Virtual Library

Background:
Lung cancer (LuCa) has been the most common cancer in the world for several decades and also the most common cause of death from cancer worldwide. Immunotherapy, for induction of tumor cell specific immune responses destroying tumor cells, has emerged as a promising treatment modality in solid malignant tumors. Studies have shown that chemotherapy can be combined with vaccine without impairing the immune response.

Methods:
SLU01 is a randomized, open, parallel-group, multicenter, international phase I/II study to evaluate the efficacy and safety of DCVAC/LuCa (active cellular immunotherapy based on dendritic cells) added to standard first line chemotherapy with carboplatin and paclitaxel +/- immune enhancers (interferon-α and hydroxychloroquine) vs chemotherapy alone in patients with Stage IV NSCLC. The study was initiated in December 2014 and plans to enroll 105 patients at approximately 12 sites in Czech and Slovak Republics. Eligible patients are required to present with metastatic NSCLC defined by histologically or cytologically confirmation and ECOG score 0-1. All patients will receive Standard of Care (SoC) carboplatin and paclitaxel, and will be randomized 1:1:1 to DCVAC/LuCa or DCVAC/LuCa + immune enhancers (pegylated IFN-α2b and hydroxychloroquine) or SoC only. Patients will be stratified by histology subtype adenomatous or squamous cell carcinoma and smoking history. The primary objective is to compare efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone in patients with stage IV NSCLC, as measured by progression free survival (PFS). Secondary objectives include assessments of safety, objective response rate (ORR), duration of response (DoR) and overall survival (OS). Exploratory objectives include comparison of changes in immune responses and search for prognostic biomarkers. Clinical trial information: EudraCT number 2014-003084-37.

Results:
Section is not applicable

Conclusion:
Section is not applicable

Background:
PM01183 (lurbinectedin) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. Synergism in combination with doxorubicin with compelling overall response rates (~67%, including approximately 10% complete responses) was reported in a phase I expansion cohort in 21 second-line SCLC patients (pts) (ASCO 2015, abstract 7509). The most common toxicity observed was hematologic.

Methods:
Multinational, multicenter (>150 sites), open-label, randomized, phase III study of PM01183/doxorubicin vs. a control arm with investigator choice of either standard CAV or topotecan (1.5 mg/m[2], D1-5 q3wk). A total of 600 pts will be randomized (1:1) and stratified according to ECOG performance status (PS), chemotherapy-free interval (CTFI), known CNS involvement, prior PD-1/PD-L1 based immunotherapy and potential investigator’s control preference. Patients with clinical benefit after 10 cycles of doxorubicin containing-combination will continue on single agent PM01183 or CV, until PD or unacceptable toxicity. Interim safety analysis will be performed after 150 pts by an independent data monitoring committee. The most relevant inclusion criteria are: pts ≥18 years old; confirmed diagnosis of SCLC (small-cell carcinomas from unknown site are eligible provided ≥50% Ki-67 expression). One prior platinum containing regimen is mandatory (additional immunotherapy is allowed provided that it was not given in combination with CT); PS: 0-2 and adequate major organ function, including normal LVEF ≥50% at baseline. Pts are excluded if pre-treated with PM01183, doxorubicin or topotecan; symptomatic or steroid requiring CNS involvement or any serious medical condition that might preclude safe compliance with study treatment. The primary objective is to determine a difference in progression-free survival by an independent review committee. Secondary endpoints are overall survival, survival rates at 12/18/24 months, antitumor response (RECIST v1.1), duration of response, QoL, safety, subgroup analyses and pharmacokinetics (PK) of PM01183/doxorubicin arm. First patient is planned in JUL2016. Enrollment is expected to be completed by 4Q17.

Results:
Section not applicable

Conclusion:
Section not applicable

Background:
It has been theorised that local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) could improve outcomes for patients with oligometastatic disease. There is now growing evidence to support the safety, local control effect and potential improvement in overall survival (OS) for SABR/SRS to warrant a randomised phase III trial. The SARON trial investigates the impact on OS of radiotherapy (RT) plus SABR/SRS following standard chemotherapy in patients with oligometastatic NSCLC and will undertake an early evaluation of feasibility and toxicity.

Methods:
SARON is a randomised, multicentre, phase III trial for patients with oligometastatic NSCLC (1-3 sites of synchronous metastatic disease). An early feasibility review will take place after 50 randomised patients. Patients requiring both conventional thoracic RT to the primary and SABR to a thoracic metastasis will be included in a sub-study to more thoroughly assess toxicity and planning issues. 340 patients will be recruited from 30 UK sites, to randomise 306 patients (1:1) to receive either platinum doublet chemotherapy alone (control arm) or platinum doublet chemotherapy followed by radical RT/SABR to their primary tumour and then SABR and/or SRS to all other metastatic sites (investigational arm). Figure 1



Results:
The primary endpoint is OS, and the study is powered to detect an improvement in median survival from 9.9 months in the control arm to 14.3 months in the investigational arm (85% power, 5% two-sided alpha). The secondary endpoints include progression free survival, toxicity, local control of primary and metastases, and quality of life.

Conclusion:
The study will open in Q3 2016 and is supported by Cancer Research UK (C13530/A18015).

Background:
Clinical decision making in lung oncology is informed by evidence about the risks and benefits of proposed treatments, alongside other important factors including clinician experience and patient preference. There is no consensus about which outcome measures are most meaningful to patients or informative for clinicians. Measures relating to disease response and survival are common, but it is not known which specific measures are most favoured, how consistently they are defined, and how frequently domains such as quality of life are represented.

Methods:
A systematic review of EMBASE, COCHRANE and MEDLINE was conducted. Prospective studies of radical radiotherapy or chemoradiotherapy for lung cancer published during 2013-2016 were included, where clinically-relevant outcomes (including patient-reported outcomes) were reported. Individual outcomes were recorded and categorised. Frequency of outcomes, reported definitions and consistency of reporting both within and between studies were examined. Study quality was assessed against UK national standards.

Results:
29 papers met the full inclusion criteria. 124 separate outcome measures were reported, within which, 68 distinct outcomes were identified. 47/124 outcome measures were defined or referenced. None were defined consistently between studies. 3 papers described an outcome measure in their Methods but did not report it in their Results. 24/29 papers reported outcomes not introduced in their Methods. One paper included patient-reported outcome measures. No short-term outcome measures (such as 30 or 90 day mortality) were reported.

Conclusion:
This systematic review has highlighted significant variation in practice in outcome measure reporting in studies of radical lung cancer treatments. A large number of different outcome measures were reported, the majority of which weren’t defined. Where apparently identical outcome measures were reported in more than one study, definitions were inconsistent. Outcome measures relating to short-term survival were not reported at all, despite the fact that long-term survival in this patient population was uncommon. Only one study included patient-reported outcome measures. If lung cancer research is to optimally inform clinical decision making, study endpoints should reflect outcomes that are most meaningful to patients and their clinicians. Variation in outcome-reporting practice, particularly where definitions are lacking and inconsistent, is a significant concern. It threatens the ability of clinicians to assimilate the findings from multiple studies and limits the extent to which the true benefits and burdens of proposed treatments can be understood. Consideration should be given as to whether a core outcome set, incorporating clinically meaningful and patient-reported outcomes, might be warranted in lung cancer. Further research is needed.

Background:
Blastomatoid pulmonary carcinosarcoma is a biphasic tumor with a worse prognosis. The differenial diagnosis is pulmonary blastoma and is often challenging.

Methods:
We describe a case of blastomatoid pulmonary carcinosarcoma (BPCS), combined with lepidic adenocarcinoma in a 77-year-old female. Chest computered tomography detected a 7.5cm sized well marginated mass in right upper lobe.

Results:
Microscopically, most of the tumor (80%) revealed an immature glandular epithelium resembling high-grade fetal adenocarcinoma expressing epithelial markers and membranous beta-catenin, and blastomatoid spindle cells with extensive necrosis. Both epithelial and spindle cells expressed p53, but not thyroid transcription factor-1 (TTF-1) and Napsin-A. In focal area (20%), lepidic adenocarcinoma (LA) expressing TTF-1 was also noted. Mutation analysis revealed an EGFR mutation within LA, but, no mutation within BPCS.

Conclusion:
Blastomatoid carcinosarcoma can coexist with lepidic adenocarcinoma. However, mutation status is different between two components.

Background:
In reporting experience from clinical trials for advanced lung cancer, proper presentation of endpoints should support decisions for patient management and offer a basis for further research. This postulate was tested in a survey of published trials.

Methods:
The survey includes reports on trials of systemic treatment of advanced lung cancer published between 2013 and 2015 and included in the PubMed database. After excluding reviews, discussion papers, trials on palliative measures, trials on local treatment, case reports and Phase I clinical trials, 316 reports on a total of 303 trials were identified. Analysis focused on primary and secondary endpoints.

Results:
The analysis includes 124 single-arm Phase II trials, 170 randomised Phase II or Phase III trials and 9 Phase IV trials, with a total of 75.467 patients. Only 31 reports dealt with small-cell lung cancer. The main treatment modalities were cytotoxic drugs (100 trials), targeted drugs alone or in combination with chemotherapy (168 trials) or immunotherapy (21 trials). Median interval form closure of recruitment to publication was 35 months and exceeded 4 years in 24.4% of trials. The following weak points of the reports under survey were identified: Objective response rate (ORR) as the primary endpoint (117 reports), and progression-free survival (PFS) as the primary endpoint (125 reports): 41 of these reports did not include information on interval of evaluation and did not specify confirmation of response; in additional 12, this interval exceeded 8 weeks. Overall survival (OS) as the primary endpoint (49 reports): no information on post-trial treatment in 27 reports. Quality of life (QoL) was the primary endpoint only in 6 trials, and was not reported as secondary endpoint in 79.2 % of all trials. Toxicity: 58.4 % of reports provided very fragmented information and offered no data on the proportion of patients with any grade 3 or greater toxicity.

Conclusion:
The quality of research protocols and of reporting the experience from trials on advanced lung cancer are often sub-optimal. Better design of trial protocols, timely precise reporting and meticulous review of papers submitted for publication are strongly encouraged, so as to offer adequate information for clinical practice and for further research. Considering the importance of QoL for any patient with incurable disease, lack of data on QoL is most embarassing. Information on QoL should be a part of every report; this goal is achievable only with simple, easy-to-use instruments such as EQ-5D-5L self-administered questionnaire.

Background:
Loss to follow-up (FU) is an important issue in survival analysis using the data based on hospital records. To better address the magnitude of this issue in a real clinical setting, we compared survival outcomes from hospital database with those from national cancer registry data which incorporated national vital status record.

Methods:
From the hospital database of National Cancer Center Hospital, Korea, we identified 970 small cell lung cancer (SCLC) patients who were treated between 04/2001 and 04/2013. Most of them were male (n = 854) and smokers (n = 906). Median age was 63 years (range, 32–80 years). We made two survival datasets, hospital-based dataset (HD) and cancer registry-based dataset (CD).

Results:
Of 352 LD-SCLC patients, there were 144 deaths in the HD and 107 additional deaths were identified in the CD (Total= 251). There was no difference in median progression free survival (PFS) between the HD and CD (12.7 months [95% CI, 10.9-14.6] vs. 12.3 months [95% CI, 10.8-14.2]). But, median OS in the HD was significantly longer than in the CD (55.7 months [95% CI, 35.8-115.6] vs. 26.3 months [95% CI, 22.8-30.8]). The 5-year survival rate of LD-SCLC was 48.7% vs. 29.6% in the HD and CD, respectively. For 618 ED-SCLC patients, there were 234 deaths in the HD while 341 additional deaths were confirmed in the CD (Total= 575). Median PFS from the HD was similar to that from the CD (6.5 months [95% CI, 6.2-6.9] vs. 6.4 months [95% CI, 6.1-6.8]). Median OS of HD was 14.5 months [95% CI, 13.5-16.9], significantly longer than that of CD (11.9 months [95% CI, 11.2-12.9]). The 5-year survival rate of ED-SCLC in the HD and CD was 11.5% and 3.5%, respectively. In the simulation analysis, the estimated median OS increased as the proportion of patients who were actually dead but censored in the HD increased. When this proportion was 25%, 50% and 75%, the estimated median OS was 27.8 months, 33.8 months, and 37.2 months for LD-SCLC, respectively, and 12.5 months, 13.1 months, and 13.7 months for ED-SCLC. Obviously, this discrepancy reflects the limitation of HD-based survival analysis since medical records do not trace all patients until death, especially for those who did not return for subsequent follow-up care.

Conclusion:
Incomplete follow-up, by increasing the number of censoring events, could result in spurious prolongation of overall survival, which warrants caution in interpreting the HD-based survival analysis.

Background:
In 2014, the Addario Lung Cancer Medical Institute (ALCMI) launched a prospective study to characterize somatic and germline genomics of adolescents and young adult (AYA) patients under the hypothesis that lung cancer diagnosis at younger ages (<40) are more likely to have targetable genomic alterations. It is estimated that less than 2% of those newly diagnosed with lung cancer globally are AYA, thus presenting a striking recruitment challenge.

Methods:
The study workflow includes a dedicated website enabling e-consenting so patients can participate remotely from anywhere in the world, including the underserved, and employs social media to share our trial. We have an integrated data and bio repository that allows for seamless communication and completion of study activities including routing of blood and tumor specimens. ALCMI's "sister" foundation, the Bonnie J. Addario Lung Cancer Foundation, played a key role in educating patient and caregiver communities, including a social media campaign.

Results:
Accrual opened July 23, 2014. In the first 5 weeks of the study, 37 subjects consented versus the 5 projected. Of the 37 initially consented, 35 enrolled via the remote web-portal. As of June 15 2016, 104 subjects are enrolled (128 consented) in the study from 10 countries following a social media campaign of 89 discrete postings resulting in 21,062 active users out of 391,222 individual viewers and 675,680 impressions. Of the 104 subjects enrolled to date, 49% entered the study via the remote study portal with the balance recruited locally by participating ALCMI study sites. 45% of total accruals to date resulted from the education outreach by patient advocacy and patient to patient social networking.Figure 1



Conclusion:
This study clearly demonstrates the utility, speed and feasibility of remote, web-based screening and consenting platforms supported by patient-centric, advocate-driven social media efforts as novel approaches to "bringing research to the patient" for global clinical trials.

Background:
Traditionally, study results have been presented as abstracts at major scientific meetings at the conclusion of the analysis. Recently, presentations of studies in progress and updates to previously presented data have been allowed at major meetings. The frequency and implications of a single study being presented multiple times, particularly in high profile oral presentations, have not been fully evaluated.

Methods:
To identify studies presented multiple times, abstracts from an approximately one year period from international conferences for three major societies devoted largely or in part to lung cancer research were assessed (ASCO 2015, World Lung 2015, ESMO 2015 and ASCO 2016). Abstracts were selected in a two-step process. The first step was for subject matter based on keywords: NSCLC, SCLC or immunotherapy. Searches differed slightly based on individual website functionality, with ASCO searched by track, World Lung by session and ESMO by individual abstract. In a second step, abstracts for which clinical outcome data was presented from a trial with an identifiable NCT number were selected. Immunotherapy abstracts that did not include the treatment of NSCLC or SCLC were excluded in the second step.

Results:
851 abstracts were identified that were related to NSCLC, SCLC or immunotherapy. Of these, 357 referred to a clinical trial. 110 of 357 (30%) described clinical trials that were presented multiple times (mean 2.75, range 2-7), and in 44 (12%), this occurred at the same conference. 113 of 357 abstracts (31%) were oral presentations. 75 (66%) of the oral presentations presented data from clinical trials that were presented multiple times, including 35 (31%) which were presented as oral presentations at least twice. Of the 16 unique clinical trials leading to multiple oral presentations, a variety of issues led to the duplicate presentations, including different cohorts of the same trial, biomarker analysis, analysis by one study variable, or simply updated data. In total, only 6 of 16 of these studies presented additional patients in a subsequent oral presentation, two presenting unique cohorts, and the other four presenting updated data that included additional patients, in one case, fewer than ten patients.

Conclusion:
There is a pattern of multiple presentations of clinical trials, particularly in oral presentations, at major meetings. Although a second oral presentation on the same concept may sound confirmatory to a conference participant, in most cases, data presented in subsequent oral presentations related entirely to patients whose data was presented in the previous oral presentation.

Background:
Anaplastic lymphoma kinase (ALK) rearrangements with concurrent epidermal growth factor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations occur very rarely. Outcomes with TKI in these patients (pts) are poorly understood.

Methods:
Outcomes of pts with metastatic NSCLC and double mutations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and PCR or NGS (EGFR/KRAS) from six oncology centres in Switzerland were retrospectively analysed.

Results:
A total of 15 pts with adenocarcinoma were identified, 53% were females and tumor stages were IIIB (6%), IVA (27%) and IVB (67%). Six pts had a co-mutation of ALK/EGFR and nine ALK/KRAS. ALK/EGFR pts were younger (54 vs. 64 years) and less likely to be (ex-) smokers (34% vs. 77%). In total, 12 pts received an ALK-TKI (11x crizotinib, 1x alectinib, 2x ceritinib, 1x lorlatinib). EGFR-TKIs were given to five EGFR/ALK pts (4x afatinib, 2x osimertinib, 3x erlotinib). 33% received > 1 ALK-or EGFR-TKI. TKI were given as first-line (1L) in 40% (4x ALK/KRAS, 2x ALK/EGFR). Pts with ALK/KRAS co-mutation: Seven of eight pts (88%) were primary refractory to ALK-TKI treatment (all crizotinib). One patient has ongoing disease stabilization since 26 months. Three of six pts responded to 1L platinum-based chemotherapy with a median progression free survival (PFS) of 4.25 months (range: 1 month - NR). Pts with ALK/EGFR co-mutation: Two of four pts responded to ALK-TKI: one PR to crizotinib+erlotinib combination, one PR to alectinib and lorlatinib. Median PFS on first ALK-TKI was 3.75 months (range: 1-7months). Three of five pts (60%) achieved one or more responses to EGFR-TKI in different lines of therapy (4x PR: 3x afatinib, 1x osimertinib, CR: 1x osimertinib). Median PFS on first EGFR-TKI was 4.5 months (range: 3-7 months). Two of five pts responded to platinum-based chemotherapy (median PFS: 5.5 months (range: 0.25-10 months)).

Conclusion:
De novo concurrent ALK/KRAS alterations are associated with resistance to ALK-TKI treatment in seven out of eight pts, although one patient achieved ongoing disease stabilization for 26 months. Thus, platinum-based chemotherapy should be 1L treatment for these patients. In ALK/EGFR pts outcomes with ALK and EGFR-TKI seem inferior to what would be expected in pts with either alteration. EGFR-TKIs may potentially be more active compared to ALK-TKIs in ALK/EGFR pts. Worse outcomes to ALK-TKI may partly be related to false-positive ALK test results. Further studies are needed to clarify which patients may still benefit from the respective TKI.

Background:
Chemoradiotherapy is the standard treatment for locally advanced squamous cell lung cancer, however, treatment development is urgently needed due to poor prognosis and significant toxicity. Combination therapy of carboplatin and nab-paclitaxel is a useful choice as first-line therapy for patients with advanced non-small cell lung cancer, especially for squamous cell cancer. This prospective phase Ⅱ study was conducted to explore the efficacy and toxicity of concurrent chemoradiotherapy with nab-paclitaxel, carboplatin and thoracic radiotherapy in unresectable locally advanced squamous cell lung cancer.

Methods:
Patients with unresectable Stage Ⅲ squamous cell lung cancer were eligible. Patients received nab-paclitaxel weekly at a dose of 60mg/m[2], in combination with carboplatin (area under the plasma concentration time curve (AUC) 2) weekly during concurrent chemoradiotherapy. Thoracic radiation was administered at a dose of 66Gy/33 fractions, both three dimensional conformal and intensity modulated radiation therapy were allowed. The consolidation phase chemotherapy consisted of full dose nab-paclitaxel (260 mg/m[2] on day 1) and carboplatin (AUC 6 on day 1) every 21 days was administered in two cycles after the concurrent chemoradiotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), acute radiation esophagitis and pneumonitis.(Clinical trial registration: NCT01494415).

Results:
Initially, enrollment of 21 patients was planned; however, the trial was prematurely closed due to slow recruitment. Finally, a total of 8 patients were enrolled between January 2012 and July 2015 from one institute. All patients completed concurrent chemoradiotherapy and 6 patients (75.0%) received consolidation chemoradiotherapy. The objective response rate was 62.5%, with partial remission 5 (62.5%), stable disease 2 (25.0%), progressive disease 1 (12.5%), respectively. After a median follow-up of 11.6 (range, 2.0–29.2) months, 5 patients were dead, 3 were alive. The median progression-free survival and overall survival were 12.1 months and 15.2 months, respectively. According to Common Terminology Criteria for Adverse Events (CTCAE) version.4.0, 6 patients (75.0%) experienced acute radiation esophagitis, 4 (50.0%) were grade 2 (G2), 2 (25.0%) were G3; 4 patients (50%) experienced acute radiation pneumonitis, 3 (37.5%) were G2, 1 (12.5%) were G3. No late radiation-induced esophageal and pulmonary toxicity was observed after 1-year follow-up.

Conclusion:
Concurrent nab-paclitaxel, carboplatin and thoracic radiotherapy is showed to be an effective regimen for patients with unresectable locally advanced squamous cell lung cancer. However, further study should exercise caution due to the severe toxicity of radiation tissue injury especially acute radiation esophagitis.

Background:
Nivolumab (NIV) is approved in several countries for pre-treated patients with advanced non-small cell lung cancer (NSCLC). UK NICE previously reported that NIV is not cost-effective compared with DOC for the treatment of squamous NSCLC. Here, we report cost-effectiveness for nonsquamous NSCLC, and consequences of patient selection by PD-L1 testing.

Methods:
Based on the published results of the CheckMate-057 trial (Borghaei et al, NEJM 2015), we performed a literature-based health economic modelling study to estimate the incremental cost-effectiveness ratio (ICER) of NIV versus DOC for the Swiss health care setting. We estimated the probability of reaching cost-effectiveness based on a willingness to pay (WTP) threshold of CHF100’000 per QALY gained. Moreover, we implemented patient selection for NIV treatment using PD-L1 staining, and modelled the effect of reducing the NIV price, dose, and treatment duration, on the ICER.

Results:
In the base case model, NIV (mean costs CHF 66’208; mean effect 0.69 QALYs) compared to DOC (mean costs CHF 37'618; mean effect 0.53 QALYs) resulted in an ICER of CHF 177’478 per QALY gained. Selecting patients for NIV by PD-L1 testing (threshold ≥10%), resulted in a base case ICER of CHF124’891 per QALY gained, compared to treating all patients with DOC. Reduction of NIV price, dose, or treatment duration, all reduced the ICER partially below an assumed WTP of CHF100’000 per QALY (see Table 1). Cost-effectiveness was strongly influenced by health state utilities. Table 1 Results of the base case and scenario analyses

Scenario	Treatment arm	Cost (mean)	Effect Month (mean)	Effect QALY (mean)	Compared to	Incremental costs	Incremental effect	ICER CHF	probability cost- effective
Base case	DOC	37'618	10.99	0.53
NIV	66’208	15.42	0.69	DOC	28’589	0.16	177’478	14.1%
PD-L1 ≥1%	74'968	17.26	0.79	DOC	35’530	0.27	133’267	19.7%
NIV	6'941	0.11	65’774	85.2%
PD-L1 ≥10%	69’893	16.83	0.78	DOC	32’274	0.26	124’891	22.1%
NIV	3’685	0.10	37’860	86.7%

DOC= docetaxel, NIV=Nivolumab, QALY= quality adjusted life years, ICER= incremental cost effectiveness ratio, CHF=Swiss Francs

Conclusion:
At its current price, NIV is not cost-effective compared with DOC for the treatment of patients with nonsquamous NSCLC. Price reduction and/or patient selection by PD-L1 testing would be highly recommendable from a socio-economic viewpoint.

Background:
With an increase in biomarker-directed therapies, tissue biopsy to identify targetable mutation status will become a mainstay of managing patients with NSCLC. The current study assessed the frequency, complications and costs of initial diagnostic biopsy (IDP) and post-progression biopsy (PPB) given the current limited information.

Methods:
This retrospective, observational study was conducted using administrative claims data from over 30 million commercially insured individuals in the US (2006-2014). Patients with continuous health-plan enrollment ≥12-months prior and ≥3-months post-index (first-observed) NSCLC diagnosis date were included and followed until health-plan disenrollment, study endpoint (December 2014) or death (whichever occurred earlier). Patients with NSCLC (n=20,013) were categorized into 4 groups (IDB only (58%); IDB+PPB (9%); PPB only (1%); and no biopsy (32%)) based on presence or absence of claim(s) for IDB and/or PPB. Biopsy procedures, post-biopsy complications and costs were assessed during the follow-up period. Identification of claims was based on ICD-9-CM diagnosis/procedure and/or HCPCS codes. All analyses were descriptive in nature.

Results:
Study included 20,013 patients (median age: 69 years) with 52% being females, 73% enrolled in a preferred provider organization and 35% managed in Midwest. 10% of the patients had a PPB. Bronchoscopy (IDB 53%; PPB 71%) and percutaneous needle biopsy (IDB 42%; PPB 21%) were the commonly employed biopsy procedures. 63% patients had a medical claim for at least 1-complication within 30-days post IDB for difficulty breathing (41%), severe chest pain (23%) or pneumothorax (14%). 30-day complication rate (61%) was similar among patients with a PPB. Among patients undergoing bronchoscopy higher proportion had medical claim for complications including difficulty breathing (IDB: 44% vs. 37%; PPB: 46% vs. 26%) and hemoptysis (IDB: 14% vs. 4%; PPB: 15% vs. 3%) compared with patients undergoing percutaneous needle biopsy. Average IDB episode costs were significantly higher among patients with a complication compared with patients without a complication (day of biopsy: $12,030 vs. $6,508; within 7-days: $13,657 vs. $7,765; p-value<0.001).

Conclusion:
In this large cohort of NSCLC patients the rate of PPB was 10%. Importantly, for the first time we determined that the rates of complications were similar for the IDB and PPB among patients enrolled in a large national US health plan. With likely increased demands by patients, providers and payers for diagnostics confirmation for biomarker-directed therapies, data from this study will be of value in comparing complications rate and determining budget-impact of newer less-invasive molecular testing methods.

Background:
Changes to national reimbursement criteria in France may limit patient access to pemetrexed. In the absence of head-to-head comparative clinical trials, we compared outcomes for various induction–maintenance (I–M) sequences used in advanced non-squamous (nsq) non-small cell lung cancer (NSCLC) in France. We estimated the impact of not treating with pemetrexed, compared with current French practice, in terms of life-years (LYs) and quality-adjusted life-years (QALYs).

Methods:
Progression-free survival (PFS) and overall survival (OS) of I–M sequences used in French clinical practice were assessed following literature review and network meta-analysis using a sequential decision analytic model adapted for the French healthcare setting. LYs and QALYs (using French EQ5D values) were estimated and compared for sequences with and without pemetrexed. Conservative assumptions were made for missing data. First-line treatment pattern data were taken from the overall European FRAME prospective observational study cohort (Moro-Sibilot. Lung Cancer 2015). The target population for first-line pemetrexed therapy was derived from a French National Authority for Health Pemetrexed Assessment Report (HAS 2016).

Results:
In the base case, the I–M sequence pemetrexed+cisplatin→pemetrexed was associated with the longest median PFS and OS (5.98 and 12.88 months, respectively) and highest LYs and QALYs (1.37 and 0.93, respectively) (Table). LYs and QALYs were higher for all comparators when pemetrexed rather than best supportive care was used as maintenance. By weighting treatment sequences by FRAME treatment patterns, not using pemetrexed in this setting yielded overall losses of 1232–1314 LYs and 922–983 QALYs each year in France. Figure 1



Conclusion:
According to the results of this modelled analysis, compared with current French practice, limiting access to pemetrexed for the I–M treatment of patients with advanced nsqNSCLC could result in substantial loss of LYs and QALYs in this population.

Background:
Increasing costs of novel immunotherapy requires risk sharing between manufacturers and payers. Aside from the cost per dose of the compound, the total treatment cost (TTC) is affected by the duration of treatment (DOT). DOT in real life may differ significantly from that observed in the randomized clinical trials. The objective of this study was to develop a risk sharing strategy based on real world data for the use of nivolumab in NSCLC.

Methods:
We analyzed DOT for 260 consecutive patients with advanced NSCLC treated with nivolumab at five Israeli cancer centers between January 2015 and March 2016. We developed a model to incorporate the number of cycles delivered and to calculate the TTC for each patient. We calculated the “mid-point” (MP) to estimate the number of cycles for all patients to comprise half of the TTC for the population.

Results:
Median age 67y (range 41-99); males 68%; ECOG PS ≥2 46%; Non-squamous (Non-sq)/Squamous(Sq)/other histology 70%/23%/7%; treatment line: 1[st]/2[nd]/3[rd]+-line/NA 6%/64%/26%/4%. All patients received nivolumab as standard of care or within the compassionate use program. Median duration of follow-up was 4.3 mo (range 0.1-13.8); 27% of patients continued the treatment at the time of data cut-off. Median DOT was 2.7 mo (range 0.1-15.5). Median number of treatment cycles delivered calculated from a total of 206 patients was 6 (range 1-26 and 1-23 for Sq and Non-sq NSCLC, respectively). TTC distribution according to the treatment cycle and MP for Non-sq and Sq NCSLC are presented in Figure 1 (A and B), respectively. Figure 1



Conclusion:
Based on current list prices in Israel, the estimated mid-point for total treatment cost is the 5[th] cycle for Non-Sq NSCLC and the 4[th] cycle for Sq NSCLC. Our data may represent a basis for risk sharing discussion between the payers and the manufacturers.

Background:
Cancer treatment practices in the United States are affected by multiple factors to include out-of-pocket patient costs, payer restrictions, and access to care. Facilities in the United States Military Health System offer a unique opportunity to explore treatment practices in a closed system not limited by previously stated factors. We conducted a study to explore the patterns of care and identify unique aspects in the treatment of advanced stage non-small cell lung cancer at a large United States military medical center where patients have no out-of-pocket costs and no payer restrictions.

Methods:
We conducted a retrospective chart review of patients who initiated palliative chemotherapy for NSCLC from 01 July 2011 to 01 July 2014 at San Antonio Military Medical Center. Patient demographics, tumor characteristics, chemotherapy history, and radiology studies were collected.

Results:
A total of 68 patients were included in the review with 54 having stage IIIB or IV disease and the remaining 14 having a metastatic recurrence of earlier stage disease. The median age was 64 with a range from 42 to 91. 41 (60%) were adenocarcinoma, 21 (31%) were squamous, and 6 (9%) were poorly differentiated histology. 57 (84%) patients had an ECOG of 0 or 1 and 50 (74%) had a smoking history. The mean number of lines of chemotherapy was 2.1 with a range of 1 to 6. The average frequency of CT based imaging was every 3 months with contrasted CT scans alone being 2.5 times more frequent than PET CT scans of diagnostic quality. Of the 62 patients without a sensitizing molecular alteration, 55 (89%) were treated with an upfront triplet or doublet platinum based regimen. 59% of patients received at least 2 lines of therapy, 30% received 3 lines, 13% received 4 lines, and 6% received greater than 4 lines of therapy. 14% of patients with negative or unknown EGFR mutation status received erlotinib during later lines of treatment.

Conclusion:
Despite not facing payer restrictions or out-of-pocket costs, patients treated in the United States Military Health System received a similar number of lines of palliative chemotherapy as reported in other retrospective reviews. This study suggests that payer restrictions and out-of-pocket costs may not have a significant impact on the patterns of care in the treatment of advanced non-small cell lung cancer in the United States.

Background:
While there is a growing literature on estimating the tradeoffs between the benefits and risk of cancer care, there is a paucity of literature exploring preferences for the collateral damage associated with long-time side effects. We estimated the treatment preferences of lung cancer survivors and caregivers, and the time equivalents for multiple domains of long-term side effects.

Methods:
Through rigorous engagement of a national advisory board of lung cancer survivors, a discrete-choice experiment (DCE) was developed, pretested and piloted. The DCE was administered to lung cancer survivors and caregivers at a national summit. Respondents completed 13 paired-comparison choice tasks described across six attributes: progression-free survival (PFS), short-term side effects, and physical, emotional, cognitive, and functional long-term side effects. A continuous preference model was estimated using mixed logit. Using PFS as the numeraire, the preference for avoiding side-effects were estimated using their time equivalents by using maximum simulated likelihood.

Results:
Of 114 survey participants, 102 (89.4%) completed all choice tasks - although no difference was identified between those who did not complete the task (p>0.05 for all observed characteristics). All attributes were statistically different form the null (p<0.001). Respondents valued a one-unit decrease in functioning the most, valuing it equivalent to extending PFS by 3.67 months. Changes in physical (2.34) and cognitive (2.29) were valued more than a composite of all short-term side effects (1.83). Heterogeneity analyses (see figure 1) indicated that avoiding long-term side effects could be valued even more highly for some respondents. For example. the 95% confidence interval for time equivalence of functional long-term side effects ranged from 0.62 to 13.31 months.Figure 1



Conclusion:
Despite the limitation of this small, retrospective study, the results indicate that avoiding the long-term side effects could have significant value, especially as many patients experience moderate long-term side effects across multiple domains.

Background:
Drug accessibility and reimbursement remains a major challenge across the globe. The Israeli Ministry of Health (MOH) approves drugs based on previous approval by the FDA and EMA-EU. Compassionate use programs (CPU) represent the use of a compound approved by the FDA/EMA-EU before its approval by local regulatory authorities. CPU provides accelerated access to novel compounds to patients otherwise unable to get the treatment.

Methods:
This is a retrospective analysis of 102 patients treated with nivolumab, osimertinib, or nintedanib within a CPU in a single tertiary Israeli cancer center. Basic patient demographics, different logistic treatment aspects and the time from FDA/EMA-EU approval to reimbursement approval for these compounds in Israel were analyzed.

Results:
We started Nintedanib program by July 2014 when the official MOH approval was 16 months later in Nov 2015. Osimertinib program was started a year before the official approval by MOH and was approved for reimbursement 4 months prior to drug registration. Nivolumab for Non-squamous was started 6 months before approval, while for Squamous the label was approved by MOH 2 months after starting the compassionate program. Reimbursement approval was received 6 months thereafter for nivolumab (Squamous NSCLC). Two out of the three drugs in the program were approved for reimbursement, one of them even before MOH registration. Figure 1



Conclusion:
Compassionate use programs allow access to new cancer drugs prior to their approval by the regulatory authorities, increases physicians' experience with novel compounds and may affect reimbursement approval.

Background:
Background: In Brazil, lung cancer is a public health problem as in the world. The national Incidence in 2016 is estimated in 28.220 new cases[1]. In Rio Grande do Sul, an etimated number of new cases is 4.240[1]. Is well estabilished molecular testing for EGFR, ALK mutations are mandatory to treat metastatic adenocarcinomas to indicate target therapy, or not. Prevalence of EGFR mutations in adenocarcinomas, for example, are estimeted from 25,5% to 30,4%[2,3]. Although many guidelines advocates to use a TKI as first line therapy, in Brazil is difficult becouse nor the drugs, nor the assays are available to public health service, except by legal measures[4], or support from pharmaceutical industry

Methods:
Methods: We made a cross-sectional study from january 2013 to may 2016, collecting data from medical records in our institution, to evaluate our population and how we are handling advanced and metastatic adenocarcinomas in NSCLC patients.

Results:
Results:We found 182 patients with NSCLC (adenocarcinoma), from those 72 was in stage IIIB-IV or with relapsed disease. In 37/72 (51,38%) cases some molecular testing was done (EGFR, ALK); EGFR 26 (36,1%) WT: 9/26 (34,6%), mut: 9/26 (34.6%)(in confirmation), UK (data in confirmation): 8/26 (30,7%); ALK: 10 (13,8%), w-o transloc.: 6/10 (60%); wtransloc: 1/10 (10%); UK (data in confirmation)3/10 (30%). From 72 patients, nine (12,5%) was included in clinical trials; 6/72 (8.33%) recived TKI out of a trial. From these just 2/6 received TKI as first line, and 4/6 as a second line and beyond.

Conclusion:
Conclusions: It will be done after our sample, and assay tests results review.

Background:
Adjuvant chemotherapy is the standard treatment for selected patients with non-small cell lung cancer (NSCLC) following curative surgery. This study evaluated the use of adjuvant chemotherapy for these cases among the general population in Taiwan.

Methods:
A population-based cohort was established by searching the database of the Taiwan Cancer Registry System to identify patients newly diagnosed with NSCLC for the period covering 2005 to 2009. Our target was patients with stage I, II and IIIA NSCLC who had undergone curative surgery. Medication prescription data were retrieved from the National Health Insurance Research Database, Taiwan. Chemotherapy administered within 3 months after the surgery was defined as adjuvant chemotherapy.

Results:
A total of 5789 patients received curative surgery for NSCLC, and the 1277 (22.1%) who had undergone adjuvant chemotherapy were included in this study. Overall, the most common adjuvant chemotherapy regimen was platinum plus gemcitabine (P + G) (25.7%), followed by platinum plus vinorelbine (P + V) (18.4%). For patients with stage II or IIIA disease, P + G remained the most common regimen, respectively (29.0% and 29.0%). However, for patients with stage I disease, the most common regimen was tegafur/uracil (30.7%). Analyzed by the diagnosis year, P + G was the most common adjuvant chemotherapy regimen until overtaken by P + V in 2009.

Conclusion:
Platinum plus gemcitabine regimen was the most commonly used adjuvant chemotherapy regimen in patients with operated stage II and IIIA NSCLC in Taiwan from 2005 to 2009.

Background:
About 28,220 new cases of lung cancer are going to be diagnosed in Brazil in 2016. The epidermal growth factor receptor (EGFR) is a transmembrane protein with tyrosine kinase activity associated with growth, survival, proliferation and differentiation in different human cells. Approximately 25.5% of patients with non-small lung cancer cells (NSCLC) in Brazil present activating mutations in EGFR gene, which confers sensitivity to tyrosine kinase inhibitors (gefitinib and erlotinib).

Methods:
Given the similarity in efficacy observed in RCTs, an economic evaluation under the perspective of the public and private sectors in Brazil was performed using a Markov model. Estimation of direct medical costs was calculated in a group of advanced NSCLC patients with EGFR mutations, undergoing first line treatment with one of the target therapies. A discount rate of 5% was applied on future costs/benefits and the rate of adverse events was extracted from a meta-analysis to estimate its costs.

Results:
According to the model, patients with locally advanced or metastatic NSCLC who have EGFR activating mutations undergoing treatment firstline with gefitinib required less resource versus erlotinib in both perspectives as shown in Table 1, mainly due to the price difference between the drugs (USD 984.22 versus USD 2,033.15 in the public and USD 1,440.31 versus USD 2,439.78 in the private). Table 1. Estimated total costs for first line treatment with gefitinib or erlotinib

	Strategy	Treatment Costs (USD)	Incremental Costs (USD)
Private Sector	Gefitinib	26,637.12	-
	Erlotinib	42,110.00	15,472.88
Public Sector	Gefitinib	16,134.00	-
	Erlotinib	32,045.40	15,911.40

Exchange rate 1 USD = 3.30 BRL (July/2016) Regarding costs related only to the management of adverse events, both strategies were similar in the public perspective (USD 94.15 for gefitinib versus USD 98.21 for erlotinib); however, gefitinib costs were lower than erlotinib (USD 625.27 versus USD 941.32, respectively) in the private sector.

Conclusion:
First line treatment with gefitinib was dominant in comparison with erlotinib for NSCLC patients with EGFR mutation in both public and private sectors in Brazil.

Background:
Despite global improvements in survival non-small cell lung cancer (NSCLC) remains lethal, with 20% five year survival in a limited number of developed nations. Fit, early stage NSCLC patients can be offered curative treatment, using surgery or radical radiotherapy. Geographical variation in surgery usage in England has previously been demonstrated. We aimed to further investigate this variation, incorporating all curative treatments and considering associated survival.

Methods:
Information on 143,886 patients diagnosed with a first NSCLC between April 2009 and December 2013 in England was extracted from the national cancer registration dataset linked to radiotherapy treatment and Hospital Episode Statistics data. In England Clinical Commissioning Groups (CCG) are the statutory bodies responsible for the planning and commissioning of health care services for their local area. We calculated the proportion of patients receiving curative treatment in each CCG, and created quintiles from the resulting distribution. Logistic regression was used to assess the effect of age, sex, stage, comorbidity, performance status and socio-economic deprivation on curative treatment usage. Multivariable Cox regression models were used to analyse survival in relation to curative treatment quintile.

Results:
Overall, 29,580 (20.6%) NSCLC patients received curative treatment: 20,177 (14.0%) NSCLC patients underwent resection and 9,403 (6.5%) received radical radiotherapy. The proportion of patients receiving curative treatments ranged from 11.8% to 31.7% across English CCGs and decreased with advancing age (p < 0.001), increasing stage (p < 0.001) and worsening performance status (p < 0.001). The proportion of patients receiving curative treatment was greater for females compared with males (p < 0.001). The absolute risk of dying within 5 years ranged from 90% in the lowest treatment quintile to 85% in the highest. Increasing curative treatment rates were associated with lower mortality (p < 0.001), with an adjusted HR of 0.93 (95% CI 0.92 to 0.95) in the highest treatment quintile compared with the lowest.

Conclusion:
Despite adjustment for case-mix variables we demonstrated that significant variation in the use of curative treatment for NSCLC persists across CCGs with increasing curative treatment rates associated with lower mortality. There is a need to further explore the factors driving this variation in order to guide changes in care which may deliver improved outcomes.

Background:
To examine guideline concordance across a national sample and to determine the relationship between socioeconomic factors, use of recommended post-operative therapy, and outcomes for patients with pN1 or pN2 non-small cell lung cancer (NSCLC).

Methods:
All margin-negative pT1-3 N1-2 M0 NSCLC treated with lobectomy or pneumonectomy without induction therapy in the National Cancer Data Base (NCDB) between 2006-2011 were included for analysis. Use of guideline-concordant adjuvant therapy, defined as chemotherapy for pN1 disease and chemoradiation therapy for pN2 disease, were examined regarding pathologic, demographic, and socioeconomic factors. Multivariable regression models were developed to estimate predictors of guideline adherence and outcomes. Survival was estimated using the Kaplan-Meier method.

Results:
A total of 9,300 patients were identified. Of these, 7,137 had pN1 disease and 2,163 had pN2 disease. Guideline-concordant adjuvant therapy was utilized in 4,477 (62.7%) pN1 patients and 646 (29.9%) pN2 patients. After multivariable adjustment, patient age (OR 0.59 per decade, 95% confidence interval [CI]: 0.56-0.63), uninsured status (OR 0.52, 95%CI:0.39-0.71), N2 disease (OR 0.21, 95%CI:0.18-0.23), pneumonectomy (OR 0.75, 95%CI:0.65-0.86), longer postoperative length of stay (OR 0.96/day, 95%CI:0.95-0.97) and unplanned readmission (OR 0.76, 95%CI:0.61-0.95) were associated with significantly worse guideline concordance, while higher education levels (OR 1.07 per quartile, 95%CI:1.01-1.14) and increasing T-stage (OR 1.08, 95%CI:1.01-1.16) were associated with significantly higher concordance. Overall, patients treated with guideline-concordant therapy had superior survival (5-year survival: 50.4 vs. 35.3%, p<0.001; Figure).Figure 1



Conclusion:
Socioeconomic factors, including lack of insurance, are associated with disparities in use of adjuvant therapy as recommended by National Comprehensive Cancer Network guidelines. These disparities have significant impact on patient outcomes. Future work should focus on improving access to appropriate adjuvant therapies among the uninsured and socioeconomically disadvantaged.

Background:
Population-based data on Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) gene test status can inform about real-world molecular testing practices and their impact on treatment decisions and outcomes. Yet no efficient methods are available for population-based cancer registries to ascertain molecular testing data of non-squamous non-small cell lung cancer (NS-NSCLC) from electronic pathology (e-path) records. We sought to validate natural language processing (NLP) systems to accurately ascertain EGFR and ALK test use and results in patients with stage IV NS-NSCLC included in the Fred Hutchinson Cancer Research Center’s Cancer Surveillance System (CSS), a part of the U.S. Surveillance, Epidemiology, and End Results (SEER) program.

Methods:
We identified 4,279 e-path reports available in the CSS corresponding to 1,634 patients diagnosed with stage IV NS-NSCLC between 09/1/2011 and 12/31/2013. Using a random sample of 426 (10%) reports, we developed and trained an NLP system to detect EGFR mutation and ALK gene rearrangement test use (test result reported vs. not reported), and test results (positive vs. negative among reported tests). Two oncologists reviewed all e-path reports and resolved discrepancies by consensus to determine the gold-standard classification of test use and results. We report preliminary estimates of the NLP sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EGFR and ALK test use based on a second random sample of 426 reports (testing subsample).

Results:
Of 1,634 patients, mean age was 68 years, 815 (50%) were male, 1424 (87%) were white, and 1,347 (82%) had adenocarcinoma histology. Based on the gold-standard classification, in the training subsample, 126 (30%) and 103 (24%) reports contained information about EGFR and ALK test results, respectively. In the testing subsample, 139 (32%) and 115 (27%) had information about EGFR and ALK test results, respectively. In the testing subsample, the NLP system correctly detected 135 reports that contained EGFR test results and 285 that did not (sensitivity=97%; specificity=99%; PPV=99%; NPV=99%), respectively. The NLP system correctly detected 113 reports that contained ALK test results and 307 that did not (sensitivity=98%; specificity=99%; PPV=97%; NPV=99%), respectively.

Conclusion:
NLP is likely a valid method for capture of EGFR and ALK test use from e-path reports. Ongoing analyses include the NLP validity for ascertainment of test results among reported EGFR and ALK tests in this initial dataset and in a separate validation dataset of 3,427 pathology reports, all of which will be reported subsequently.

Background:
A growing number of clinical guidelines recommend expansion of multidisciplinary care to include supportive/palliative care and survivorship care for oncology patients. Health care delivery systems vary and lung cancer patients may not have the education/awareness or ability to access these recommended services. Our goal was to assess treatment and care planning from the patient and caregiver perspective and to determine whether lung cancer patients are receiving the recommended high-quality care.

Methods:
A Community Needs Assessment survey was distributed to lung cancer patients and caregivers electronically between 11/9/2015 and 2/8/2016. 820 people responded, including 471 patients/survivors and 349 caregivers, 181 of whom were the primary caregiver. The overall completion rate was 72.6%. The survey queried the composition of the patient’s care team, incorporation of values-based discussions in care planning, discussions and plans for palliative care and, where applicable, survivorship care. Demographic information was asked to identify whether patterns of care varied with geographical or socio-economic factors.

Results:
Patient and caregiver reported experiences revealed multiple gaps in the delivery of high-quality patient care. Less than half of patients reported having a conversation about their values and care goals with their treatment team before determining their treatment plan. Less than 30% of patients reported having a psychiatrist/psychologist, social worker, palliative care professional, or nurse navigator as part of their care team in any time period – treatment or survivorship. For palliative care, only 26.9% of active patients had discussed it and 20.13% reported receiving it, despite lung cancer data showing its potential survival benefit. Caregivers reported a higher percentage – roughly 50% reported both palliative care discussions and care receipt. However, for caregiver-reported data, the patients receiving care generally had more advanced cancer and had often not survived. Survivorship care planning was also seen at significantly lower levels than current recommendations. Of those who had completed treatment and survived more than 5 years past diagnosis, only 22% of patients and 15% of caregivers reported having a survivorship care plan.

Conclusion:
Despite recommendations and guidelines for incorporation of palliative care, survivorship care plans, values-based care planning and appropriate psycho-social support into lung cancer treatment, the majority of lung cancer patients and caregivers surveyed reported not receiving these services. Respondents were technology-enabled and generally health-literate indicating that these problems could be more widespread in rural, lower-socioeconomic areas where lung cancer is common. Addressing these problems in health care delivery could positively impact lung cancer patients and their families.

Background:
To date lobectomy patient flows across different geographic units and time periods has not been quantified; little is known about associations between hospital- and patient-level factors and travel choices for surgery and the subsequent outcomes. We explored these issues as well as the robustness of the aforementioned associations with changing geographic health service units.

Methods:
The New York Statewide Planning and Research Cooperative System database (2007-2012) was used to select lung cancer patients who underwent lobectomy by Video-Assisted Thoracic Surgery (VATS) or open thoracotomy techniques. Hierarchical logistic regressions were used to examine factors associated with surgeries occurred within or outside of patients’ geographic units: Health Service Regions (HSRs), Health Referral Regions (HRRs), and Health Service Areas (HSAs), respectively.

Results:
A total of 9,655 lobectomies (43% of which were VATS) from 8 HSRs, 21 HRRs, and 145 HSAs were identified. At the state-level, 17%, 22%, and 56% of the lobectomies occurred outside of patients’ HSRs, HRRs, and HSAs, respectively; the percentages varied spatially but the spatial patterns remained stable from 2007 to 2012. Travel-out patients were more likely to be males or with private insurance, and less likely to be non-Hispanics Blacks, Hispanics, or with Medicaid insurance. Travel-out lobectomies were more likely to be performed by VATS, in urban setting, teaching hospitals, with higher lung surgery volume, and higher numbers of surgeons. In-hospital mortality of travel-out lobectomies was not significantly different from that of the stay-in. These associations were consistent among models using different health service geographic units.

Conclusion:
Lung cancer patients tended to travel farther to be treated with VATS in urban/teaching hospitals with high surgery and surgeon volumes. Other independent determinants of the travel choice included sex, insurance type, and race/ethnicity. Patients’ choices and preferences should be taken into account when planning specialized health care delivery services.Figure 1

Background:
A new episode-based funding model (FM) for ambulatory systemic therapy was implemented in Ontario, Canada in April 2014. The FM bundled reimbursement for components of care, including initial consultation, treatment episodes delivered with adjuvant/curative (AC) or palliative intent and supportive care. Options for evidence-informed AC regimens and their optimal number of treatment cycles and chemotherapy suite visits were informed by the provincial lung Disease Site Group (DSG) based on published literature or group concensus. It was expected that cisplatin-vinorelbine (CISPVINO) would be the most commonly used regimen as CISPVINO was used in the clinical trial conducted in Canada that established CISPVINO as a standard of care and is recommended in Ontario’s adjuvant chemotherapy practice guideline.

Methods:
The utilization of AC was analyzed for 35 systemic treatment facilities in Ontario comparing actual practice (AP) with “best practice” (BP) (cycle number). For this analysis, cases were included if they started a new course of AC after January 1, 2014 and completed the treatment before July 30, 2015.

Results:
The percentage of patients with stage II/IIIa NSCLC receiving AC has been stable at 50-55% for over five years. In this analysis 1,531 cases received some form of AC. 506 cases received chemotherapy with XRT (usually etoposide-cisplatin) and these cases were assumed to be Pancoast tumours or stage IIIa disease on neoadjuvant therapy. The most common regimens prescribed without XRT were cisplatin-vinorelbine (CISPVINO) (331 cases) cisplatin-etoposide (222), carboplatin-etoposide (154) and carboplatin + vinorelbine (74 cases). For all adjuvant chemotherapy excluding XRT (1,025 cases), AP was equal to BP in only 24 % of cases, AP BP in 4%. For CISPVINO, AP=BP was achieved in only 36%, AP< BP in 55% and AP > BP in 9%. For the top 5 hospitals by volume administering AC, BP=AP ranged from 8-45%; AP< BP ranged from 41-73%; AP > BP occurred in 20 cases in 3 facilities.

Conclusion:
This analysis of first-year funding data provided insights on how adjuvant chemotherapy is administered in Ontario. As expected, CISPVINO was the most commonly used AC regimen (32%) when AC was used alone. However, etoposide-cisplatin was also commonly used alone and in combination with XRT and carboplatin was frequently substituted. BP is only achieved in the minority of cases and there is wide institutional variance. Reasons for this variation need to be better understood and opportunities identified to drive efficiency and standardization.

Background:
It is important to investigate the variation of the deaths due to lung cancer in time.The aim of this study is to investigate the variations in the rate of deaths due to lung cancer in Turkey.

Methods:
Data on lung cancer mortality during 2009-2014 years were extracted from the Turkish Statistical Instıtute and Turkey Public Health Agency mortality data based on Internal Classification of Diseases 10(ICD-10)codes C32-C34.For each gender, age group-spesific and standardised rates were calculated by direct standardized method (using the world standard population).These were expressed as rates/100,000 persons.The temporal trend in lung cancer mortality rates were tested for age,gender and methods using Joinpoint Regression Analysis.In joinpoint regression analysis,the best-fitting points where the rate changes significantly (increase or decrease) are chosen.Each joinpoint indicates a statistically significant change in trend,and annual percentage change(APC) is computed for each of trend by means of generalised lineer models assuming a Possion distrubition.

Results:
119.778 deaths due to lung cancer were recorded; 85.50%(n=102409) of the were in men,14.50% (n=17369)were in women. The mean of crude rate of lung cancer mortality is from 2009(23.77 deaths/100.000) to 2014(26.78 deaths/100.000) 26.19 in 100.000, in men 44.00 in women 7.74.The mean of lung cancer age-spesific standardised rates from 2009(49.47 deaths/100.000)to 2014(54.57 deaths/100.000) is 52.50 in 100.000,in men 45.83 and in women 6.62. Lung cancer mortality rates shows a significant increase between 2009-2014.The rates of lung cancer mortality,between 2009-2014 with 4.2% (%95 Confidence Interval: 3.2 to 5.3)showed an important increase annually(p<0.001).During working period, throughout men the variation 4.1%(2.8 to 5.5)in the lung cancer mortality rates were significant(p<0.001).Similar situation was in women with 5.0%(3.7 to 6.4)(p<0.001)The deaths due to lung cancer in young age(under 44 years )in women(5.27%)is more than men(2.59%)(p<0.001). The decrease of -5.4%(-1.5 to 5.3)in deaths due to lung cancer seen in young men(under 45 years) within years was not significant(p=0.20). Similarly in women with same age the variation 3.1%(-2.7 to 9.3 was not significant(p=0.30). The variation in men between the ages45-64 deaths due to lung cancer within years 1.5%(-0.3 to 3.4)was not significant(p=0.10).Unlike in women in this age group with 3.8% increase(2.2-5.5)showed significance(p<0.001). The increase in deaths due to lung cancer seen in men in 65 years of age and over 4.4%(3.6-5.2)was significant(p<0.001).With the same result in women 2.6%increase(1.1-4.1)was seen(p<0.001).

Conclusion:
Even though deaths due to lung cancer show non-significant decrease in male, shows significantly increase above 65 years of age. Increase in lung cancer in young women is remarkable.

Background:
In the last decade Europe has faced a sharp slowdown in Clinical Research (CR) mainly due to European Directive 2001/20/CE application.Consequently the European Commission enacted the EU Regulation 536/2014 (ER) that is expected to become effective only in 2018, due to delays in the portal development. To investigate the ER perception and knowledge of the Italian professionals, two online surveys, addressed to Clinical Research Coordinators (CRCs) and Clinical Investigators (CIs), were conducted.

Methods:
Two anonymous web-based surveys, both consisting of 17 questions, have been used.

Results:
The 62.5% and 58.9% of the contacted CIs and CRCs respectively answered to the survey: 12% of the CIs have a fully knowledge of the incoming ER while many are only partially (64%) or not (24%) informed. 80.4% of CRCs demonstrate a complete knowledge and are already trained. Amongst the evaluated topics, the need of a Reporting Member State in the first stage of the evaluation process is considered as positive by 74% of the CIs and almost all (90%) believe that this procedure will reduce the approval time. With regards to newly imposed transparency standards, 86% of the CIs would welcome the publication of trial results, while 14% believes that this obligation should only apply to profit trials. Overall 70% of CIs state that staff site’s facilities already met all of the ER imposed qualification. The 50% of CIs foresee that the ER will promote independent CR while 42% supposes that it will essentially affect the profit trials. Even though 71.4% of CRCs do not have a definite opinion on ER,85.7% is convinced that it will have a direct impact on their job.

Conclusion:
The ER is a turning point for European CR: it is designed to ensure faster procedures, with positive effects both on timing and overall costs and it will require a rigorous methodology and an increased quality. The surveys highlighted different opinions among CIs and CRCs on Italian ability to rise to this challenge: while CIs believe that the centers already met the imposed requirements with only an initial period of transition, CRCs are less optimistic and report fails of their management to engage plans to be ready to the ECTR adoption. This process will involve big efforts and resources, but the payback is the opportunity to be on board of innovative treatments for the Italian patients.

Background:
The role of multidisciplinary teams (MDTs) is central to lung cancer care in Australia with support at policy level and with the development of a nation-wide lung cancer MDT directory from Lung Foundation Australia. In parallel, the importance of accessible, clinically relevant information from routine data collection in lung cancer (as well as other tumour streams) is receiving increased recognition. MDT meetings increasingly act as central hubs for the co-ordination of lung cancer care and therefore have the opportunity to focus on quality assurance as well as analyses of patterns of care and identification and targeting of evidence-practice gaps. MDT meetings can act as central sources of data collection and analysis and as such a standardized approach to lung cancer MDT data collection in Australia is warranted. This study will present the results of a modified Delphi study, surveying Australian lung cancer clinicians, aiming to finalize an ideal clinical dataset for collection through lung cancer multidisciplinary meetings.

Methods:
A 17-item survey has been circulated to a broad, representative sample of lung cancer clinicians, medical and allied health, in Australia. Clinicians were identified and contacted either as (1) part of a purposive sample or (2) through MDT lead clinicians identified through convenience or through the Lung Foundation Australia Lung Cancer MDT registry. Results of an initial survey will be analyzed and a second-round survey will be circulated to an expert panel drawn from the first-round participants prior to finalization of the dataset.

Results:
The first round of the survey is reaching completion at the time of abstract submission. A total of 98 responses have been received across the two sampling strategies in the 4 weeks since surveys were distributed. Initial data analysis showed a predominance of pulmonary physicians, attendance at MDT weekly more than fortnightly, support for inclusion of most of the variables presented in the survey and a leaning towards MDT presentation of complex/multimodality therapy and stage IIIA cases rather than all cases of lung cancer.

Conclusion:
The findings of the study will support the development of a standard dataset for collection at lung cancer MDT meetings. This dataset will be utilized in future planned studies across multiple sites for targeted data intervention and feedback strategies and analysis of effect on lung cancer outcomes.

Background:
Measurement of value is increasingly important in cancer care, specially in lower-income countries. Grupo COI is a Brazilian private cancer care institution, member of the ICHOM (International Consortium for Health Outcomes Measurement) working group for lung cancer standard set definition. We report here feasibility and results for the first year of implementation.

Methods:
Lung cancer (LC) patients inclusion started on June/2015. Data were prospectively obtained from medical charts and patients interviews. All patients signed an informed consent (IC) and were only included if they would receive entire treatment at our center. ICHOM standard set outcomes included survival, complications during or within six months of treatment, baseline demographic, clinical, and tumor information and patient-reported quality of life evaluation (EORTC QLQ-C30 and QLQ-LC13) .

Results:
A total of 392 LC patients were admitted at COI, but only 120 patients (30.6%) met inclusion criteria. Main reasons for exclusion were partial cycle of care at COI (64.9%) and any treatment started before IC signature (11.3%). Median follow up was 7.9 months and baseline clinical data are presented in Table 1. Patient reported outcomes (PROs) were obtained from paper and phone calls. PROs assessment deviations were reported in 49 patients (38.5%) and reasons for them were application date error (63.2%) and patient or family refusal (36.7%). Cost data are being registered for future analysis. Table 1. Baseline Clinical and Demographic Characteristics

Median age - years (variation)	68 (36 – 91)
Gender
Male	57 (47%)
Female	63 (52%)
Educational Level
Primary	21 (17%)
Secondary	36 (30%)
Tertiary	63 (52%)
Performance status
0-1	101 (84%)
2	6 (5%)
3-4	0
Non specified	13 (10%)
Histology
Adenocarcinoma	66 (55%)
Squamous-cell carcinoma	29 (24%)
Small cell carcinoma	12 (10%)
Others	13 (10%)
Stage
I-II	21 (17%)
III	29 (24%)
IV	70 (58%)

Conclusion:
Applying an international value-based outcome standard set at a Brazilian institution is feasible. Based on these first data, improvements on PROs assessment methodology are being considered, like self-report electronic forms. Some inclusion criteria should also be revised to avoid this large number of patients exclusion, in order to reproduce a real-world scenario.

Background:
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of primary lung cancers, the majority of patients presenting with advanced disease at diagnosis. In the last decades there has been significant progress in the understanding of lung cancer molecular biology, which has influenced on treatment choices. The prevalence of EGFR mutations in non-squamous NSCLC population range from 15% to 40%, depending on the population that has been assessed. Brazilian people are marked by high miscegenation, and there is lack of data about EGFR mutations in this population. This study intends to report the prevalence of such mutations in Brazil.

Methods:
We performed an observational retrospective study of 324 patients treated for advanced NSCLC from january 2014 to may 2016 from two institutions. 80 (24,7%) patients had squamous NSCLC and were not tested for EGFR mutations. The others 244 non-squamous NSCLC patients had their medical record reviewed and information regards the EGFR mutation status were obtained. Patients were stratified by sex, age, histological subtype, and type of mutation.

Results:
51 cases (22% of adenocarcinomas) with EGFR mutations were identified. The most frequent genetic alteration detected was exon 19 deletion (64,7%), followed by L858R mutation (19,6%). 34 EGFR mutated patients (66,7%) were women, as man accounted for 60% of all the NSCLC cases.

Conclusion:
Our findings support previous studies that showed an EGFR mutation rate about 20% in non-squamous NSCLC and its higher prevalence in women population. This research is also important in terms of public health, since knowing how many cases of mutated NSCLC are expected in this region, better we can manage the costs of these patients treatments.

Background:
The recent genomics revolution has provided unprecedented insights into the molecular complexity of cancer cells. Even within the same individual, tumor cells adapt to their environment, evade treatment attempts, and develop resistance against initially efficacious treatments. NSCLC has been shown to be among the most complex cancer types. Multiple approaches, in combination, hold promise to gain ground against this hard-to-treat disease. At the same time, successful preventive efforts can substantially reduce disease burden by decreasing the incidence of the disease. Depending on an individual’s preferences, treatment goals may vary from emphasis of quality of life to seeking a lasting cure even at the cost of substantial side effects. This complex picture of etiology, treatment strategies, and patient preferences must be reflected in any assessment of progress against the disease.

Methods:
We previously introduced the PACE Continuous Innovation Indicators™ (PACE CII) to measure progress against 12 different solid tumor types (https://pacenetworkusa.com/continuousinnovation). In the present work, we expanded the functionality of the tool to include an interactive user interface based on the Shiny (R online) platform that allows for custom-weighted analyses. We used this tool to compare progress against NSCLC with other tumor types when different weights are assigned to different treatment contexts and goals.

Results:
When assigning the largest weights to advanced and/or metastatic disease, NSCLC has seen the most progress (i.e. E-Score increase) over the past 30 years among the 12 common tumor types included in the tool. When focusing on progress against early stage disease and in the adjuvant context, however, NSCLC loses its top position to breast cancer. In both analyses, evidence for treatments that increase survival begins to accumulate in the 1990s and accelerates in the early 2000s, partly driven by the advent of targeted treatments.

Conclusion:
The global fight against cancer is a very substantial societal investment, and being able to track progress in specific domains will likely be critical for focusing this endeavor. To account for the complexity of the disease, progress cannot be summarized by a single metric. We here show how the PACE CII can help obtain a multi-faceted, complex picture of progress across the entire spectrum of tumor complexity and based on varying patient values. We encourage the field to use this public database to conduct additional analyses based on individual interests and preferences.

Abstract not provided

Abstract not provided

Abstract:
Advances in modern technologies allows for an increasing opportunities in surgical and medical education. The main advantages for e-learning process are: accessibility and flexibility. A range of platforms offers educational programs accessible at work or home with total temporal and spatial freedom. Trainees are allowed to access their learning environment at a convenient time and relevant to their own training needs. Several techniques are available: web-based data, interactive online modules, and virtual reality. This is especially true within surgical training where the development of new techniques constantly evolves. The rapid and constant evolution in oncology knowledge’s makes it relevant for e-leaning process. E learning allows trainees to apply and be assessed on the new information in a safe setting. In addition, all contents can be discussed and debated around the medical world without any limits. The level of trainees recall can be significantly increased by e-learning techniques because it stimulates multi-sensory experiences. E learning offers also large possibilities for decision making based on available information and interactive decision-making process. Surgical e-learning programs include the development of knowledge, technical skills, non-technical skills and decision-making process. The content of all the e-learning modules should be relevant; best available, up to date and critically appraised evidence should supports the information contained within the modules. E-learning surgical programs should be based on an understanding of educational principles, peer review resources associated to creativity. It could be highly interactive. Immersive questions and answers for clinical setting permit to trainee to progress through scenarios and makes the relevant decisions and choices. Trainees have to evolve with their decisions and receive feedback as to the choices they have made. These interactive models can be created with text on the page or with simulators. E-learning modules should be used as a complementary tool to traditional learning methods. Authors will present their e-learning thoracic platform created at September 2013 : “Tenon Thoracic Institute“ (www.tenon-thoracic-institute).This e-leaning thoracic platform develops several e-learning tools: live from OR with interactive discussion with faculty, round table with exerts, didactic session for young trainees. All the aspects around thoracic pathology are treated: oncology, surgery, anaesthesiology, radiology, etc. Authors will discuss the relevance of such a platform, the lack of its content and future e-leaning projects.

Abstract:
The following is in part the STS, TSDA and AATS combined response to ACGME (collated and written up by Dr. Ara Vaporciyan) regarding the effect of Duty hour regulations on resident education in Thoracic Surgery in North America. A greater reliance on midlevel providers and physician extenders. This has impacted the profession in terms of additional cost from their much higher salaries, which are anywhere from 50% to 100% higher, but also a subtle but steady transfer of bedside teaching previously focused on the trainee to bedside teaching focused on the mid-level provider. Limited exposure to our field. Our profession still fills the bulk of its training position from general surgery graduates. Duty hour restrictions have contracted the ability of those programs to provide elective rotations in thoracic and cardiac. Limited exposure translates into limited interest and diminished applications. Quality of Surgical and postoperative teaching. This is where we have felt the greatest impact. We, like all surgical professions, have developed an increasing variety of procedures necessitating expansion of our case log requirements. This puts pressure on trainees to participate in every available case. Appropriate cases are harder to find due to increasing case complexity and outcome reporting. Therefore, the inability to scrub on just one or two of these cases can be significant. While some large surgery programs have implemented float pools to ensure that all cases provide someone a learning experience most CT training programs are small and cannot implement that solution Even more difficult to overcome is when a trainee misses a rare postoperative event. As a high acuity specialty our patients will frequently develop rapid changes in their condition which, if not recognized, can quickly become catastrophic. Most occur in the immediate postoperative period at night. The use of mid-level providers and other services to cover call in an effort to preserve a trainee’s ability to do cases the next day prevents them from taking part in the bedside assessment and management of these rare events. One solution is to lengthen training to allow more opportunities but there is concurrent pressure to reduce what is already one of the longest training paradigms (up to 9 years for congenital surgeons without considering any time for research). Alternatively simulation has been used but these are expensive and are not easily implemented at all programs.. Finally, issues of patient safety and outcomes. While there is no clear study demonstrating documented impact on patient safety there are many surveys of resident and faculty perceptions of patient safety. The majority of these, especially in surgery, have shown that the perception is that safety is compromised. The increased number of handoffs, especially of high acuity cases, is frequently the target of that perception. The subtle aspects of the intraoperative findings cannot always be accurately communicated in a handoff. While patient safety data is not conclusive there is data on worse outcomes in spinal and meningioma surgery post implementation of duty hour regulations. These data may serve to corroborate the perceived concerns.

Abstract:
WCLC Extended Abstract: The Role of Scientific Organizations Paul A. Bunn, Jr, MD, FASCO The goal of scientific organizations is to facilitate progress in a specific area through promotion of research, training and education. In some instances the scientific area may be a single discipline such as medical, surgical or radiation oncology, pathology, radiology and so on. In some instances the scientific area may be a single geographic region such as Europe, North America or Asia. Examples of such organizations would be the European Respiratory Society (ERS), the American College of Radiology, the College of American Pathology (CAP) and many, many others. In some instances the organization might focus its efforts on training and research grants and in other instances the organization might focus on education of the public and in public programs such as prevention. In some instances the organization may conduct research or may solely sponsor research to be done by others. Some scientific organization chose to develop guidelines for clinical care. All of these efforts are important and different organizations focus on different aspects of a problem. In this presentation I will focus my attention on The International Association for the Study of Lung Cancer (IASLC) since it is the sponsor of the World Conferences on Lung Cancer and since is programs are dedicated to reducing the world wide burden of thoracic cancers. Lung Cancer is the leading cause of cancer death worldwide and the most preventable. When the IASLC was organized in 1974 it was recognized not only that lung cancer was the leading cancer killer but also that it would take an international and multidisciplinary effort to make progress. The very international and multidisciplinary nature of the IASLC are what set it apart from other organizations. Many of the unique contributions of the IALSC rely on these differentiating aspects. For example, the IASLC has contributed all the cases and evaluation of the world wide lung cancer, mesothelioma and thymoma TNM staging classifications. The IASLC Pathology committee has formulated all of the changes to the pathologic classification of thoracic cancers. The IASLC has worked with other organizations such as the College of American pathology and Association of Molecular Pathology to develop guidelines on molecular characterization of lung cancer. To enhance worldwide collaboration and education the IASLC began the World Conferences on Lung Cancer and rotated these conferences to different regions around the world. Originally, these conferences were held every 3 years as progress was slow but as research and research advances have quickened, the WCLCs are ow held annually. In addition the IASLC sponsors regional meetings on a routine basis including the European Lung Cancer Conference (ELCC), the Latin America Lung Cancer Conference (LALCA), the Asia Pacific Lung cancer conference and the Chicago Multidisciplinary Lung Cancer conference. The IASLC also sponsors workshops on various timely topics such as a conference on Small cell lung cancer held in 2015. To support its educational and research missions the IASLC publishes a scientific journal entitled Journal of Thoracic Oncology which has continually increased its circulation and impact factor. More recently, the IALSC has reinstituted a weekly newsletter and has published monographs on time issues such as ALK and PD-L1 testing. The IASLC has sponsored research grants especially for junior faculty and fellows to support and nurture their research careers. The IASLC has also sponsored travel fellowship awards for junior investigators and for young faculty from developing countries. The IASLC had worked with advocacy groups from around the world to provide information and support to these groups and to individuals and families afflicted by lung cancer. These efforts have led to a sharing of efforts and to publications directed to patients and their families. The IASLC’s tobacco committee has worked tirelessly to combat the worldwide tobacco epidemic. References: Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FRThe International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016.. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23. Review Bunn PA Jr, Minna JD, Augustyn A, et al. Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?J Thorac Oncol. 2016 Apr;11(4):453-74. doi: 10.1016/j.jtho.2016.01.012. Epub 2016 Jan 30. Review Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.J Thorac Oncol. 2016 Jan;11(1):39-51. doi: 10.1016/j.jtho.2015.09.009 Hirsch FR.International Association for the Study of Lung Cancer (IASLC): celebrating 40 years with scientific and educational achievements!J Thorac Oncol. 2014 Oct;9(10):1424-5. doi: 10.1097/JTO.0000000000000340. Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E, Van Schil P; Staging and Prognostic Factors Committee; Advisory Boards. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S88-96. doi: 10.1097/JTO.0000000000000293. Tsao MS, Travis WD, Brambilla E, Nicholson AG, Noguchi M, Hirsch FR; IASLC Pathology Committee. Forty years of the international association for study of lung cancer pathology committee..J Thorac Oncol. 2014 Dec;9(12):1740-9. doi: 10.1097/JTO.0000000000000356. Leighl NB, Rekhtman N, Biermann WA, Huang J, Mino-Kenudson M, Ra malingam SS, West H, Whitlock S, Somerfield MR. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study oflung cancer/association for molecular pathology guideline. J Clin Oncol. 2014 Nov 10;32(32):3673-9. doi: 10.1200/JCO.2014.57.3055. Epub 2014 Oct 13 Hung JJ, Yeh YC, Jeng WJ, Wu KJ, Huang BS, Wu YC, Chou TY, Hsu WH. Predictive value of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in tumor recurrence and patient survival. J Clin Oncol. 2014 Aug 1;32(22):2357-64. doi: 10.1200/JCO.2013.50.1049. Epub 2014 May 5 Detterbeck FC, Asamura H, Crowley J, Falkson C, Giaccone G, Giroux D, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson A, Okumura M, Ruffini E, van Schil P, Stratton K; Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain The IASLC/ITMIG thymic malignancies staging project: development of a stage classification for thymic malignancies. J Thorac Oncol. 2013 Dec;8(12):1467-73. doi: 10.1097/JTO.000000000000001

Abstract:
The role of Patient Advocacy organizations in the oncology health care delivery ecosystem is ever evolving and has moved well beyond its original role of solely advocating for services, research, care and understanding. The current field of patient advocacy has its roots in the patient rights movement of the 1970’s with groups like The National Welfare Rights Organization being instrumental in getting a patient bill of rights accepted by the Joint Commission on Accreditation of Healthcare Organizations in 1972[1]. The transformation was further accelerated in 1991 with the formation of the FDA Patient Representative Program and has continued to expand over time with patient advocates now being involved in the entire care continuum. In this presentation I will focus my attention on examples of the ever evolving and expanding role of patient advocacy highlighted by projects developed and led by "partner" foundations the Bonnie J. Addario Lung Cancer Foundation (ALCF) and the Addario Lung Cancer Medical Institute (ALCMI). Addressing Disparities in Care The disparities in lung cancer treatment and outcomes among underserved populations are well documented[2]. Further, 80% of cancer patients are treated in the community hospital setting yet may not receive the same level of care as those treated at leading academic centers. The ALCF Community Hospital Centers of Excellence (COE) program addresses this unmet need. The COE program is a patient-centric model for lung cancer that establishes a standard of care for community hospitals which often treat underserved patient populations. The COE program, which currently includes 13 hospitals in regions of high unmet need, aims to improve the standard of care, patient experience and patient outcome by offering patients and caregivers the same type of multi-disciplinary and comprehensive care provided at leading academic centers. ALCF also provides lung cancer education and services to patients, caregivers and the community. The COE program tracks patient process data longitudinally for multiple quality-of-care metrics, including disease stage at diagnosis; molecular testing; tumor board review; time from diagnosis to treatment; treatment type; and clinical trial participation. Site data will also be monitored to provide a contextual picture of the program including total patients seen, demographics, insurance mix, rates and outcomes of molecular testing among other metrics. Data is analyzed across the COE community and against comparator groups to demonstrate impact of the COE program[3]. Accelerating Clinical Trial Accrual The U.S. National Institutes of Health database currently lists over 45,000 cancer-related clinical trials worldwide[4]. Unfortunately, more than 20% of these trials will never complete, for reasons unrelated to the effectiveness of the intervention that’s being tested. The most common reason for 20% of all clinical trials never finishing is poor patient accrual. One of the most common reasons for low accrual is procedural inefficiencies such as complexities in enrolling in the trial itself and the informed consent process. In 2014, ALCMI launched a prospective study to characterize somatic and germline genomics of adolescents and young adult (AYA) patients[5]. It is estimated that less than 2% of those newly diagnosed with lung cancer globally are AYA, thus presenting a striking recruitment challenge. To address this challenge, ALCMI's study workflow included building a dedicated website[3] enabling remote screening and e-consenting so patients could participate from their homes anywhere in the world while, in parallel, ALCF employed social media to educate patients on the importance of comprehensive genomic profiling and increasing awareness of the study via grass-roots patient blogging. Together, ALCMI and ALCF bring "research to the patient". Accrual opened July 23, 2014 and in the first 5 weeks of the study, 37 subjects consented. Of the 37 initially consented, 35 enrolled via the remote web-portal. As of June 15 2016, 104 subjects are enrolled (128 consented) in the study from 10 countries following a social media campaign. Of the 104 subjects enrolled to date, 49% entered the study via the remote study portal with the balance recruited locally by participating ALCMI study sites Conclusion As briefly outlined above, patient advocacy organizations have moved well beyond their original patient supportive role and have become key players in the oncology healthcare delivery and clinical research ecosystems. As the healthcare system continues to evolve and become more complex so will the role of patient advocacy organizations. To address these challenges, there will be even greater need for innovation, sharing of data and resources, increased infrastructure and mission sophistication, the need to avoid overlap and duplication, and a laser focus on providing meaningful improvement in the availability, transparency and affordability of healthcare. References: 1. Ruth R. Faden, Tom L. Beauchamp, A History and Theory of Informed Consent, (Oxford University Press, 1986), 93 2. http://www.gotoper.com/publications/ajho/2015/2015feb/lung-cancer-disparities-in-the-era-of-personalized-medicine 3. Leah Fine[1], Guneet Walia[1], Raymond U. Osarogiagbon[2]; [1]Addario Lung Cancer Foundation, San Carlos/United States of America, [2]Baptist Cancer Center, Memphis, TN/United States of America. The ALCF Centers of Excellence Model Delivers a Standard of Care to the Community Similar to Academic and Research Centers. World Conference on Lung Cancer, Abstract 6334, December 2016 4. https://clinicaltrials.gov. 5. Barbara J. Gitlitz, Alicia Sable-Hunt, Steven W. Young, Andreas Kogelnik, Danielle Hicks, Deborah Morosini, Tiziana Vavala, Marisa Bittoni, S. Lani Park, Silvia Novello, Geoffrey R. Oxnard, Bonnie Addario (in press). Employing Remote Web Consenting and Social Media to Facilitate Enrollment to an International Trial on Young Lung Cancer. World Conference on Lung Cancer, Abstract 4180, December 2016 6. https://www.openmednet.org/site/alcmi-goyl

Abstract:
The role of medical journals David Collingridge Editor-in-Chief, The Lancet Oncology and Publishing Director, The Lancet Specialty Journals, 125 London Wall, London EC2Y 5AS, United Kingdom; Clinical Associate Professor of Radiation Medicine, Hofstra/Northwell Health, Lake Success, NY, USA. For many years the traditional peer-reviewed medical journal was seen to be the only reliable place to obtain the latest advances in science and medicine. But, with the advent of online depositiories, information services and feeds, news services, preprint servers, data-sharing, and open access, to name just a few recent innovations, the role of the medical journal is changing. Whilst it is true to say that for many physicians, certain journals are still seen as an authorative voice and a vital source of validated data to inform practice, this isn’t the case for all—indeed, any reasonably reputable source of information, especially if easily available online, is increasingly considered to be a valid fount of medical evidence. So what is the role of the medical journal in the online era? How do medical journals remain relevent, continue to offer a valuable resource of practice-defining information, and play a important and collaborative role with their respective communities? How do medical journals not succumb to the fate of the newspaper or music industries, in which the online revolution has caused considerable upheaval—which many might argue has not resulted in a postive evolutionary change for the betterment of all stakeholders? The central tenet for any medical journal is publication of trustworthy data that have been thoroughly reviewed and challenged prior to publication to ensure the interpretation is accuate, honest, and will not cause harm if used in the real world. Moreover, a good medical journal should be much more than this, and must show leadership; take risks; distil the most important information to a time-poor readership; provide innovative ways of linking disparate, but inter-related, strands of information to a readership that no longer reads cover-to-cover; and encourage scientific debate rather than simply reporting it. A good contemporary medical journal therefore needs to be more than just a mirror reflecting the lastest research or thinking without contest: it must inform and drive research and clinical practice forwards. There are multiple ways in which this can be achieved. First, a journal must offer a impartial platform for presentation of data and discussion of ideas without prejudice, and ensure studies are reported rigourously, transparently, and honestly. The activities of an unconflicted editorial team and well-qualified peer reviewers are vital in this regard, as is the application of reporting standards to ensure all data and analyses are captured accurately. Second, journals have a responsibility to ensure the ethical integrity of everything they publish. Journals should be active members of independent ethics organisations and uphold the highest standards. If any suspicion of misconduct occurs surrounding a published article, reputable journals should always investgiate such allegations, which often relate to issues such as: research conduct; reproducibility of data; unethical behaviour in the laboratory or institution; plagarism; withholding of pertinent data and misreporting; conflicts of interests; authorship disputes; or compliance with prevailing governance structures. Academic institutions take these issues very seriously because of the ramifications for their own integity, and thus journals and instititions must work together to root-out any misconduct and ensure the medical literature is trustworthy and organisations practice science and medicine of the highest standards. Third, journals can help further the practice of good science by taking a leadership role in forward-focused programmes. Recent examples include the team science programmes in the UK and USA, and the REWARD initiative. The UK Academy of Medical Sciences Team Science project has been focused on how biomedical researchers can be encouraged, supported, and rewarded for participating in team-based collaborations—editors and publishers are clear stakeholders in this debate; whilst the REWARD (REduce research Waste And Reward Diligence) campaign encourages everyone involved in biomedical research to critically examine the way they work to reduce waste and maximise efficiency via five guiding principles: setting the right research priorities; using robust research design, conduct, and analysis; making sure regulation and management are proportionate to risks; ensuring all information on research methods and findings are accessible; and guaranteeing reports of research are complete and usable. Finally, a fifth role for medical journals is to take an dynamic part in advocating change, leading the direction of future research, and actively participating in health policy reform and in initiatives to promote universal access to medicine. The Lancet Oncology’s advocacy programme, for example, maps out the inequalities and inequities in health systems worldwide, and highlights deficiencies in all aspects of cancer care, health policy, structural organisation, and leadership. The programme offers a impartial platform that brings together thought-leaders from across different disciplines and organisations to offer solutions to those barriers that hinder provision of high quality cancer control, irrespective of socioeconomic status or country of residence. The journal achieves this via specific, dedicated undertakings including Commissions, series of inter-related papers on specific themes, targeted articles, conferences, and events. The medical journal in the 21[st] century must evolve from being a simple record of research to an engaged stakeholder advocating and leading change in the practice of medicine. Journals should aim to be platforms that bring together communities and thought-leaders rather than disenfranchise groups in to silos. The world has never been as interconnected as it is today, and it is only by working together with a clear vision that journals, hand-in-hand with the communities they serve, will achieve the progress needed to promote the best research and health policies to improve healthcare for all.

Abstract:
Lung Cancer – What media can/should do Oncology today is one of the main topics of health/medicine media coverage. With the advent of targeted and immunotherapies there’s been a shift towards presenting the rapid advances in this field. But contrary to topics like skin cancer, breast and colorectal cancer lung cancer has stayed in the shadows of reporting until now. It has all been anti tobacco campaigns often regarding smokers immoral, stigmatizing the patients. Late diagnosis and advanced disease plus bad prognosis have not made lung carcinoma a hot topic – and patient advocacy groups, often key players in getting topics into the broad public, are rare. What we have to do (besides non smoking campaigns): Produce valid information on the developing field of early diagnosis (in risk groups). Inform about advancing science and medical procedures to overcome this old nihilistic view of lung cancer as something too poor and bad to speak and write about.

Abstract not provided

Abstract:
As technology has advanced, modern radiotherapy (RT) techniques, such as conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT), and proton therapy (PT), have become available. In this session, the advantages of these techniques in the treatment of early-stage and locally-advanced lung cancer will be presented, along with their uncertainties. Conformal RT uses CT scans to create 3-dimensional images of the tumor and normal tissues, which leads to more accurate treatment planning. It also uses multiple radiation beams from various angles to concentrate the radiation dose to the tumor while reducing the dose to normal tissues. Furthermore, conformal RT improves tumor control and reduces toxicity compared to 2-dimensional RT (1). IMRT is a sophisticated form of CRT, which enables us to more exactly concentrate and shape the dose distribution to the tumor and spare normal tissues. It can also partially intensify doses to individual areas deemed to be more aggressive or radioresistant. PT uses charged particles, which have a unique physical characteristic called the Bragg peak. The Bragg peak describes a certain tissue depth at which the protons stop just after transferring most of their energy. This feature is particularly convenient for tumors located close to critical normal tissues. PT is commonly adopted for pediatric, central nervous system, and intraocular malignancies. Stereotactic body radiation therapy (SBRT), also called stereotactic ablative radiation therapy (SABR), is characterized by accurate target definition, precise tumor positioning, steep dose gradients outside targets, and very high dose per fraction. SBRT can be delivered using either CRT or IMRT. In the treatment of peripheral early-stage lung cancer, SBRT is widely adopted as a standard treatment and is considered better than conventional fractionated RT. PT can also be used in this setting, despite similar outcomes as SBRT (2); however, a recent systematic review of cost-effectiveness analyses did not support the use of PT (3). To improve outcomes in locally-advanced lung cancer, IMRT and PT have been actively investigated. Several in silico studies have suggested the superiority of IMRT over CRT, and PT over IMRT, but this remains to be demonstrated clinically. Subgroup analyses of RTOG 0617, which compared a high dose (74 Gy) vs. a standard dose (60 Gy) and allowed both CRT and IMRT, showed similar efficacy, less radiation pneumonitis, and better compliance of consolidative chemotherapy favoring IMRT over CRT, despite there being more advanced cases in the IMRT group (4). The study authors generated a hypothesis that dose intensification by IMRT may result in better efficacy with less toxicity. However, we could not determine the true difference between IMRT and CRT among patients who received the standard dose, which is our current practice, because their analysis included both high- and standard-dose arms; the differences might be more prominent in the high-dose arm. These investigators also suggested that increasing the radiation dose to the heart may worsen survival, so dose constraints to the heart became stricter thereafter. Results of a Bayesian phase II randomized trial of IMRT vs. PT were reported at the ASCO Annual Meeting earlier this year (5). The primary endpoint was incidence and time to protocol failure, defined as Grade 3 or higher pneumonitis or local failure. The observed local failure rates at 12 months were similar (13% vs. 12%). The investigators assumed Grade 3 or higher pneumonitis of 15% in the IMRT arm and 5% in the PT arm; however, they observed 6.5% in the IMRT arm, which was lower than the assumed probability, and 10.5% in the PT arm, higher than expected. Because this was a phase II trial with some limitations, firm conclusions could not be drawn. However, PT failed to suggest a clinical benefit over IMRT. A meta-analysis of the phase III trials conducted by the Radiation Therapy Oncology Group between 1968 and 2002 showed that new treatments were demonstrated to be better than existing ones in only 6 of 59 comparisons. In addition, overall survival of all of the accrued patients did not differ between groups, while the odds ratio of 1.76 for treatment-related death was significantly higher for the new treatments (6). These results clearly showed that “New is not always better.” We need to identify the subpopulations for whom new techniques are more effective and to demonstrate these have true value with scientifically strong evidence, instead of just believing in their efficacy, complaining about the challenges associated with evaluating them, or advertising them directly to patients. Figure 1 References 1. Chen AB, Neville BA, Sher DJ, et al. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol 2011;29:2305-2311 2. Grutters JP, Kessels AG, Pijls-Johannesma M, et al. Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: a meta-analysis. Radiother Oncol 2010;95:32-40 3. Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-effectiveness studies of proton radiotherapy. Cancer 2016;122:1483-1501 4. Chun SG, Hu C, Choy H, et al. Outcomes of intensity modulated and 3D-conformal radiotherapy for stage III non-small cell lung cancer in NRG Oncology/RTOG 0617. J Thorac Oncol 2015;10:S213 5. Liao ZX, Lee JJ, Komaki R, et al. Bayesian randomized trial comparing intensity modulated radiation therapy versus passively scattered proton therapy for locally advanced non-small cell lung cancer. J Clin Oncol 2016;34 (suppl; abstr 8500) 6. Soares HP, Kumar A, Daniels S, et al. Evaluation of new treatments in radiation oncology: are they better than standard treatments? JAMA 2005;293:970-978

Abstract:
Lung cancer is the most frequent cancer and the leading cause of cancer mortality. Lung cancer treatment results in terms of patients' long-term survival and cure are far from ideal. Radiotherapy as one of the lung cancer standard treatment modalities can be applied with curative or palliative intent. Radiotherapy treatment intent depends on tumor extent (disease stage), tumor location, patient’s performance status and comorbidities, availability of modern radiotherapy treatment machines and their technical and software capabilities (1-4). Radiotherapy with curative intent is indicated as an alternative to surgical treatment in patients having the early stage disease (generally stages I and II) or a locally more advanced disease (stage III). In early stage disease patients, which are the group with the best prognosis, radiotherapy can be applied as, for example, the sole treatment modality in the form of hypofractioned stereotactic ablative radiotherapy (SABR) for patients with lymph node-negative peripheral non-small cell lung cancer (NSCLC). For patients having inoperable locally advanced lung cancer (stage III) the five-year overall survival rate is at around 15-20%. Therefore, the two remaining standard treatment modalities, chemotherapy and radiotherapy with curative intent, are used and combined whenever possible. Concomitant chemoradiotherapy is the treatment of choice since it gives better results, but in practice a significant number of patients is not fit for this approach. Therefore, the alternative in unfit patients is sequential chemoradiotherapy or radiotherapy alone. In patients having concomitant chemoradiotherapy there are no results in favour of induction or consolidation chemotherapy. It might be that a novel immunotherapy approach with anti-PD-1 or anti-PD-L1 inhibition will in the future improve the survival rate of this group of patients and patients with the metastatic disease (1-4). The effectiveness of radiotherapy depends on the total radiation dose being delivered accurately. For most tumors there is a dose-response effect, i.e. the higher the dose, the higher the chance of local tumor control and cure. The first trial that in the case of lung cancer demonstrated this relationship was published by Perez et al (RTOG 71-01 trial) (5). In this dose escalation trial, the dose of 60 Gy in comparison with the dose of 50 and 40 Gy was found, evaluated clinically, to have a lower incidence of local failures (33% versus 39% versus 44% to 49%). The survival of patients according to treatment regimen was not statistically significantly different. The one-year and two-year survival rates for all groups were, respectively, 45% and 25%. On the basis of this trial the dose of 60 Gy in 30 fractions (60 Gy/30x) or higher has since that time been the optimal standard radiotherapy treatment, although patient outcomes were objectively very poor. It should be mentioned that from today's perspective the radiotherapy techniques that were then used (2D radiotherapy planning and relatively large tumor/target volumes) are not recommendable nowadays in radiotherapy treatments with curative intent (3,4). The objectively unsatisfactory clinical outcomes in terms of local tumor control, progression free survival (PFS) and overall survival (OS) after radiotherapy +/- chemotherapy treatments are probably the consequence of the inadequate radiation dose to the tumor tissue. However, the usage of higher doses is limited by the radiation tolerance of surrounding normal tissues and organs (3,4). In clinical radiotherapy, the radiation tolerance of normal tissues and organs surrounding the tumor limits the radiotherapy dose that can be given safely. As the dose is increased, the incidence and severity of normal tissue damage rises. When severe, normal tissue damage can produce life threatening morbidities. Multiple parameters such as total radiation dose, fraction size, overall treatment time, volume and type of normal tissues to be irradiated, definition of target volume, and quality control of radiotherapy techniques should be taken into account. A reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in lung cancer as well as other types of cancers. Organs at risk of lung cancer radiotherapy include the lungs, heart, spinal cord, and esophagus. Present knowledge of radiation toxicity is derived from conventional and newer 3D-conformal radiotherapy (3D-CRT) data. The QUANTEC project (6) produced data that are currently used to predict the side effects of radiotherapy and the plausibility of evaluated treatment plans. Before being approved all radiotherapy treatment plans have to be evaluated for the probability of organ-specific radiation toxicity (3,4). Thanks to the evolving radiation imaging and computer technology, a number of innovations in radiotherapy have been introduced in radiotherapy practice within the several past decades. Conventional 2D treatment simulation has been replaced with computer tomography (CT) planning, with volumes delineated according to the International Commission on Radiation Units and Measurements (ICRU) report and ICRU supplements. This CT-based planning together with the possible implementation of other imaging methods such as PET/CT and MRI have enabled more precise target borders and volume determination with the consequence of radiotherapy treatment plans having better tumor dose conformity and sparing the surrounding normal tissues (3,4). Due to a better delineation of tumor margins and reduced rates of radiation-associated toxicity, the current standard radiation treatments based on the implementation of these various technical and technological advances in radiation planning and delivery have allowed the design of clinical studies with radiotherapy dose escalations and modified fractionation schemes. The goal of radiation treatment is to improve clinical outcomes while reducing the damage to the normal tissues. Newer radiotherapy equipment, techniques and treatment planning software can, due to a better delineation of tumor margins and reduced rates of radiation-associated toxicity, allow tumor dose escalation to improve local control and possible tumor cure. Improvements in radiotherapy technique are achieved by using functional images for target definition (PET/CT), 4D-computed tomography (4D-CT), intensity modulated radiation therapy (IMRT) and adaptive radiotherapy. (3,4) Several studies have shown a better response with dose escalation in NSCLC. Doses of up to 74 Gy can be delivered when normal tissue constraints are considered. The phase I/II RTOG 9311 trial reported the outcome of a dose-escalated 3D conformal radiotherapy in stage I-III NSCLCs stratified at escalation dose level according to parameters V20 Gy (percentage of the total lung volume that received > 20 Gy). The results of this trial showed that radiation dose escalation was considered safe when using 3D conformal techniques to 83.8 Gy in patients with a V20 < 25% and 77.4 Gy in patients with V20 between 25 and 36% (7). In the RTOG 0617 trial two schedules were compared: 60 Gy (in 6 weeks) versus 74 Gy (in 7.5 weeks) in a 2×2 design where patients were also randomized to receive or not receive cetuximab. Surprisingly, the higher dose arm was not associated with improved survival at 1 year but, rather, showed a contrary trend. The trial showed an OS of 28.7 months for patients who received standard dose radiotherapy compared with 20.3 months for those who received high dose radiotherapy. Median survival in patients who received cetuximab was 21.3 months compared to 24.0 months in those who did not receive cetuximab (p = .29) (8). The use of IMRT allows clinicians to obtain better radiotherapy planning parameters such as V20 and mean lung dose and to reduce the probability of development of lung toxicity - radiation pneumonitis. As reported in literature, V20 values of 35–37% and the MLD value of 20–23 Gy have been considered safe but 10–15% of patients can still develop a severe radiation pneumonitis when lower doses are delivered (9). The concomitant use of chemotherapy with radiotherapy can achieve a better overall response, albeit with an increased number of treatment related toxicities – esophagitis and pneumonitis in 10 to 40% of patients (7-9). The use of radiotherapy after chemotherapy with delivered escalated doses of 74 Gy and 86 Gy is associated with a higher incidence of bronchial stenosis (4% and 25%, respectively) and can increase when radiotherapy is used concurrently with chemotherapy. For patients with a locally advanced NSCLC stereotactic ablative radiation treatment (SABR) can be used as a boost to the primary parenchymal lesion. SABR treatment was added after the conventional chemo-radiation (60 Gy/ 30 fractions) treatment: the prescription dose varied from 10 Gy in 2 fractions in peripheral lesion to 6.5 Gy in 3 fractions in the central tumors. After a median follow-up of 13 months local control was 82.9% and there were no patients with a radiation pneumonitis grade 4 or 5 (10). Proton therapy is a new potential therapeutic approach to the treatment of NSCLC. Protons have the potential role of reducing the dose to the normal tissue, in particular to the lung and the heart. Initial studies have demonstrated that in patients receiving a concomitant treatment of chemo-radiotherapy the overall survival is influenced by the mean dose to the heart and the lung (3,4,11). As previously described, the univariate and multivariate analysis of RTOG 0617 demonstrated that lung V5, heart V5 and heart V30 were considered predictors of OS. Intraluminal (IL) high-dose rate (HDR) brachytherapy, as the exclusive conformal brachytherapy technique, avoids the previously mentioned dose constraints and could be applied in highly selective cases with significant predominantly endobronchial or endotracheal tumors as a ¨boost” of 10-15 Gy after external beam radiation therapy (EBRT) (60 Gy/30 fractions) or in a palliative setting in recurrent tumors after EBRT in various fractionation schemes according to the American Brachytherapy Society (ABS): 10-15 Gy in one fraction or IL high-dose rate (HDR) alone 22,5 Gy/3 fractions, 24Gy/4 fractions, 30 Gy/6 fractions. Brachytherapy is recommended if there is a collapsed lung at the first presentation because of improved re-expansion rates using IL HDR over EBRT (4,12,13). In conclusion, remarkable technological advances in the planning and delivery of radiotherapy allows us to do more, which raises hopes that this will be translated into improved clinical outcomes for patients having lung cancer. References: 1. Non-Small Cell Lung Cancer Treatment (PDQ®) - Health Professional Version. Available from https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq 2. Small Cell Lung Cancer Treatment (PDQ®) - Health Professional Version. Available from https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq 3. Baker S et al. Radiat Oncol. 2016;11:115. doi: 10.1186/s13014-016-0693-8. 4. Giaj-Levra N et al. Cancer Invest. 2016;34:80-93. doi: 10.3109/07357907.2015.1114121. 5. Perez CA et al. Cancer. 1980;45:2744-53. 6. Marks LB et al. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S70-6. doi: 10.1016/j.ijrobp.2009.06.091. 7. Bradley J et al. Int J Radiat Oncol Biol Phys 2005;61:318–28. 8. Bradley JD et al. Lancet Oncol. 2015;16:187-99. doi: 10.1016/S1470-2045(14)71207-0. 9. Graham MV et al. Int J Radiat Oncol Biol Phys 1999;45:323–9. 10. Feddock J et al. Int J Radiat Oncol Biol Phys 2013;8:1325–31. 11. Oshiro Y et al. J Radiat Res 2014;55:959–65. 12. Stewart A et al. Brachytherapy, 2016:15:1-11. 13. Langendijk H et al.. Radiother Oncol 2001; 58: 257–68.

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Abstract:
A life in Thoracic Oncology – Reflections from a pathologist. While many regard a pathologist as a physician involved in laboratory diagnosis, by definition Pathology is the science or the study of the origin, nature and course of diseases. This broader definition of pathology, which basically encompasses all of the study of medicine, is what first attracted me to the field. After my residency I joined the NCI as a research pathologist studying viral oncology in rodents. However a few years later John Minna gave me the opportunity to return to the study of human cancer when he was appointed the head of the NCI-VA Medical Oncology Branch in Washington, DC, with a focus on lung cancer therapy. Our branch was fortunate to have an outstanding lung pathologist, Mary Matthews who taught me most of what I know about lung pathology. Mary also had a profound effect on the understanding and treatment of lung cancer. In 1973 she established that small cell lung cancer (SCLC) was almost always metastatic at the time of diagnosis, and that surgery was unlikely to be curative.[1]These observations, plus the finding that SCLC showed initial responses to the therapy then currently available, helped establish the fundamental distinction of lung cancers into SCLC and NSCLC categories. The Mary Matthew award for Pathology and Translational Research is one of the distinguished awards of the IASLC and I was fortunate and honored to be the fourth recipient in 2003. John Minna assembled an outstanding group of physicians/scientist many of whom became pioneers in the field of lung cancer. Of interest, all three past and present Chief Executive Officers of the IASLC, Heine Hansen, Paul Bunn and Fred Hirsch, spent time at the NCI-VA Medical Oncology Branch. John preached that new approaches for the therapy of lung cancer were needed, that this would require understanding biology, and to understand biology we needed preclinical models. My job was to establish such models and help “translate” them into clinical care. By the early 1980s we had established and characterized large banks of SCLC cell lines and demonstrated that they expressed the entire neuroendocrine (NE) cell program.[2] The cell lines were widely distributed to the scientific community, and in the absence of reliable tumor tissue sources, became the major source of biologic and molecular knowledge of SCLC. Within that decade our group, largely from the use of cell lines, described chromosome 3p loss, MYC family amplification, RB1 and TP53 loss as being characteristics of SCLC and also discovered the MYCL oncogene. The NCI-VA Medical Oncology Branch later relocated to the Bethesda Naval Hospital, MD. In 1991, John Minna accepted a position at the University of Texas Southwestern Medical Center, Dallas, and I was his first recruitment. Thus, during my long career I have only had two employers! I believe this continuity has helped establish strong, long term collaborations and boosted overall productivity. One of the interests of Mary Matthews and me was the heterogeneity of SCLC. It became obvious to us that the so-called oat cell variant was an ischemic artifact. However we were intrigued by the plasticity of SCLC, with a substantial percentage of cases having abnormal (“variant”) morphologies or combined with NSCLC elements, especially after therapy.[3] The variant morphology and its relationship to NEUROD1 as the driver transcription factor (as opposed to ASCL1 as the driver in typical or “classic” SCLC) has recently been highlighted.[4] By the mid 1980s, advances in SCLC biology and therapy had hit a stonewall, and funding dried up. It was time to move onto NSCLC! We established a large collection of NSCLC cell lines and these also formed much of the basis of our understanding of this disease, although tumor tissues were much more readily available. While cell lines have their pluses and minuses, they are excellent for identifying driver mutations and testing targeted therapies. They contributed to the identification of the role of EGFR mutations in lung cancer.[5, 6] Soon after this discovery we used our international fellows and contacts to perform the first large multinational study of geographic and ethnic variations in mutation frequencies, and also demonstrated that mutations were largely absent in tumors other than NSCLC.[7] The advent of Precision Medicine has highlighted the crucial role of the pathologist. Instead of the image of a pathologist looking at microscope slides in isolation in a basement office, he or she plays a crucial role as an integral part of the diagnostic and therapeutic team involved in every aspect of patient management. The pathologist assumes further responsibilities such as tissue procurement and optimal utilization, triaging scant resources for clinical trial requirements, involvement in molecular testing, performing requested or required immunostaining, establishing tissue repositories etc. Previously clinical decision making required the pathologist only to make a diagnosis of SCLC or NSCLC. Precision Medicine has highlighted the importance of accurate classification of NSCLC. Classification is required for mutation testing, therapy selection (or exclusion) and entry onto histology dependent clinical trials. While the introduction of immunostains has greatly facilitated the classification of poorly differentiated NSCLC, the SEER database indicates that up to 14% of NSCLC may remain unclassified throughout the USA. For these reasons we developed a molecular classifier for NSCLC that can be applied to formalin fixed paraffin embedded (FFPE) materials and small core biopsies.[8] The assay is highly accurate and quantitative, and also provides information on grading and survival. While SCLC languished for three decades, its recent designation as a recalcitrant cancer by the US Congress has resulted in a dramatic resurrection of interest, funding and achievement.[9] This has highlighted the importance of preclinical models for SCLC.[10, 11] I feel very humbled and privileged to have lived through and contributed to the seminal advances in our understanding of the biology and therapy of lung cancer. This would not have been possible without the many wonderful and talented people I have worked with. I am reminded of the quote of Isaac Newton: “If I have seen further than others, it is because I have stood on the shoulders of giants”. References 1. Matthews MJ, Kanhouwa S, Pickren J, et al. Frequency of residual and metastatic tumor in patients undergoing curative surgical resection for lung cancer. Cancer chemotherapy reports Part 3 1973;4:63-67. 2. Gazdar AF, Carney DN, Russell EK, et al. Establishment of continuous, clonable cultures of small-cell carcinoma of lung which have amine precursor uptake and decarboxylation cell properties. Cancer Res 1980;40:3502-3507. 3. Gazdar AF, Carney DN, Nau MM, et al. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res 1985;45:2924-2930. 4. Borromeo MD, Savage TK, Kollipara RK, et al. ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs. Cell reports 2016;16:1259-1272. 5. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500. 6. Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7:169-181. 7. Shigematsu S, Lin L, Takahashi T, et al. Clinical and biological features associated with Epidermal Growth Factor Receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-346. 8. Girard L, Rodriguez-Canales J, Behrens C, et al. An Expression Signature as an Aid to the Histologic Classification of Non-Small Cell Lung Cancer. Clin Cancer Res 2016. 9. Gazdar AF, Minna JD. Developing New, Rational Therapies for Recalcitrant Small Cell Lung Cancer. J Natl Cancer Inst 2016;108. 10. Gazdar AF, Hirsch FR, Minna JD. From Mice to Men and Back: An Assessment of Preclinical Model Systems for the Study of Lung Cancers. J Thorac Oncol 2016;11:287-299. 11. Gazdar AF, Savage TK, Johnson JE, et al. The comparative pathology of genetically engineered mouse models for neuroendocrine carcinomas of the lung. J Thorac Oncol 2015;10:553-564.

Abstract:
WCLC2016 Abstract for Closing Plenary Session A Life in Thoracic Oncology - Reflections on Treatment Advances: Surgery The speaker began his training in Cardiothoracic surgery in 1973 and was appointed as a Consultant in 1979. He will introduce this topic by describing a typical case undergoing surgical treatment for lung cancer in the 1970s, the patient journey and outcomes at that time. From that basis he will detail the changes in the surgical treatment of lung cancer in the last 40 years. This will include: · Changes in the epidemiology of lung cancer. · Improvements in pre-operative selection. · Improvements in the staging process prior to surgery, during surgery and post-surgery. · Differences in surgical approach and the anatomical extent of resection. · Changes in the stage classification over that period. · The establishment of effective adjuvant therapy. · Improved outcomes in morbidity, mortality and survivorship. None of these improvements has been of itself a game changer but collectively they amount to a fundamental change in the surgical management of this disease. A brief mention will be made of advances in the surgical treatment of other thoracic malignancies. Peter Goldstraw

Abstract:
When I commenced training in radiation oncology in 1973, there were no CT scanners, calculations were done with slide rules, and chemotherapy, let alone combined modality therapy, had no established role in the treatment of non-small cell lung cancer. An influential trial published in the Lancet in 1971(1) had shown no difference in survival whether patients were randomized to radiotherapy, chemotherapy, a combination of the two or a policy of wait-and–see. Yet within 30 years, the standard of care for patients with inoperable lung cancer being treated for cure, both small cell and non-small cell, had, ironically, become, and remains, concomitant chemotherapy and radiotherapy. The outlook for patients generally regarded as incurable at the outset of my career is that up to one in three selected patients can now expect to live five years as a result of chemoradiation. Patients with stage I non-small cell lung cancer can have their cancer successfully ablated by non-invasive stereotactic radiotherapy in 90% of cases. The developments which led to these changes can be grouped according to three main themes: the impact of the computer revolution; a better understanding of the natural history and biology of the disease, and the introduction of mutimodality therapy. The computer revolution: imaging, treatment planning and delivery Better identification and delineation of the tumor are critical to the success of radiotherapy, in particular avoidance of the catastrophic “geographic miss”. Without computers, the CT and hybrid PET/CT scanners could not have been possible. These dramatically improved the accuracy of staging as well as providing 3D information on the relationship of the soft tissue target to the nearby dose-limiting organs at risk. As computing power increased it became possible to create 4D images of moving tumours, and to image the target with on-board CT scanners attached to the linac immediately before treatment, so making image guided stereotactic ablative radiotherapy possible. Powerful computerised treatment planning systems are now able to create complex dose distributions conforming to the irregularities of any target volume, and to provide dose-volume metrics predictive of risks of normal tissue damage. Improved understanding of the natural history and biology of the disease The recognition that the central nervous system is a sanctuary site which can harbour metastatic disease leading to treatment failure in spite of successful chemotherapeutic eradication of extracranial disease, particularly in small cell lung cancer, led to the introduction of prophylactic cranial irradiation. The British study of continuous hyperfractionated accelerated radiotherapy (CHART) which was given over 12 days to patients with inoperable non-small cell lung cancer resulted in better survival than treatment given over six weeks, even though the total dose was lower. This trial provided clinical support for the notion of treatment induced accelerated repopulation, and reinforced the principle that total treatment times should be kept short in both small cell and non-small cell lung cancer, both when radiotherapy is used alone, and when in combination with chemotherapy. Multimodality therapy The limitations of single modality therapy for a disease with a high propensity for developing genetically determined resistance have long been recognised, and have stimulated the development of strategies simultaneously employing non-cross resistant therapies to maximise tumor cell kill, in line with the principles espoused by Goldie and Coldman.(2) The use of concomitant platinum based chemotherapy with high dose radiotherapy is now well established by meta analysis as improving survival of both non-small cell and small cell lung cancers, but it is also more toxic. Amelioration of these toxicities represents a major challenge for the future. Future directions It is likely that the technical progress in radiation treatment planning and delivery is close to a plateau, and that future progress will depend more on understanding the biology of the disease and its response, and that of the normal tissues, to radiation damage. Biomarkers of response and toxicity, so spectacularly harnessed to advantage by our medical oncology colleagues, are desperately needed to tailor the radiotherapy prescription to the needs of each individual and their cancer. Finally, it is evident that in many jurisdictions, including industrialised wealthy nations, that many patients are either receiving substandard radiotherapy that might increase their chances of cure, or are not receiving treatment at all.(3) Unless these problems can be addressed, the benefits of the remarkable advances in technology and biology documented above will shamefully be restricted to only a fraction of those afflicted with locoregional disease. 1. Durrant KR, Berry RJ, Ellis F, Ridehalgh FR, Black JM, Hamilton WS. Comparison of treatment policies in inoperable bronchial carcinoma. Lancet. 1971;1(7702):715-9. 2. Goldie JH, Coldman AJ, Gudauskas GA. Rationale for the use of alternating non-cross-resistant chemotherapy. Cancer Treat Rep. 1982;66(3):439-49. 3. Vinod SK. International patterns of radiotherapy practice for non-small cell lung cancer. Semin Radiat Oncol. 2015;25(2):143-50.

Abstract:
Lung cancer is a leading cause of cancer death in the world.　The survival benefit of chemotherapy was rarely observed in NSCLC until the development of Cisplatin. Platinum doublets including 2nd/3rd generation cytotoxic drugs showed minor prolongation of survival but the effect reached a plateau. JCOG conducted key RCTs to develop new standards against SCLC but a breakthrough has not been observed yet. Two recent major therapeutic advancements in NSCLC are immunotherapies to inhibit immune checkpoints and development of targeted drugs for driver mutations. Translational Research in Immune Checkpoint inhibitors Immunotherapy of cancer has a long history without success because of wrong strategy of immune stimulation with non-specific immunostimulators, biological response modifiers and recently by peptide antigens. After introduction of idea on immune checkpoint inhibition by Dr. James Allison, the studies of this fields were dramatically activated. Currently two anti-PD-1 antibodies such as Nivolumab and Pembrolizumab have been approved for the treatment of NSCLC based on reproducible effects of tumor shrinkage and survival benefit. In second line treatment, both antibodies significantly improved survival compared with standard care of cytotoxic chemotherapy irrespective of patient selection. Recent press release announced that Nivolumab failed to demonstrate benefit for PFS compared to cytotoxic chemotherapy (CheckMate-026), on the other hand Pembrolizumab demonstrated superior PFS and OS (KEYNOTE-024). Both of the trials patient selection was done based on PD-L1　expression in lung cancer cells. In spite of positive data on survival, RR in various trials against advanced NSCLC with or without prior chemotherapy ranges from 15-25% for both drugs and median survival is almost same in anti-PD1 Ab and cytotoxic drugs. The most important issue will be how to concentrate responsive patient population or how to eliminate in effective patients. Although there is a tendency of correlation between PD-L1 expression and objective response/survival, responders to Ab are experienced even in PD-L1 negative patients. There are many problems in PD-L1 screening. There is no comparative data of various PD-1 tests used in various clinical trials. Each PD-1 test uses different antibody. Each test uses a different definition and cut off point that defines PD-1 positivity. There is no data on best sample, paraffin-fixed vs fresh tissue, primary site tumor vs metastatic tissue. PD-1 expression is not stable and influenced by many factors. There is no reliable validation and standardization. In tumor cells, mutation burden may influence on antigenicity. In colorectal cancer, microsatellite instability has related with response to anti-PD-1 antibody, but it is not yet clear whether mutation burden really increases antigenicity. CD8 lymphocytes infiltration is also considered to be one of the biomarkers for anti-PD-1 Ab response. However, it is too objective and seems to be quite difficult to quantify CD 8 lymphocytes infiltration. The most important thing will be the function of killer T lymphocytes which can respond to target antigens and to kill tumor cells. The best method may be quantitative measurements of cytotoxicity in killer T cell on tumor cells. The techniques to demonstrate this process are mandatory for successful patient selection in the treatment with anti-PD-1 antibody. Translational Drug Development for Precision Medicine Recent development of molecular target drugs in lung cancer　really reflects progress of translational studies. EGFR-TKIs are one of the most important drugs and changed concept of treatment of lung cancer. Finding on many rare driver mutations forced to reclassify lung cancer to various genomic subtypes. Innovative technologies for genomic medicine changes one size fit medicine to precision medicine. For discovery of drugs to each genomic subtype of lung cancer, nationwide and global screening network should be mandatory. In Japan LC-SCRUM Japan leaded by Dr. Koichi Goto, National Cancer Center Hospital East, started in February 2013 to find out new seeds against lung cancer by the support of government.. At the beginning, tumor tissues were analyzed for ALK/ROS1/RET fusions using RT-PCR in EGFR –Mt negative patients and the detected fusions were confirmed by FISH. From March 2015, multiplex diagnostic kit using NGS was introduced and this project expanded as SCRUM-Japan including other histological types of lung cancer such as SQ and SM as well as GI malignancy. 14 pharmaceutical companies started to support this project. No. of institutions joined in the network increased to 200 In Non-SQ NSCLC, 159 and 96 for SQ and SM, respectively on March, 2016. More than 2,500 samples were analyzed. Rare mutations including ROS(91), RET(54) and ALK(40) fusions, ERB2 mutation/amplification(48), BRAF mutation(16), MET amplification/ex14 skip(16) and PIK3A mutation(22) have been screened in 287 Non-SQ-NSCLC patients and 67(23%) have been accrued to more than 12 clinical trials. In LURET trials against RET fusion gene + patients, 19 patients have been accrued and 17 are eligible. The response rate of vandetanib was 53%and PFS was 4.7 months. In 0012-01 trial against ROS fusion gene + patients, 129 patients (74 from china, 26 from Japan, 15 from Taiwan and 12 from Korea)has been accrued. Response rate of crizotinib was 69%in 127 evaluable patients. J-AlEX trial was a phase III randomized controlled trial comparing alectinib(ALE) and crizotinib(CRI) in ALK-positive NSCLC. Response rates for ALE and CRI were 85.4% and 70.2% respectively. PFS was not reached and 10.2 months(P<0.0001), respectively. Other clinical trials are ongoing. Samples from SQ and SM are increasing and interesting mutations and amplifications have been detected in these materials. Accordingly this nationwide and population enrichment screening system enabled various rare driver mutations to be efficiently detected in lung cancer, contributing to the rapid accrual of matched patients in translational clinical trials.

Abstract:
Chemotherapy has long been the only available systemic treatment for Non-Small Cell lung Cancer. In the late 70’s, there were a multitude of triplets and quadruplets with response rates ranging from 20-35% in patients with stage IV disease. In 1980, cisplatin, a cytotoxic agent initially developed for germ-cell tumors, showed some activity, mostly when combined with a vinca-alkaloïd or with etoposide. At the time Vinorelbine was registered by the FDA in 1994, alone or in combination with cisplatin, only 3 drugs were approved for NSCLC, nitrogen mustard, methotrexate and doxorubicin! Metastatic Disease The individual data-based meta-analysis published in 1995 established the superiority of chemotherapy over supportive care in patients with advanced NSCLC. These results have been recently updated and confirmed in 2714 patients from 16 trials with an overall survival benefit of 9% at 1 year. Chemotherapy also improves quality of life and symptom control in patients with good performance status. It is classically recommended to use platin compounds (mostly cisplatin and carboplatin) in combination with third generation agents including vinorelbine, gemcitabine, taxanes (paclitaxel, docetaxel, nab-paclitaxel) or pemetrexed (in non-squamous NSCLC). Integrating palliative care at an early stage of the treatment also prolongs survival and improves quality of life. Second line chemotherapy with docetaxel or pemetrexed has also been demonstrated active even if the benefit on overall survival remains modest. The use of biological markers such as ERCC1, RRM1, beta-tubulin or thymidilate synthase has not yet proven efficacy on the choice of cytotoxic agents. Maintenance: Up to 2009, it was generally accepted that 4 to 6 cycles of induction chemotherapy followed by a rest till progression were the standard. The switch to a new drug as maintenance after 4 cycles of a platin-based doublet showed a benefit for PFS and OS. Maintenance is now considered a standard in the management of metastatic NSCLC. Chemo-radiotherapy for locally advanced disease: The benefit obtained with radiotherapy and chemotherapy given sequentially in locally advanced inoperable NSCLC is modest but significant and well established. Several randomized trials comparing radiotherapy-chemotherapy given sequentially or concomitantly have suggested a better outcome when both modalities were given early and simultaneously. A meta-analysis based on individual patient data from published and unpublished randomised trials which compared radiotherapy alone with the same radiotherapy combined with concomitant cisplatin- or carboplatin-based chemotherapy was recently performed. The analysis was based on 9 trials including 1764 patients. The hazard ratio of death among patients treated with radio-chemotherapy compared to radiotherapy alone was 0.89 (CI 95%: 0.81-0.98; P = 0.02) corresponding to an absolute benefit of chemotherapy of 4% at 2 years. There was some evidence of heterogeneity among trials and sensitivity analyses did not lead to consistent results. The available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy in combination with radiotherapy. Adjuvant chemotherapy: In the meta-analysis published in 1995, a 13% reduction in the risk of death was observed, suggesting an absolute benefit of 5% at 5 years with adjuvant chemotherapy. These results constituted the rationale for a new generation of randomized studies with platinum-based regimens. The LACE meta-analysis, which was reported at ASCO 2006, pooled a total of 4584 patients accrued in the five largest cisplatin-based adjuvant trials launched after the results of the meta-analysis. It confirmed the benefit of adjuvant chemotherapy with a 5.3% improvement of survival at 5 years (p=0.0043). Disease-free survival was also improved (5.2% at 5 years, p<0.0001). There was a negative effect of adjuvant chemotherapy for stage IA. The risk reduction was 8% for stage IB, 17% for stages II and III. The effect of chemotherapy did not vary according to age, gender, PS, type of surgery and histology. In parallel, the adjuvant UFT meta-analysis also confirmed a significant advantage of the drug compared to control in 2003 Japanese patients (p<0.001). The individual-data-based meta-analysis was updated in 2007. It confirmed the significant effect of postoperative chemotherapy, with or without postoperative radiotherapy. Neoadjuvant chemotherapy : Several phase II trials have been carried out in the 80’s to evaluate the benefit of preoperative chemotherapy in operable NSCLC with encouraging results. In the mid 90’s, two randomized phase III trials had a significant impact on the medical community due to their impressive results. Both trials randomized 60 stage IIIA patients and were interrupted after positive interim results were observed. Only two published randomized phase III studies comparing front-line surgery to pre-operative chemotherapy followed by surgery accrued the number of patients that were initially planned: a French study that included 373 patients and the Medical Research Council LU22 trial that included 519 patients. None of the large randomized studies could demonstrate a significant advantage in favor of pre-operative chemotherapy. A recent individual patient data-based meta-analysis of pre-operative chemotherapy trials has included 2385 patients from 15 trials. A HR of 0.87 (CI 95%: 0.7_–0.96, p=0.007) was observed, equivalent to an absolute improvement in survival of 5% at five years, similar to the benefit observed with postoperative chemotherapy. Preoperative or postoperative chemotherapy? A comparison of preoperative versus postoperative chemotherapy has been did not show any difference. In fact, the key issue may be to determine which patients should be treated with adjuvant and/or neo-adjuvant therapy. The neo-adjuvant approach offers a unique opportunity to test new drugs and to compare the tumor characteristics prior to and following induction therapy. Developing molecular based therapeutic strategies will certainly be one of the major challenges over the next few years. Several randomized adjuvant studies have recently been initiated in Europe and in America, based on the molecular characteristics of patients tumor. In conclusion, chemotherapy remains the main systemic treatment for most patients with lung cancer and the only one able to increase the cure rate. Unfortunately, very few drugs have been developed in the last decade in spite of a clear unmet medical need. A better individual selection of drugs/drug combinations according to pharmacogenomic data might encourage the community to optimize the use of cytotoxic agents.

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Abstract:
The past decade has seen more advances in diagnosis and management of lung cancer than were available in the previous 30 years. Fifty years ago, the association of cigarette smoking in lung cancer was firmly established by the Surgeon General's report in the United States. During the past decade, major efforts by IASLC and other organizations have greatly reduced the use of tobacco and, thus, we will be seeing a decrement in morbidity and mortality from lung cancer. However, in the United States last year, there were still 228,000 new cases and 160,000 deaths from lung cancer. It remains the number one cause of cancer death in both American men and women, and the same is true in most developed and developing countries. Over 28% of all cases of cancer death in the United States are due to lung cancer. IASLC has been a leader in updating the TNM classification for non-small cell lung cancer. This allows for uniformity of data results in surgical and adjuvant studies. Cisplatin-based adjuvant chemotherapy has been demonstrated to improve the surgical cure rate by 5-10%. In the future, we hope to be able to identify by molecular, rather than just clinical characteristics, those patients with resected lung cancer who are cured with surgery and do not need to be subjected to adjuvant chemotherapy, as has been similarly accomplished in breast cancer. Also, we hope to have better definition of tumors that are inherently platinum resistant and, therefore, would need alternative strategies to try to improve the surgical cure rate. For the last two decades of the 20th century, chemotherapy has been the backbone for treatment of stage IVB lung cancer. Most studies have been built around platinum combination chemotherapy. Earlier studies pre-platinum utilized inactive drugs such as cyclophosphamide and doxorubicin. In the 1980s, cisplatin and etoposide was a common platinum doublet, and in the 1990's, carboplatin + paclitaxel. A review of phase III trials in North America from 1973-1994 demonstrated very sobering results. Thirty-three trials in 8,434 patients were performed and 23 of these 33 included a platinum compound. Only 5 of the 33 trials demonstrated a statistically significant difference in survival with a median increase of 2 months (range 0.7 to 2.7 months). It thus became clear that we need to personalize therapy rather than giving all patients the same chemotherapy. Modest success was seen by adding Bevacizumab to carboplatin + paclitaxel. Major advances have been made during the past decade with the identification of specific mutations that can be therapeutically exploited. EGFR and ALK were the first to be identified and subsequently ROS-1. Molecular targeted agents demonstrated spectacular responses in the great majority of patients, compared to the usual 25% brief responses that were achieved previously with platinum-based combination chemotherapy. These driver mutations were predominantly in adenocarcinomas and non-smokers or never smokers. More recent mutations have included smokers and non-smokers such as BRAF V600E and MET Exon-14 skipping mutation which can be seen in smokers as well as non-smokers. During the past five years, immunotherapy has been an exciting new addition to the armamentarium for treatment of patients with metastatic lung cancer. Immune checkpoint inhibitors are still in the nascent phase and the optimal duration of therapy for stage IVB disease, combination with other immunotherapeutic agents, chemotherapy, or radiotherapy, as well as use of adjuvant therapy, will be awaited with eager anticipation. Exciting new technology such as CRISPR-cas9 to gene edit PD-1 holds great potential future promise to make these immune checkpoint inhibitors more effective in a larger percentage of patients with lung cancer, as well as those responses being more durable.

Abstract not provided