more complex when one considers that all patients do not share the same values with regard to outcomes. While a younger, otherwise healthy patient might accept significant treatment toxicity in order to extend life, an older, less healthy patient might choose treatment that is likely to be less toxic. As treatment costs escalate, financial toxicity is also a consideration and varies among individual patients. A treatment that imposes significantfinancial burden on one individual might not be perceived as overly costly by another.Family/caregiver preference also needs to be taken into consideration, as all demographic groups do not share the same preferences or values. Whereas in some groups, the patient’s preference is what counts, in others, family members are much more involved in decision making.In May 2015, researchers from the American Institutes for Research and the Mayo Clinic published a study based on extensive interviews with 721 patients.

Abstract:
Regarding the main disadvantages to access: 1. Where there are structural factors that grant the right and Promote coverage, bureaucratic issues arise that Complicate access. 2. There is in general an underutilization of the available public resource, for lack of information. 3. Many patients who depend on public coverage lack of an education from which they can empower themselves situation. Many times they lack the knowledge and Tools to expand their options. 4. The delay or inefficient response by the public coverage remains, even increases, or extent a claim made by patients and their relatives. 5. Delays both in the delivery of medicines and in obtaining shifts, in order to conduct a study. Problems of transfers, Great distances to treatment centers. Mexico, Brazil, Peru, Argentina and Chile to mention some examples in Latin America we have very fragmented health systems, little or no budget for avant-garde treatments like Immunotherapy or targeted therapies. Lung Cancer patients often do not know their rights, they do not empower themselves and require the inclusion of these therapies. While efforts have been made to tighten anti-smoking laws, there is a long way to go and educate to create awareness.

Abstract:
Background of Japanese lung cancer advocacy In Asian countries, the concept of cancer advocacy has not been sufficiently recognized. In Japan, there had been few groups of lung cancer patients for a long time, and West Japan Oncology Group (WJOG) has practiced cancer advocacy learned from the USA and Europe as a citizen lecture and a guidebook for patients. We noticed that interactive efforts involving patient groups, companies, academia and governments are necessary rather than providing one way information. In recent years, Lung Cancer Society (JLCS) has led the lung cancer advocacy, and adopted the 2014 Kyoto Declaration, which Representatives of the society, lung cancer patients, citizens, medical personnel, government, companies and research institutes, declared the will to the improvement of lung cancer medical care in cooperation. First, the medical improvement committee against lung cancer was organized to to realize the goal of the Kyoto Declaration, and The committee has carried out the following activities. Initially, the ambassador was commissioned to a lung cancer survivor, a futsal professional athlete and one medical school student of a leader of the idol singer group. In line, we currently commission six medical school students, students of pharmacy, and nursing students. One of our main activities is to provide information on lung cancer medical care using websites and events. In addition to the public lecture, medical workers seminar, the event by the patient association had been supported. These activities are open to the public so that citizens and medical staff can recognize widely in cooperation with medical media. Also, in collaboration with the Lung Cancer Society, we are also requesting early approval of new therapeutic agents. Evaluation of Japan's advocacy To evaluate the awareness and attitude of lung cancer advocacy activity among patients, medical workers, and the general population in Japan, web survey was planned for the perceptions of Kyoto declaration and JLCA (Japanese alliance for lung cancer advocacy) events which were carried out by JLCS in these 2 years. Furthermore, we tried to reflect the questionnaire result in the subsequent activity plan. An internet survey was conducted which contained 6 closed-ended (selection one or free answers) and open-ended questions, depending on the JLCA network population in June 2016. Results By October 2016, 109 people of responded involving 36% of patients and their family, 25% of MD and medical worker, 19% of pharmaceutical company officials and 16% of news media. Perception of Kyoto declaration was 21% of attendee, 27% of well-known, 13% of partial known and 39% of non-awareness. Also the number of participants to the events of JLCA is, 49% of 0 times, 17% 0f 1-2 times, 24% of 3-4 times and 11% of more than 5 times. The most sympathy events ware voted to 1) lecture by a physician 57%, 2) lecture by survivor and the participants WCLC of cancer patients 46%, 3) information in the facebook and the web site 46% 4) citizen open lecture of lung cancer 39%, 5) Performance by society ambassador 38%, 6) advocacy program in annual meetings 26% and 7) Medical seminars around the country 26%. The proportion of respondents who have a certain reputation in the activities of JLCA was 76%.The requests to JLCA is, 1) is the most participation opportunities for information of new treatment and participation opportunities to clinical trial, followed by 2) wish to participate to all the programs in the Society. Looking for the next difference 1. Activities in the next fiscal year, reflecting the results of the questionnaire, citizen public lectures consisted mainly of lectures by prominent oncologist, announcements of representative survivors, moderators and lectures by public ambassadors. Events were held in major cities and various places across Japan. Also The lung cancer society organizes the patient advocacy program throughout the annual meeting every year. We provide travel grants from 2016 to facilitate patient and family attendance. 2.The committee holds medical seminars in Tokyo four times a year. The theme was the latest current information surrounding lung cancer from time to time, introduction of new treatment and activity of patients group. In addition, journalists, television reporters and medical writers were invited to provide information to the public widely by articles posting. 3. Through the website, we provide topics on diagnosis and treatment for lung cancer using video, activity policy and advocacy activities of the lung cancer society, documentary on participation of the international conference of the patient association. In conclusion, participants from different professions gathered for the purpose of improving lung cancer medical care, shared recognition was born among the participants, and empathy was also obtained with the public relations ambassador. Meanwhile, because of different professions and position, the hope of the content of activities was diverse, and it seems necessary to enhance the priority business that can be shared.

Abstract:
Smoking and lung cancer Since the 1950’s, smoking has been associated with lung cancer (US National Llibrary of Medicine, 2017). Lung cancer is the most common cancer worldwide and the biggest cancer killer (World Health Organisation, 2017). The majority of lung cancer diagnoses are due to smoking (US National Llibrary of Medicine, 2017), yet these frightening statistics have not deterred people around the globe from smoking. The World Health Organisation estimated that, in 2015, 1.1 billion people smoked tobacco. Within this cohort are lung cancer patients and their families, unable or unaware of why they should quit. This presents a great challenge to patient advocates worldwide. Awareness Awareness of the significant health risks associated with smoking vary around the world, so the role of the patient advocate also varies from country to country. In 2013 the Global Lung Cancer Coalition launched a survey, carried out by Ipsos MORI, investigating awareness of the symptoms of lung cancer and smoking prevalence in 21 countries. Researchers found that across all the countries, 22% of people surveyed admitted they could not name any symptoms of the disease. Over 17,000 people were surveyed, among them former smokers were slightly more likely to be aware of symptoms than current smokers or people who have never smoked. Multiple studies have replicated similar differences in awareness of the link between smoking and lung cancer across countries. Research performed by the Irish Cancer Society in 2015 found that; 92 out of 100 smokers know that smoking causes lung cancer. In contrast, the Global Adult Tobacco Survey (2010) found that in China; 23% of adults believe smoking causes stroke, heart attack, and lung cancer. While every country requires a message specific to their population, the common theme is stopping smoking is the most important thing the public can do to reduce their risk of lung cancer and it is never too late to benefit from stopping, even after a diagnosis of a smoking-related disease. Benefits of quitting Smoking not only increases your risk of lung cancer, but of multiple cancers, heart disease, stroke, lung disease, and fertility and pregnancy problems (US National Library of Medicine, 2017). Tobacco smoke contains around 7,000 chemicals. Many of these are poisonous and over 60 are known to be cancer causing. For people already diagnosed with lung cancer, smoking cessation can seem pointless but there are clear benefits to stopping smoking including better treatment efficacy, fewer side-effects, less risk of recurrence and less risk of developing other smoking-related health problems (American Society of Clinical Oncology, 2016). There are immediate and long-term health benefits of quitting for all smokers, including those already diagnosed with lung cancer, including (World Health Organisation, 2017): Within 20 minutes, your heart rate and blood pressure drop After 12 hours, the carbon monoxide level in your blood drops to normal Within 2-12 weeks, your circulation improves and your lung function increases At 1-9 months, coughing and shortness of breath decrease By 1 year, your risk of coronary heart disease is about half that of a smoker's Within 5-15years, your stroke risk is reduced to that of a non-smoker By 10 years, your risk of lung cancer falls to about half that of a smoker and your risk of cancer of the mouth, throat, oesophagus, bladder, cervix, and pancreas decreases Within 15 years, the risk of coronary heart disease is that of a non-smoker’s. Role of advocates Advocates have an opportunity to promote smoking cessation on a National scale as well as at an individual level. This can seem like an overwhelming task in light of the significant health burden smoking presents, however international support is available. In 2005 The World Health Organisation Framework Convention on Tobacco Control (WHO FCTC) was created. This evidence-based treaty reaffirms the right of people to the highest standard of health, provides legal dimensions for international health cooperation and sets high standards for compliance. Each MPOWER measure corresponds to at least 1 provision of the WHO Framework Convention on Tobacco Control. The 6 MPOWER measures are: Monitor tobacco use and prevention policies Protect people from tobacco use Offer help to quit tobacco use Warn about the dangers of tobacco Enforce bans on tobacco advertising, promotion and sponsorship Raise taxes on tobacco. At an individual level, advocates can play a vital role in encouraging lung cancer patients and their families to avail of behavioural support and medication to assist their smoking cessation efforts. Lung cancer patients are burdened with elevated levels of distress in comparison to other cancers (Zabora et al., 2001) and research suggests that stigma and the association with tobacco is a very real issue for lung cancer patients (Chapple et al., 2004). This is in addition to being diagnosed with the biggest cancer killer worldwide, a probable late stage diagnosis, poor prognosis and debilitating symptoms. For the lung cancer patient, advocate guidance and support is vital to successfully quit smoking. People diagnosed with cancer often keep quiet about their smoking because (American Society of Clinical Oncology, 2016): they fear judgement or blame from their family or doctor they think they might get less support for their cancer treatment the think it is pointless to stop as they already have cancer they believe smoking helps them cope with stress they have tried to stop before unsuccessfully. The challenge for patient advocates is balancing this support at an individual level with the need to evoke change at a National and International level.

Background:
Although stereotactic ablative body radiotherapy (SABR) is now well established as a treatment for stage I non-small cell lung cancer (NSCLC), there is limited evidence that it is as or more effective than conventional fully fractionated radiotherapy (CRT). We conducted a randomized trial to determine if SABR results in longer time to local failure than CRT.

Method:
This was a multicentre trial of the Trans-Tasman Radiation Oncology Group (TROG) and Australasian Lung Cancer Trials Group, registration number NCT01014130. Patients were eligible if they had biopsy proven stage I (T1- T2a N0M0) NSCLC based on PET and were medically inoperable or refused surgery. Patients had to be performance status ECOG 0 or 1, and the tumor had to be at least 2 cm or more from the bifurcation of the lobar bronchus. Patients were randomized 2:1 to SABR (54 Gy in 3 fractions, or 48 Gy in 4 fractions, depending on proximity to the chest wall, to the isodose covering the PTV) or to CRT (66 Gy in 33 fractions or 50 Gy in 20 fractions). The primary objective was to compare time to local failure between arms. Assuming that the rate of local failure at 2 years would be 10% in patients randomized to SABR versus 30% in patients randomized to CRT, 100 patients were required. All living patients were followed for a minimum of 2 years. Analysis was based on the intention to treat principle. Funding: In Australia: Grant #1060822 was awarded through Cancer Australia. In New Zealand, The Cancer Society of New Zealand and the Genesis Oncology Trust.

Result:
Between 12/09 and 6/15, 101 patients were enrolled. There were 56 males and 45 females with a median age of 74 years (range 55-89), ECOG performance status – 28 were 0, 71 were 1 and 1 was 2. TNM stage was T1N0M0 in 71 and T2aN0M0 in 30. Sixty six patients were randomized to SABR and 35 patients to CRT. Patients randomized to SABR had superior freedom from local failure (HR = 0.29, 95% CI 0.130, 0.662, P=0.002) and longer overall survival (HR = 0.51, 95% CI 0.51, 0.911, P=0.020). Worst toxicities by arm were: CRT grade 3, 2 patients; SABR grade 4, 1 patient and grade 3, 9 patients.

Conclusion:
In patients with inoperable stage I NSCLC, compared with CRT, SABR resulted in superior freedom from local failure and was associated with an improvement in overall survival.

Background:
Stereotactic radiotherapy (SBRT) is an efficient treatment for early stages of inoperable NSCLC. SBRT may, however, also be used as salvage treatment for recurrent disease. This retrospective study reports and compares the outcome of patients initially treated with surgery and patients initially treated with curative radiotherapy (RT).

Method:
All cases of NSCLC treated with RT with curative intent at our institution are prospectively recorded. We here report the results of 114 cases treated at our institution July 2009 to June 2016 with SBRT as salvage therapy. The doses used for peripheral located tumors have been 45-66 Gy (central doses) in 3 fractions (F) while centrally located tumors have been treated with 50-78.4 Gy/ 5-8 F. The patients have been treated with IMRT or VMAT. A group of 80 patients had surgery initially (Surg-Grp): Resection 19 (24%), lobectomy 56 (70%), bi-lobectomy 1 (1%), and pneumonectomy 4 (5%). Another group of 34 patients was initially treated with RT (RT-Grp): SBRT 30 (88%) and conformal chemo-RT 4 (12%). All patients had more than 1 year of potential follow-up.

Result:

The patient characteristics

Surg-Grp RT-Grp p-value Age (yr.) 72.6 (55.1; 89.3) 71.7 (53.5; 87.1) 0.56 Female /Male 45 / 35 18 /16 0.91 PS 0-1 55 (69%) 15 (44%) PS 2 21 (26%) 15 (44%) PS 3 4 (5%) 4 (12%) Median FEV1 (L/sec) 1.54 (.39-2.72) 1.37 (.42-2.75) 0.59 Time from initial treatment to salvage treatment (mo) 22.4 (0.6; 272) 20.7 (4.4; 100) Salvage RT 45 Gy/3 F 10 (13%) 9 (26%) 66 Gy/3 F 54 (68%) 18 (53%) 50 Gy /5 F 3 (4%) 0 78.4 Gy /8 F 13 (16%) 7 (21%)

The median, 1, 2, 3, and 4 year overall survival was 50.5 mo, 85%, 72%, 59%, and 59 % in the Surg-Grp and 31.3 mo., 71%, 55%, 46%, and 46% in the RT-Grp, (p=.13).

Conclusion:
SBRT gives excellent survival used as salvage therapy after surgery and curative intended radiotherapy.

Background:
Five-year local control rates in early-stage NSCLC following stereotactic ablative radiotherapy (SABR) are approximately 90%. However, the resulting focal fibrosis can be difficult to distinguish from tumor recurrences. We investigated the incidence, and patterns of change in previously reported high-risk radiological features (HRF’s), in patients who were known to have no local recurrence.

Method:
Patients treated using volumetric modulated arc therapy SABR were eligible if follow-up CT-scans were available for at least 2 years. Five clinicians who were unaware of clinical outcomes scored the following HRF’s on CT-scans: enlarging opacity(EO), sequential enlarging opacity(SE), enlarging opacity after 12 months(EO12), bulging margin(BM), loss of linear margins(LOM), cranio-caudal growth(CCG) and loss of air bronchogram(LOB). CT-scans were reviewed at a workstation using in-house plugin customized for ClearCanvas (Synaptive Medical, Toronto, Canada). After each review, clinicians recommended follow-up procedures based on previously published recommendations.

Result:
In 88 patients (747 CT-scans) evaluated, the HRF’s most frequently recorded by ≥3 observers on at least one follow-up CT-scan were EO (64.8%), EO12 (50.0%) and SE (13.6%). Cumulative mean incidence rates of each HRF per category are displayed (figure). Fifty-six patients developed EO in the first year, and 46 of these patients developed subsequent EO12. In 76 patients who developed EO12, 30 had no EO previously. The presence of ≥3 HRF’s have been associated with recurrences, and this was observed in 20 patients. When HRF’s were identified, clinicians indicated that they were either very certain (mean: 37.2%, range: 11.9-70.4%) or moderately certain (mean: 51.2%, range: 26.5-87.1%) about the presence of this feature. In routine care, only 6 patients underwent PET-scans because of a suspected local recurrence, and 4 underwent an attempt at biopsy. Figure 1



Conclusion:
Although HRF’s on CT-scan develop in more than 50% of patients without local recurrence after SABR, only 23% had ≥3 HRF’s.

Abstract not provided

Background:
The CONVERT Trial is a multicentre phase III study which recruited 547 patients with limited-stage SCLC from April 2008 to November 2013. Patients were randomised to receive once daily (66Gy in 33 fractions) or twice daily (45Gy in 30 fractions) radiotherapy concurrently with chemotherapy. The primary endpoint was overall survival. This study investigates the effect of non-compliance to radiotherapy protocol on survival for the CONVERT Trial.

Method:
489/557 received chemo-radiotherapy according to protocol. As part of the CONVERT trial quality assurance (QA) programme, 94 patient datasets (19.2%) treated with concurrent chemoradiotherapy (n=489) were reviewed and deviations from protocol were categorised as acceptable, acceptable variation and unacceptable variation using the Global Harmonisation Group (GHG) variation definitions. Organ at risk outlining (heart, spinal canal and lung minus planning target volume (PTV)), target delineation and margins applied, PTV coverage, treatment planning technique and radiotherapy treatment time were reviewed and classified according to the GHG definitions. A multiplicative factor (F) was calculated for each treatment plan, based on the GHG definitions. A low factor indicates a low number of protocol deviations. Protocol deviations were correlated with survival and number of patients recruited per centre.

Result:
94/489 patients were included in this analysis (19.2% of the randomised patients). The median number of patients recruited per centre was 6 (range 1-109). Protocol deviations were categorised as acceptable (57.6%), acceptable variation (23.3%) or unacceptable variation (19.1%). Amongst the unacceptable variations the PTV coverage was the most common deviation to protocol. In these 71 patients (75.5%) the dose distribution within the PTV was greater than 7% of the prescribed dose. Patients with increasing number of organ at risk outlining protocol deviations and with an increase in the multiplicative factor (F) had a lower survival. Further details will be presented at the meeting including survival in the 3 GHG categories. Centres recruiting >25 patients were found to have a lower number of protocol deviations (median 2, range 2-3) compared with centres recruiting fewer than 25 patients (median 3, range 0-4.5), and were most likely to delineate organs at risk correctly.

Conclusion:
High recruiting centres are most likely to comply with a trial protocol. Overall survival was affected by the number and type of protocol deviations, highlighting the importance of a robust trial QA programme in prospective radiotherapy trials.

Background:
Radiation (RT) dose to the heart was a predictor of inferior overall survival (OS) in the non-small cell lung cancer trial RTOG 0617, but little data quantifies cardiac morbidity for small cell lung cancer (SCLC) patients treated with RT.

Method:
The Surveillance, Epidemiology, and End Results (SEER) Program database and Medicare claims data were queried to establish rates of cardiac events (CE) among SCLC patients treated with chemotherapy (CTX) +/- RT. CE were defined as any new cardiac diagnosis including ischemic disease, cardiomyopathy, dysrhythmia, heart failure, and pericarditis. Chronic/pre-existing diagnoses were not counted as events. CTX-only patients were matched to CTX + RT patients to account for start date of RT. Second phase of propensity score matching (PSM) balanced demographical and clinical differences. Multivariate analysis (MVA) determined effect of tumor and RT covariates on CE and OS. Kaplan-Meier and cumulative incidence (CI) function curves were generated.

Result:
From 2000 – 2011, 7,060 patients were available: 2,892 (40.9%) limited-stage and 4,168 (59.0%) extensive-stage. As expected, CTX + RT patients had better OS (p < 0.001). OS for the CTX + RT and CTX-only groups: 35.0 vs. 21.4% at 12 months, and 6.6 vs 2.3% at 60 months, respectively. RT was associated with CE (p = 0.008), with CI as follows for the CTX + RT and CTX-only groups: 36.4 vs. 35.4% at 12 months, and 44.1 vs 39.0% at 60 months, respectively. MVA demonstrated higher hazard ratio of CE for extensive-stage patients (p < 0.001), black race (p < 0.001), and increased Charlson-Deyo score (p = 0.001). After PSM, 5,286 patients were included. Again, CTX + RT patients had better OS (p < 0.0001). OS for the CTX + RT and CTX-only groups: 30.6 vs. 22.5% at 12 months, and 5.3 vs 2.7% at 60 months, respectively. RT was still associated with CE (p = 0.033) after PSM, with CI of CE for the CTX + RT and CTX-only groups: 36.3 vs. 34.8% at 12 months, and 43.0 vs 38.6% at 60 months, respectively. Tumor laterality (p = 0.84) and RT modality (p = 0.62) were not associated with CE, though low numbers were treated with intensity-modulated versus 3D conformal RT (1:15 ratio).

Conclusion:
In this large database study we demonstrated RT is associated with an absolute increase in the rate of CE at 5-years of approximately 5%. Further evaluation of cardiac sparing radiation techniques should be evaluated for patients with SCLC.

Background:
During standard concurrent chemoradiotherapy (CRT), patients with NSCLC often report severe symptoms that should be routinely assessed and managed. According to the United States FDA specified standards, patient-reported outcome (PRO) instruments used in clinical trials should have good measurement properties of reliability, validity, and the ability to detect change. This quantitative study used a validated PRO symptom-assessment tool, the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), to compare a cluster of CRT-related symptoms in NSCLC patients receiving CRT, and to investigate the sensitivity of a composite score of these symptoms.

Method:
We enrolled patients with locally advanced NSCLC (n=118) who underwent intensity-modulated radiation therapy (IMRT, n=33), 3-dimensional conformal radiation therapy (3DCRT, n=22), or proton-beam therapy (PBT, n=63). Patients completed the MDASI-LC weekly for up to 12 weeks. Two criteria used for item selection to form a subscale for CRT-related symptoms: MDASI-LC items rated 4-10 in >25% of observations, and that increased significantly during therapy (by mixed-effect models). A CRT-symptom score (MDASI-LC-CRT) was generated by averaging scores from those symptoms. The MDASI-LC-CRT’s responsiveness to treatment was examined by within-person change over time and effect size (ES) statistics.

Result:
Six symptoms—pain, fatigue, drowsiness, lack of appetite, sore throat, coughing—were identified as the most-severe CRT-related symptoms during and after therapy. Before CRT, MDASI-LC-CRT scores did not differ by treatment (3DCRT 2.2±1.8, IMRT 1.6±1.5, PBT 1.8±1.7, p=0.329). At the end of CRT, MDASI-LC-CRT was highest for 3DCRT (4.85±2.40), followed by IMRT (3.18±1.85) and PBT (2.29±1.65). A large ES (1.24) was found for 3DCRT vs. PBT; medium ES were found for 3DCRT vs. IMRT (0.78) and IMRT vs. PBT (0.51). The ES for pre-CRT vs. post-CRT difference (1.8±1.7 vs. 3.0±2.1) was medium (0.63) for all patients, large for 3DCRT (1.25) and IMRT (0.93), and small for PBT (0.28). The MDASI-LC-CRT score increased significantly over treatment (estimated weekly increase=0.21, p<0.0001), peaking at week 7 (95%CL=6.2-7.8, p<.0001) and then decreasing to week 12 (est=0.18, p=0.001). Significantly larger weekly increase was reported by 3DCRT and IMRT patients, compared with PBT patients (all p<0.0001).

Conclusion:
The MDASI-LC-CRT is a sensitive indicator of dynamic change in major symptom burden during CRT. This subscale could be routinely used for symptom monitoring while patients are going through CRT and appropriate supportive measures could be instituted early. PBT was the best tolerated of the radiation modalities when given concurrently with chemotherapy with the least worsening of symptoms over the CRT period.

Abstract not provided

Background:
Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. We report the results of a randomized phase II trial of anetumab ravtansine compared to vinorelbine in patients with advanced malignant pleural mesothelioma (MPM) who have high mesothelin expression and have progressed on platinum/pemetrexed-based first-line chemotherapy (NCT02610140).

Method:
Patients (≥18 years) with locally advanced or metastatic MPM with progressive disease following first-line treatment with pemetrexed-based chemotherapy, with or without bevacizumab, were eligible. Patients were pre-screened based on obligatory tumor staining for mesothelin as determined by the Ventana MSLN (SP74) immunohistochemistry assay. The primary efficacy endpoint was progression-free survival (PFS) per central radiologic review using modified RECIST criteria for MPM. Secondary objectives included overall survival, tumor response, and safety. Patients were randomized in a 2:1 ratio to anetumab ravtansine 6.5 mg/kg Q3W IV or vinorelbine 30 mg/m[2] QW IV.

Result:
A total of 166 patients were randomized to anetumab ravtansine and 82 to vinorelbine; 3 and 10 patients, respectively, not receiving treatment were included for efficacy but not safety assessments. The treatment arms were evenly balanced, with 73% male, 64% ECOG performance status 1, 96% epithelioid histology, and a mean 2.5 (±2.4) months since last progression. The median duration of treatment (anetumab vs vinorelbine) was 12.6 weeks (range 3-61) vs 13.0 weeks (range 1-43). Treatment-emergent grade (G) ≥3 adverse events (AEs) were seen in 85 (52.1%) and 53 (73.6%) of patients, respectively. G3/G4 neutropenia (22.2%/16.7%) occurred in the vinorelbine arm whereas corneal epitheliopathy (39.3% all grade, 1.8% G3) was distinct for the anetumab ravtansine arm. Serious AEs (any grade) were similar; 52 (31.9%) vs 25 (34.7%). Treatment-emergent AEs leading to dose modification were 42.9% in the anetumab ravtansine arm and 80.6% in the vinorelbine arm. There was one treatment-related G5 event in each arm. Median PFS was 4.3 months (95% CI:4.1, 5.2) for anetumab ravtansine vs 4.5 months (4.1, 5.8) for vinorelbine; hazard ratio 1.22 (0.85, 1.74), p=0.859. Fourteen (8.4%) patients in the anetumab ravtansine arm had an objective response vs 5 (6.1%) in the vinorelbine arm, with no complete responses. Interim median overall survival was 10.1 mo (7.6, -) vs 11.6 mo (7.7, 12.5), respectively, p-value 0.721.

Conclusion:
In relapsed MPM, anetumab ravtansine was not superior to vinorelbine with respect to PFS.

Background:
There is an increasing interest in the use of IO therapy in Mesothelioma (MPM). We previously reported on the effect of nivolumab (s.a) in patients with recurrent MPM with a disease control rate of 50% at 12 weeks. We therefore decided to test the effect of the combination of nivolumab and ipilimumab in recurrent MPM.

Method:
Patients with previously treated MPM and a PS of 0-1 are consented in this single arm prospective study. Pleural lesions must be available for biopsy before and after 6 weeks of treatment.Nivolumab is administered at a fixed dose of 240 mg (q2w) until progression and combined with ipilimumab (1mg/kg) on week 1, 7, 13 and 19. CT scans are performed every 6 weeks for analysis and duration of response. The primary endpoint is disease controle rate at 12 weeks. Translational research is performed on paired biopsies. A Simon’s minimax two-stage design is used to identify a DCR of >50%. Therefore 33 patients will be included.

Result:
From October 2016 until August 2017 38 patients gave informed consent. Three patients did not start due to progression or impossibility to biopsy. Two stopped after 1 cycle (due to progression or withdrawn consent). At time of analysis (August 29) 25 patients could be evaluated for response. At 12 weeks a DCR of 72% (18/25) and ORR of 28% (7/25) is observed. Two patients continued treatment after progression at 6 weeks; 1 achieved a PR after 4 months , and the other one is stable. Of the first 11 patients that have been in study for 6 months, 5 have PR, 1 SD and 4 PD. Toxicity is mild. SAE’s reported in the 38 patients occurred in 11 patients with grade 3 or 4 toxicity. No grade 5 toxicity was observed.

Conclusion:
In this interim analysis nivolumab plus ipilimumab meets the primary endpoint for patients with recurrent malignant mesothelioma. Toxicity is mild. The full data set will be presented at the WCLC.

Background:
It has been widespread practice across Europe to irradiate diagnostic or therapeutic chest wall (CW) intervention sites in patients with malignant pleural mesothelioma (MPM) post-procedure - a practice known as prophylactic irradiation of tracts (PIT). This study aims to determine the efficacy of PIT in reducing the incidence of CW metastases following a chest wall procedure in MPM.

Method:
In this multicentre phase III randomised controlled trial, MPM patients following a chest wall procedure were randomised 1: 1 to receive PIT (within 42-days of procedure) or no PIT. Large thoracotomies, needle biopsy sites and indwelling pleural catheters were excluded. PIT was delivered at a dose of 21Gy in 3 fractions over 3 consecutive weekdays using a single electron field adapted to maximise coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CW metastases within 6 months from randomisation, assessed in the intention-to-treat population. Stratification factors included epitheloid histology and intention to give chemotherapy. Trial registration number NCT01604005.

Result:
375 patients (186 PIT and 189 no PIT) were randomised between 06/2012-12/2015 from 54 UK centres. Comparing PIT vs no PIT, %male patients was 89.8/88.4%, median age 72.8/74.6 years, %ECOG PS (0,1,2) 32.2,56.5,11.3/23.8,56.1,20.1%, %confirmed epithelioid histology 79.6/74.1%, and %with intention to give chemotherapy 71.5/71.4%. The chest wall procedures were VATS (58.1/51.3%), open surgical biopsy (2.7/5.3%), local-anaesthetic-thoracoscopy (26.9/27.0%), chest drain (5.9/8.5%) and others (6.5/7.9%) for the PIT vs no PIT arm respectively. Radiotherapy was received as intended by 181/186 patients in the PIT arm. The proportion of CW metastases by 6 months was 6/186 (3.2%) vs 10/189 (5.3%) for the PIT vs no PIT arm respectively (odds ratio 0.60 [95% CI 0.17-1.86]; p=0.44) and by 12 months 15/186 (8.1%) versus 19/189 (10.1%) respectively (OR=0.79 [95% CI 0.36-1.69];p=0.59). Cumulative incidence of CW metastases at 6months/12 months/24 months was 3.3/8.5/10.0% in the PIT arm vs 5.6/10.9/18.7% in the no PIT arm. Evaluable patients who developed CW metastases reported a mean increase in visual analogue scale pain score of 13.3 (p<0.01) compared to baseline. Skin toxicity was the most common radiotherapy-related adverse event in the PIT arm with 96(51.6%) grade 1, 19(10.2%) grade 2, and 1(0.5%) grade 3 radiation dermatitis (CTCAE V4.0). There were no other grade 3 or higher radiotherapy-related adverse events.

Conclusion:
There is no role for the routine use of PIT following diagnostic or therapeutic CW procedures in patients with MPM.

Abstract not provided

Background:
Malignant pleural mesothelioma (MPM) has a high symptom burden and early specialist palliative care (SPC) may have a beneficial role for these patients. We examined the effect of early SPC in patients with MPM.

Method:
Participants with newly diagnosed MPM (within the last 6 weeks) were randomised to early SPC integrated with standard care, or standard care alone, in a 1:1 ratio. SPC visits were 4 weekly throughout the study period. Quality of life (QoL) and mood were assessed at baseline and every 4 weeks for up to 24 weeks with the EORTC QLQ–C30 questionnaire for QoL and General Health Questionnaire (GHQ-12) for anxiety/depression. The primary outcome was the change in EORTC C30 Global Health Status (GHS) QoL 12 weeks after randomisation.

Result:
174 participants underwent randomisation with 148 (85.1%) completing the primary outcome. The two groups were well matched after randomisation. Median (IQR) age was 72.6 (68.5-78.3) years and 139 (79.9%) were male. Epithelioid was the most common MPM subtype in 136 (78.2%) cases, ECOG PS was 0 in 66 (37.9%) and 1 in 108 (62.1%) participants. At randomisation, 134 (77.0%) participants reported dyspnoea and 100 (57.4%) had chest pain. At least 1 cycle of chemotherapy was completed in 103 (59.2%) participants. At 24 weeks 30 (17.2%) participants had died. Table 1 presents the primary and secondary outcome data. 68 (78.2%) participants in the intervention arm completed all scheduled monthly SPC visits at 12 weeks, and 46 (52.9%) at 24 weeks. 15 (17.2%) participants in the control arm were referred to SPC within 12 weeks, and 30 (34.5%) by 24 weeks.

Table 1. Primary and secondary outcomes

	Control	SPC	Mean difference*	p=
Mean (SD) GHS QoL 12 weeks	59.5 (SD 21.2)	60.2 (23.6)	1.8 (95% CI -4.0 to 8.5)	0.60
Mean (SD) GHS QoL 24 weeks	63.7 (SD 19.8)	61.3 (20.8)	-2.0 (-8.8 to 4.6)	0.55
Mean (SD) GHQ-12 anxiety / depression scores 12 weeks	2.6 (3.2)	2.2 (3.0)	-0.6 (-1.5 to 0.4)	0.24
Mean (SD) GHQ-12 anxiety / depression scores 24 weeks	2.1 (2.55)	1.75 (2.5)	-0.4 (-1.2 to 0.4)	0.28
Median (95% CI) survival (months)	12.6 (10.7-19.7)	11.5 (9.8-15.9)	-	0.51
Mean (SD) GHS QoL alive after 6 months of randomisation	60.9 (20.9) (n=66)	64.3 (19.9) (n=63)	-	-
Mean (SD) GHS QoL in those who died within 6 months of randomisation	46.4 (21.4) (n=7)	38.9 (30.6) (n=12)	3.9 (-2.8 to 10.7)**	0.25
* adjusted for baseline score; ** post hoc analysis SPC = specialist palliative care; SD = standard deviation; CI = confidence interval; GHS = Global Health Status (from EORTC QLQ–C30; higher score – better QoL); GHQ = General Health Questionnaire (higher score - higher depression/anxiety)

Conclusion:
Provision of early palliative care for all patients with recently diagnosed MPM is not associated with beneficial changes in quality of life as compared to palliative care review based on symptom burden.

Background:
Our group has developed a new approach focusing on Surgery for Mesothelioma After Radiation Therapy (SMART), with encouraging results in a phase I/II clinical trial. The impact on the immune system of high-dose hypofractionated radiation therapy is expected to open the door for new combination therapy of immunotherapy and radiation to optimize their synergism on the immune system. The aim of this study is to investigate the antitumor effect of non-ablative hypofractionated radiation combined with anti-CTLA-4 antibody (a-CTLA-4) or low-dose cyclophosphamide (LD-CTX) in murine malignant mesothelioma model.

Method:
Balb/c mice were subcutaneously injected with murine mesothelioma AB12 cells into the left flank on day 0 (primary tumor) and into the right flank on day 7 (secondary tumor). Local radiotherapy (LRT) 5 Gy was delivered to primary tumor once daily for 3 consecutive days (total dose: 15 Gy). Mice were randomized into six groups: (1) No treatment, (2) LRT, (3) a-CTLA-4, (4) LRT+a-CTLA-4, (5) LD-CTX, (6) LRT+LD-CTX. We assessed local and abscopal effects by measuring primary and secondary tumor growth. Furthermore, CD4+ and CD8+ T cell proportion in tumor, spleen and peripheral blood were determined by flow cytometry.

Result:
Mice treated with LRT+a-CTLA-4 and LRT+LD-CTX showed the most significant deceleration in primary tumor growth compared to the other 4 groups. Both combination groups showed similar antitumor effects on the primary tumor. The secondary tumor growth tested the abscopal effect tended to be decreased in mice treated with LRT and LRT+a-CTLA-4 or LRT+LD-CTX compared to untreated mice, but the difference was not significant. Quantification of tumor-infiltrating T cells by flow cytometry showed that the percentages of total T cells, and CD4+ and CD8+ T cells in the primary tumor were increased in the combination groups.

Conclusion:
Combination of LRT and immunotherapy showed synergistic antitumor effects in controlling irradiated-tumor growth. CTLA-4 blockade and LD-CTX might be good candidates in combination with radiotherapy.

Background:
Encouraging survival has been reported with pleurectomy decortication (PD) for malignant pleural mesothelioma (MPM) in several surgical case series. However, doubts remain over the degree of selection bias that constitutes the final composition of these series which therefore lead to questions surrounding the validity of the reported outcomes. We have reviewed our initial experience in the MARS 2 study to analyse this surgical selection process in more detail.

Method:
The MARS 2 pilot is randomised trial of RCT of 14 UK centres recruiting into a cisplatin/pemetrexed with or without the addition of PD for meseothelioma in those who remain suitable after an induction two cycle regime. We completed the pilot to analyse screening, eligibility, consent and randomisation data to estimate the eventual pool of patients considered suitable for surgery.

Result:
From 19 Jun 2015 to 5 Dec 2016, 331 patients were screened from the participating centres. In total, 254 patients were excluded, 176 for failed screening and 78 who declined participation. Of the 176, who failed screening the reasons were non resectable disease (74), poor performance status (24), not fit for surgery (4), not mesothelioma (6), death (5) and other (63). From the 331 screened participants, 77 were enrolled to and received the initial two cycles of chemotherapy and a further 21 withdrew. The reasons for withdrawal were declining randomisation (5), progressive disease (10) and other reasons (6), leaving 56 participants randomised into the trial.

Conclusion:
Screening data of a prospective randomised trial (MARS 2) has provided a unique insight into the detailed selection process for PD for MPM. Exclusions occurred at multiple points in the pathway but these have identified potential points for intervention in patient education, staging and fitness assessment and the proportion of tumour progression which will inform the forthcoming phase III study. The clear extent of possible selection bias underscores the importance of evaluating the efficacy of surgery within the context of this randomised trial to be able derive robust estimates of treatment effect.

Abstract not provided

Background:
TET have been associated with autoimmune disorders (AID) in up to 30 % of patients. However, there have been wide variations in the reported prevalence of TET associated disorders based mostly on small single center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. Using our database, we aimed to describe the prevalence of AID in a large French population with TET.

Method:
RYTHMIC database prospectively includes all consecutive patients with a diagnosis of TET discussed in our national tumor board. We calculated the prevalence and described epidemiologic, clinical and pathological characteristics of patients with TET’s related autoimmune diseases.

Result:
From January 2012 to May 2017, 1693 patients were included in the registry. Of these, 200 patients (11.8%) had autoimmune disorder. The mean age at diagnosis of TET was 54 years old and 52% were male. 149 had myasthenia gravis (75.3%), 15 Good syndrome (7.6%), 14 pure red cell aplasia (7.1%), 12 systemic erythematous lupus (6.1%) and 12 thyroiditis (6.1%). Some patients (14.5%) eventually developed more than 1 AID. Diagnosis of AID was mostly done at the same time of TET diagnosis (54.6%) but some patient had their AID diagnosed before (19.8%) or during follow up (13.4%). Masaoka Koga stages were overall well balanced with 16.5% stage III, 16% stage IIb, 13.5% stage I, 13% stage IIa and IV. Histologic subtype distribution was in order of frequency; B2 (37%), AB (14.5%), B3 (14%), B1 (10.5%), thymic carcinoma (4.5 %) and A (4%).

Conclusion:
In our registry of TET, the prevalence of autoimmune diseases was 11.8% and most diagnosis were established at the same time as TET. The extent of disease, measured by Masaoka Koga staging, does not seem correlated.

Background:
Thymic epithelial tumours (TETs) are rare and under-researched intrathoracic cancers. So far the only significant finding is a recurrent (43%) missense mutation in GTF2I. In addition to validating this finding, we set out to expand our understanding of the molecular changes underlying TETs through whole exome sequencing (WES) and detection of copy number alterations (CNAs) following SNP genotyping.

Method:
WES was performed on 17 TETs (2AB, 1B1, 3B2, 2B3, 6CA and 3NETT) and matched normal tissue. Somatic single nucleotide variants (SNVs) were identified with the GATK HaplotypeCaller and annotated for impact prediction (SnpEff 3.6b and SnpSift 1.3.4b) and population frequency (SnpSift 1.3.4b). The frequency of the GTF2I mutation was assessed with Sanger sequencing with semi-nested primers on DNA from 144 TETs of all subtypes. SNP genotyping was performed on 100 TETs of all subtypes with matched normal tissue in most cases, to identify somatic CNAs. Analysis was performed with ASCAT (v2.4.4) and copy number segments were annotated with Bedtools (v2.26.0).

Result:
WES confirmed a low mutation burden for TETs. No highly recurrent mutations were found. Hotspot mutations in NRAS and KRAS were seen, as was a hotspot mutation in TP53 in a NETT. A high impact frameshift MSH6 somatic mutation was noted in one of the squamous cell carcinomas (SCCs). Another SCC had a germline BAP1 mutation and a family history of other cancers, suggesting a BAP1 familial cancer predisposition syndrome in this individual. The GTF2I mutation was seen in 48 of 141 evaluable TETs (34%) and was present more commonly in type A (90%) and AB (69%) thymomas. The frequency decreased to 16%, 6% and 13% in B1, B2 and B3 thymomas respectively and was not seen in any squamous (0/12) or neuroendocrine carcinomas (0/6). Overall, the most frequent copy number gains in TETs involved chromosomes 7q (22%), 1q (17%) and 11q (17%). The commonest gain was in a gene not previously found to be amplified in solid tumours. The most frequent copy number losses were in chromosomes 6p (40%), 2q (37%) and 7q (32%). Gains and losses demonstrated distinct patterns between aggressive versus indolent subtypes.

Conclusion:
The mutation in GTF2I remains the single most frequently recurrent mutation in TETs. We are in the process of establishing a clinical use for this finding. Results from WES and CNA through SNP genotyping have provided important insight into other potential key players in the aetiology of this intriguing malignancy.

Background:
The mainstay of treatment for thymoma is surgery with neoadjuvant chemotherapy recommended to patients with locally advanced disease. EGFR is overexpressed in thymoma. Clinical responses to single-agent cetuximab have been reported in patients with advanced cetuximab. We conducted this two-site prospective phase II trial of cetuximab combined with a standard induction chemotherapy regimen of cisplatin, doxorubicin and cyclophosphamide (PAC) in patients with locally advanced thymoma prior to surgical resection.

Method:
Patients with clinical Masaoka stage III-IVA thymoma were treated with cetuximab (250mg/m[2] weekly x 4 weeks) followed by cetuximab (250 mg/m[2] weekly) combined with cisplatin (50mg/m[2]), doxorubicin (50 mg/m[2]) and cyclophosphamide (500mg/m[2]) 3 weeks x 4 cycles). Radiographic response was assessed by CT using RECIST 1.1 and FDG-PET using PERCIST. All patients went on to surgery after completion of induction therapy. The primary endpoint was major pathologic response (MPR, >90% treatment effect). Planned enrollment was 18 patients in first stage of a two stage design. If 1 MPR was observed, then enrollment would expand to 28 patients.

Result:
Eighteen patients were enrolled: 8 women, median age 53 (range 32-73). WHO Histologic subtype A: 2, AB: 3, B1: 3, B2: 7, B3: 3. Final Masaoka stage I: 2, II: 2, III: 5, IVA: 9. There were no responses to cetuximab alone by RECIST criteria, although 1 patient had a 25% reduction in indicator lesions. Response rate (CR+PR), in evaluable patients after complete treatment course was 50% (8/16, 95% CI 28-72%). Partial responses by PERCIST criteria were seen on PET in 11/18 (61%) evaluable patients. There were no MPRs. R0 resection was obtained in 7 patients; 5 had R1 and 6 had R2 resections.

Conclusion:
The addition of cetuximab to PAC chemotherapy did not lead to pathologic complete responses in the neoadjuvant setting. Cetuximab alone appears to have little effect during 4 weeks of treatment. There was no apparent increase in radiographic response rate with the addition of cetuximab to PAC chemotherapy compared to historical series.

Background:
No standard treatment exists for patients with thymic epithelial tumor (TET) who progress after platinum-containing chemotherapy. We conducted a phase II study of pembrolizumab in patients with refractory or relapsed TET to evaluate the efficacy and safety.

Method:
Between March 2016 and June 2017, patients with histologically confirmed TET who progressed after at least one platinum-containing chemotherapy were eligible. Patients were excluded if they had an active autoimmune disease requiring systemic treatment within the past one year or documented history of clinically severe autoimmune disease. Patients received 200mg of pembrolizumab intravenously every 3 weeks until tumor progression or unacceptable toxicity. Response was assessed every 9 weeks by investigator. The trial was registered with ClinicalTrials.gov, number NCT02607631.

Result:
Thirty-three patients were enrolled, 26 with thymic carcinoma and 7 with thymoma. 19 (57.3%) patients received two or more prior lines of systemic chemotherapy. Median number of cycles was 8 (ranges, 1-22) and median follow-up was 11.8 months (ranges, 1.6-14.9 months). Of 33 patients, eight (24.2%) achieved partial responses, 17 (51.5%) stable disease, and 8 (24.2%) progressive disease as best response, resulting in overall response rate of 24.2% (7 confirmed PR). The median progression-free survival was 6.1 months for both of thymoma and thymic carcinoma. The most common adverse events of any grade include dyspnea (11 [33.3%] of 33 patients), chest wall pain (10 [30.3%]), anorexia (7 [21.2%]) and fatigue (7 [21.2%]). Treatment-related adverse events ≥ grade 3 associated with immune related adverse events (irAE) include hepatitis (4 [12.1%]), myocarditis (3 [9.1%]), myasthenia gravis (2 [6.1%]), thyroiditis (1 [3.0%]), ANCA-associated rapidly progressive glomerulonephritis (1 [3.0%]), colitis (1 [3.0%]), and subacute myoclonus (1 [3.0%]) except anemia (1 [3.0%]). Eight (24.2%) patients (5 thymoma, 3 thymic carcinoma) discontinued study treatment due to irAE, whereas irAEs were manageable with immediate administration of high dose corticosteroid and other immunosuppressive agents in most of patients (7 of 8 [87.5%]). In 18 (54.5%) patients who had tumor specimens available for correlative biomarker analysis, all of four patients achieved partial response had 50% or more proportion score of PD-L1 immunostaining and higher PD-L1 RNA expression compared with non-responders (p=0.0471).

Conclusion:
Pembrolizumab showed promising antitumor activity in patients with refractory or relapsed TET. Given the relatively high incidence of irAEs especially in thymoma, early detection and management of autoimmune toxicity is essential to ensure feasibility of pembrolizumab treatment in patients with TET.

Abstract not provided

Background:
Paragangliomas (PGLs) are rare neuroendocrine neoplasms arising from paraganglia of the autonomic nervous system. Only about 2% of all PGLs are found in the mediastinum; therefore they are not thoroughly investigated. Our study aims to characterize the clinicopathologic, immunophenotypic and genetic features of mediastinal PGLs.

Method:
Surgical files of Mayo Clinic Rochester and an institutional database (1973-2015) were searched for mediastinal PGLs. Thirteen patients were previously reported (Brown ML et al, Ann Thorac Surg 2008). All cases were reviewed by a thoracic pathologist to confirm the diagnosis. Immunohistochemistry was performed using antibodies to SDHB, Ki-67, ATRX, p53, PD-L1 (clone SP263) and ASCL1. Ki-67 labelling index (LI) was calculated as the mean percent Ki-67-positive cells per 3 HPF. Next generation sequencing (NGS) used a 50-gene neuro-oncology panel. Clinical data were retrieved from medical records. Statistical analysis was performed.

Result:
Twenty-four patients with mediastinal PGLs (7 men, 29.2%) had a median age at time of surgery of 44.6 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected, 3 had an incomplete resection. The median tumor size was 5.1 cm (1.6-14). The median Ki-67 LI was 4.1% (0.5-29.7). PD-L1 was expressed in 10% (n=2), 1% (n=4) or 0% (n=17) of tumor cells. ASCL1 was focally expressed in 2 of 23 (8.7%) cases. Diffuse loss of SDHB expression was seen in 17 of 22 (77.3%) cases. ATRX was expressed in all 22 cases tested, but its expression was patchy in 1 case that showed ATRX duplication by NGS. NGS, performed in 19 cases, revealed a single pathogenic mutation in 10 cases including SDHB (n=3), SDHD (n=6) and ATRX (n=1); and two or more mutations in 2 cases including SDHC+TERT (n=1) and SDHB+ATRX+TP53 (n=1). Two additional patients were found to have an SDHB mutation. Ten of 21 patients with available SDHx mutation status (47.6%) had no SDHx mutation. Median follow up, available in 21 patients, was 4.7 years (0.8-11.5). Five patients (2 of which with SDHx mutation) developed metastases and/or recurrence; 4 patients (2 without SDHx mutation, 2 with unknown SDHx mutation status) died (1 perisurgically, 3 of unknown cause at 2.3, 5.8, and 10.6 years after surgery each). Statistical analysis of clinicopathologic features based upon SDHx mutation could not be performed due to the small number of cases.

Conclusion:
Our study demonstrates that the majority of mediastinal PGLs harbors an SDHx gene mutation. Alterations in ATRX gene might represent another genetic event in mediastinal PGLs.

Background:
Nomogram has demonstrated its capability in individualized survival estimates. Some nomogram studies on esophageal squamous cell carcinoma (ESCC) have been reported, but accuracy of those nomograms is not high enough. Also, the role of ESCC nomogram in adjuvant chemotherapy remains unclear. Therefore, clinicopathological prognostic nomogram was developed and validated for patients with ESCC in this study. Its role in personalized adjuvant chemotherapy was investigated as well.

Method:
Data were retrieved about 1042 ESCC patients undergoing right transthoracic radical esophageactomy at Sun Yat-sen University Cancer Centre from January 1997 to December 2013. Of 1042 patients, 886 without adjuvant chemotherapy were divided into training set (Group A, n=590) and validation set (Group B, n=296) in a 2:1 ratio. Group C (the remaining 156 patients with adjuvant chemotherapy plus Group B, n=452) was used to evaluate the role of nomogram in personalized adjuvant chemotherapy. Cut-off points of continuous variables were established by X-tile. Survival and univariate analyses were calculated by Kaplan–Meier method. R software and "rms" package were used to perform Cox proportional hazard (CPH) regression model, plot nomogram, compute C-index, compare models, validate model, and plot calibration curve. The "survivalROC" package was used to plot time-dependent receiver operating curve (ROC).

Result:
The 1-, 3- and 5-year overall survival (OS) for the entire cohort was 88.3%, 64.5% and 54.8%, respectively. Univariate analyses were performed for 13 potential clinicopathological factors. Significant variables were analyzed for CPH regression model using R software and “rms” package. A prognostic nomogram including 8 factors (grade, location, T, N, resected negative nodes, length, gender, drinking history) was developed. C-index of the model was 0.739 (95% CI 0.719-0.759), higher than that of the 7[th] TNM staging system (0.696, 95% CI 0.676-0.716), p < 0.001. The calibration curve and time-dependent ROC showed this nomogram was superior to the 7[th] TNM staging system. The cut-off of prognostic score was 160, by which we grouped patients into low and high prognostic risk subgroup. In Group C, 209 patients belonged to high prognostic risk subgroup. Among them, patients receiving adjuvant chemotherapy had longer OS (p = 0.035). The remaining 243 patients belonged to low prognostic risk subgroup. Adjuvant chemotherapy didn’t improve OS (p = 0.799) in this subgroup.

Conclusion:
An accuracy clinicopathological prognostic nomogram was developed and validated for ESCC patients undergoing right transthoracic radical esophagectomy. The nomogram provided individual prediction of survival. Risk group stratification based on nomogram prognostic score successfully guided personalized adjuvant chemotherapy for ESCC patients.

Abstract not provided

Abstract:
Immunotherapy has become a large part of care for patients with lung cancer and has a very different side effect profile than what Allied Health Care Professionals are use to managing. To that end, the nursing and allied health care research committee of IASLC has developed Immunotherapy Side Effect Guidelines to assist the AHCP in assessing and managing their patients on immunotherapy. This presentation will review these guidelines and discuss implementation in the treatment setting.

Abstract:
This presentation will outline the rationale, role and evidence supporting pulmonary rehabilitation for people with lung cancer. Lung cancer is associated with high disease burden and physical hardship. Individuals with lung cancer experience complex symptoms, which can include dyspnoea, fatigue and pain. These frequently lead to a cycle of inactivity and functional decline. Individuals with lung cancer are less physically active than similar aged healthy peers at time of diagnosis, with less than 40% meeting the physical activity guidelines [1]. Following diagnosis, physical activity levels are lowest whilst patients undergo treatment and do not recover back to pre-treatment levels within six months [1]. Progressive functional decline occurs over this time, with reduction in exercise capacity and muscle strength [1]. In lung cancer, reduced exercise performance is associated with poorer functional independence, worse cancer treatment tolerability and higher all-cause mortality [2]. People with lung cancer, who are less physically active, have worse symptoms, and poorer exercise capacity and health-related quality of life (HRQoL) compared to those who are more active [1]. There is a strong need for pulmonary rehabilitation for this patient group [3]. There are well-established guidelines regarding exercise for people with cancer [4]. The guidelines state that people with cancer should engage in 30 minutes of moderate intensity physical activity on five or more days of the week and muscle strengthening exercises at least twice a week. This is supported by research which demonstrates that exercise is associated with improved exercise capacity, physical function, muscle strength, HRQoL, symptoms and depression in many cancer types [4]. The evidence for pulmonary rehabilitation specifically in non-small cell lung cancer (NSCLC) is growing rapidly [3, 5, 6]. Studies consistently demonstrate that pulmonary rehabilitation and exercise training is safe in lung cancer [3]. Pulmonary rehabilitation can be applied at any stage along the disease spectrum. The majority of evidence currently exists in the pre- and post-operative settings, however there is now growing evidence for pulmonary rehabilitation in advanced stage disease [3]. Prehabilitation is exercise training delivered before treatment. This is a relatively new concept in lung cancer. A recent Cochrane review [5] of exercise training for patients before surgery for NSCLC, included five randomised controlled trials (RCTs), and found pre-operative exercise training compared to usual care (no exercise) was associated with a 67% reduced risk of patients developing a postoperative pulmonary complication, fewer days that patients needed an intercostal catheter (mean difference MD -3.33 days, 95%CI -5.35 to -1.30); shorter post-operative hospital stay (MD -4.24 days, 95%CI -5.43 to -3.06) and improvement in exercise capacity (6-minute walk test MD 18.23m, 95%CI 8.50 to 27.96 m). Recently Licker and colleagues found that preoperative high-intensity interval training and resistance training improved exercise performance, as compared with an exercise and lifestyle advice group who experienced deterioration in exercise capacity while waiting for surgery [7]. The Cochrane review concluded the overall quality of evidence is low and more high-quality trials are needed [5]. Pulmonary rehabilitation following treatment with curative intent is associated with improvements in exercise capacity, muscle function and fatigue [3]. The Cochrane review of exercise training after lung resection included three RCTs, and found significant improvements in exercise capacity in favour of the intervention compared to usual care (no exercise) (6-minute walk test MD 50m, 95% CI 15 to 85) [6]. More recently, Edvardsen and colleagues found a 20-week high intensity endurance and resistance training program compared to usual care, commencing 5-7 weeks post-operatively, was associated with improved exercise capacity, quadriceps muscle strength and mass, and physical function [8]. There is less evidence published to date on pulmonary rehabilitation in advanced disease, however the early evidence suggests that exercise may be effective at increasing exercise capacity, function and HRQoL, and reducing symptoms [3] There are a number of current RCTs in progress at the moment specifically investigating exercise in inoperable or advanced lung cancer. The specific exercise training prescription in lung cancer has varied in the studies completed to date. It is likely that a combination of aerobic and resistance training is required for maximum effect to target both skeletal muscle function and cardiorespiratory fitness; both of which contribute to poor exercise performance in lung cancer [9]. Similarly, the duration of programs (weeks to months) and delivery (inpatient, outpatient, home based) has varied. Further research is required to confirm the optimal timing, prescription and delivery of pulmonary rehabilitation for people with lung cancer. In most countries, pulmonary rehabilitation is not currently part of routine clinical practice for people with lung cancer. As the evidence base grows our next challenge is to translate findings into clinical practice [10]. 1. Granger, C., et al., Low physical activity levels and functional decline in individuals with lung cancer. Lung Cancer, 2014. 83(2):292-299. 2. Jones, L.W., et al., Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer. Lung Cancer, 2012. 76(2):248-252. 3. Granger, C., Physiotherapy management of lung cancer. Journal of Physiotherapy, 2016. 62(2):60-67. 4. Schmitz, K., et al., ACSM roundtable on exercise guidelines for cancer survivors. Medicine Science Sports Exercise, 2010. 42(7):1409-1426. 5. Cavalheri, V. and C. Granger, Preoperative exercise training for patients with non-small cell lung cancer. Cochrane Database of Systematic Reviews, 2017(6). 6. Cavalheri, V., et al., Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer. Cochrane Database of Systematic Reviews, 2015(7). 7. Licker, M., et al., Short-Term Preoperative High-Intensity Interval Training in Patients Awaiting Lung Cancer Surgery: A Randomized Controlled Trial. J Thorac Oncol, 2017. 12(2):323-333. 8. Edvardsen, E., et al., High-intensity training following lung cancer surgery: a randomised controlled trial. Thorax, 2015. 70(3):244-250. 9. Burtin, C., et al., Lower-limb muscle function is a determinant of exercise tolerance after lung resection surgery in patients with lung cancer. Respirology, 2017. 22(6):1185-1189. 10. Granger, C.L., et al., Barriers to Translation of Physical Activity into the Lung Cancer Model of Care. A Qualitative Study of Clinicians' Perspectives. Ann Am Thorac Soc, 2016. 13(12):2215-2222.

Abstract:
While lung cancer care internationally is spoken about in terms of being multidisciplinary, how far does this go in practice, to having comprehensive multidisciplinary involvement of all appropriate medical, nursing and allied health professionals as part of standard lung cancer care? There are an increasing number of allied health professionals internationally who specialise in oncology, with an increase in the evidence base for interventions. I propose that the involvement of allied health professionals as part of standard lung cancer care will lead to improved comprehensive multidisciplinary care, with improved quality of life and function for people living with a lung cancer diagnosis. The core allied health professions include occupational therapy, physiotherapy, exercise physiology, dietetics, speech pathology, social work and psychology. Some countries have other professions that fit into the allied health disciplines, such as physician’s assistant and respiratory therapist. This presentation will focus on the disciplines found primarily in Australia and the UK. Occupational Therapy focuses on enabling ongoing participation in chosen everyday activities. In curative treatment, the occupational therapist has a key role in pre-habilitation, assisting the individual to reach optimum function prior to treatment, and rehabilitation following treatment, to facilitate the persons return to previous chosen and meaningful roles. In metastatic disease, the occupational therapist focuses on enabling continued participation in chosen and meaningful roles. In the acute hospital setting the focus is often on what functional level the individual needs to be at to be able to safely manage the tasks of personal care, meal preparation and other personal and community activities of daily living at home following discharge. While these aspects of function are important, it is key to allow the person living with lung cancer to identify the roles and tasks that they find meaningful and important to participate in. A person may choose to have community assistance with personal care and meal preparation, as this ensures they have the energy to participate in activities that lead to improved engagement and quality of life. Physiotherapy is concerned with identifying and maximising quality of life and movement potential in the areas of promotion, prevention, treatment/intervention, habilitation and rehabilitation[1]. Physiotherapists have a key role in working with people living with lung cancer prior to and following their treatment for lung cancer. There is a growing body of evidence that suggests exercise following treatment for lung cancer is associated with improvements in physical and psychological outcomes[2]. Exercise physiologists are newer members of the lung cancer multidisciplinary team. In Australia, we are seeing as increasing use of exercise physiologists in the private hospital and pulmonary rehabilitation setting. Their role is of smaller scope than physiotherapists, focusing on prescribing and supervising exercise programs to improve exercise capacity, with the aim of improving function and quality of life. Dieticians are key members of the lung cancer team, however they are often not embedded within the multidisciplinary team. Given that cancer cachexia is a common symptom in lung cancer, affecting functional status, treatment tolerance and survival[3] we should be seeing an increase of dieticians within the lung cancer multidisciplinary team internationally. Speech pathologists provide expert assessment and treatment of swallowing and communication disorders. There is a growing body of evidence in the treatment for head and neck cancer, however there is currently no published speech pathology research in the lung cancer space. People living with lung cancer may require the specialist input of a speech pathologist due to dysphagia, as a result of treatment or disease, or speech difficulties caused by brain metastasis. Social Work and Psychology are key members of the lung cancer multidisciplinary team, as studies have demonstrated the prevalence of distress in lung cancer patients to be high[4,5]. All lung cancer patients should have their psychosocial needs regularly screened, with appropriate referrals for support made to ensure these needs are met. Psychologists and social workers need to be embedded within the lung cancer multidisciplinary team to ensure appropriate screening and intervention of patients. Lung cancer multidisciplinary teams need to utilise their allied health professionals to ensure comprehensive care is offered, and received, by patients who are living with a lung cancer diagnosis. There is a paucity of evidence and research into allied health interventions that may benefit people living with lung cancer. It is critical that allied health professionals build on the evidence and continue to research the efficacy of interventions used to optimise quality of life and function for people living with lung cancer. References: WORLD CONFEDERATION OF PHYSICAL THERAPY 2011. Policy statement: Description of physical therapy. World Federation of Physical Therapy. GRANGER CL 2016. Physiotherapy management of lung cancer. Journal of Physiotherapy, 62, 60-67. PERCIVAL C, HUSSAIN A, ZADORA-CHRZASTOWSKA S, WHITE G, MADDOCKS M & WILCOCK A 2013. Providing nutritional support to patients with thoracic cancer: Findings of a dedicated rehabilitation service. Respiratory Medicine, 107, 753-761. STEINBERG T, ROSEMAN M, KASYMJANOVA G, DOBSON S, LAJEUNESSE L, DAJCZMAN E, KREISMAN H, MACDONALD N, AGULNIK J, COHEN V, ROSBERGER Z, CHASEN M & SMALL D 2009. Prevalence of emotional distress in newly diagnosed lung cancer patients. Support Care Cancer, 17, 1493-1497. ZABORA J, BRINTZENHOFESZOC K, CURBOW B, HOOKER C & PIANTADOSI S 2001. The prevalence of psychological distress by cancer site. Psycho-Oncology, 10, 19-28.

Abstract:
Beyond the basics: The status and future directions of mesothelioma treatments Background: While prognostic factors for pleural and peritoneal mesothelioma have been investigated over the last decade, the characterization of molecular alterations in pleural mesothelioma may lead to a better understanding of tumorigenesis and targeted chemotherapeutic treatments for these tumors. In a recent study examining mutation burden outcome of non-small cell lung cancer, Rizvi et al. found that smokers had more mutations, correlated higher mutation load, and better clinical outcome to immune-targeted therapies than non-smokers. This has yet to been fully elucidated for MPM. Method: A systematic review of literature published from October 2009 – July 2017 was done using PubMed. Discussion: Various studies have shown patients with a history of smoking and asbestos exposure have a greater mutation burden than non-smokers. Despite non-small cell lung cancer studies suggesting that patients with greater mutational burden have better clinical outcomes to immune-targeted therapies, this population of MPM patients typically is excluded from these trials. To date there has not been a study showing that MPM patients with multiple malignancies should be precluded from participating in immunotherapy trials. Participatory groups in immunotherapy must be reshaped to include this subset of MPM patients to better grasp the role that multiple malignancies play with regards to appropriate treatment measures. It is notable that several large mesothelioma trials have not successfully made it pass Phase 2. This suggests that the correct population has not been identified. Perhaps early data showing promising results are merely a synergistic effect between study agents and tumor burden and should be reconsidered. Rather than potentiating study agents effects, increased tumor burden may be an independent factor in patient response. Conclusion: Elucidation of the role of tumor burden may improve the effectiveness and utility of novel MPM which retains its attractiveness despite the current sparse and narrow body of supporting data. Instead of observing treatment by individual case, there must be a shift in treatment observation to account for populations of similar characteristics (i.e. multiple malignancies). With no cure for mesothelioma on the horizon, evaluating the study populations will be imperative to understanding the effectiveness of these new treatments.

Abstract not provided