Virtual Library

Background:
Lung tumours often exhibit large and unpredictable motion that can severely compromise radiotherapy outcomes. Markerless tumour tracking can enable wide access to motion-adaptive radiotherapy, negating the risks and costs associated with implanting markers. The main barrier to markerless tumour tracking is the inferior tumor visibility on x-ray images due to overlapping anatomic structures. The aim of this study is to develop a markerless tumor tracking method for lung radiotherapy using intrafraction x-ray imaging.

Methods:
The markerless tumour tracking method (Figure1a) consists of four steps: (1) Building a tumour and anatomic model from the cone-beam CT (CBCT) acquired prior to treatment, (2) Using the anatomic model to remove the contribution of anatomic structures on intrafraction x-ray images, (3) Locating the tumour on the intrafraction 2D x-ray image via template matching using the tumour model, (4) Determining the tumour 3D position by a Kalman filter. The proposed method was retrospectively validated on (i) 11 CBCT scans from four patients with central tumours, and (ii) a kV fluoroscopic scan during a stereotactic ablative radiotherapy (SABR) treatment from the Light SABR trial (NCT02514512). Tracking errors were estimated using the motions of markers or beacons implanted near the tumours. Figure 1



Results:
Markerless tumour tracking successfully tracked tumours in all cases at every imaging angle. The mean 3D tracking error ranged from 1.8-4.1mm for the 11 CBCT scans, and was 3.0mm for the SABR case. Compared with the current standard of care, i.e. a single estimation of tumour position prior to treatment from the pre-treatment CBCT, markerless tumour tracking reduced tumour localization error by 0.9-7.9mm. Tracking errors in the left-right, superior-inferior, and anterior-posterior directions are shown in Figure1b.

Conclusion:
A markerless tumour tracking method was developed and shown to improve tumour localization accuracy in 12 lung cancer cases. This method can potentially enable wide access to motion-adaptive radiotherapy.

Background:
MLC tracking is an emerging technology to improve tumor targeting and reduce normal tissue irradiation during radiotherapy. The purpose of this work is to present the early clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung cancer.

Methods:
Full ethics approval through an Australian ethics board has been received for recruitment of 20 patients with stage 1 lung cancer or lung metastases into the MLC tracking clinical trial (NCT02514512). To date, seven recruited patients have each had three electromagnetic beacons inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For comparison a conventional motion-encompassing SABR plan was generated with PTV expanded 5mm from a 4DCT-derived internal target volume. Treatment was delivered using a standard linear accelerator using in-house developed software to continuously adapt the MLC motion based on the Calypso beacons’ movement. Tumor motion, treated volume and reconstructed delivered dose were compared between MLC tracking and conventional motion-encompassing treatment planning.

Results:
All seven patients have been treated successfully with MLC tracking (29 successful fractions). The MLC tracking PTV for all patients has been smaller than with ITV based planning (range 12% to 41% reduction, or 2 to 18 cm[3] with MLC tracking). Subsequent reductions in normal lung dose were observed. Tumor motion was seen to vary in motion range from the planning 4DCT during treatment; significantly, larger motion was observed during treatment that exceeded standard PTV boundaries. Reconstruction of delivered treatments confirmed the accurate delivery of MLC tracking, with 100% prescribed dose delivered to the GTV.Figure 1



Conclusion:
The first treatments with MLC tracking have been successfully performed in seven lung cancer patients. Reductions in treated volumes were observed, which translated to reductions in delivered lung dose.

Background:
Objectives: In lung cancer patients treated with image-guided radiotherapy we use daily Cone-Beam CT (CBCT) guidance for setup verification and to check on intra-thoracic anatomical changes (ITACs). ITACs like tumor baseline shifts, the occurrence or dissolving of an atelectasis, tumor progression or regression, pleural fluid- and infiltrative changes have been reported in 72% of lung cancer patients (Kwint M R&O 2014) during the course of irradiation. A traffic light protocol has been in use by the radiation technologists since 2010 to classify anatomical changes seen on the CBCT with anticipated different influences on the dose distribution using 4 action levels. The purpose of this study was to quantify how often the ITACs occurred in daily clinical practice and for which action level.

Methods:
All lung cancer patients irradiated in 2015 (excluding stereotactic treatments) with a dose >44 Gy were included. All patients had a daily CBCT guided online correction protocol and the traffic light action level of each CBCT was recorded. The following action levels have been defined: code red for immediate consultation with the physician before beam-on, code orange for a decision on the notification of the physician before the next fraction, code yellow to inform the physician; no action is required- and green for no change so no intervention necessary. We also analyzed the percentage of patients that received a new planning-CTscan and/or a new treatment plan.

Results:
In 2015 a total of 299 lung cancer patients were conventionally irradiated with radical intent and 5971 CBCT scans were made. Of these CBCTs 51% were scored as code green, 24% as code yellow, 24% as code orange and code red in less than 1% of the CBCTs. Forty patients (13%) had a new treatment plan, of which 34 patients (11%) had a new planning CT-scan and 6 patients (2%) had a new treatment plan on the original planning CT-scan.

Conclusion:
Image-guided irradiation for 299 conventionally fractionated lung cancer patients (>44 Gy) in 2015 revealed lTACs in 25% of the CBCT’s made and a physician’s decision on the notification was necessary. A total of 13% of the patients treated received an unscheduled adaptive treatment plan during the course of treatment. The traffic light protocol in daily clinical workflow worked well as a tool to prioritize a physician’s decision based on the ITACs seen on the CBCT images.

Abstract not provided

Background:
Nivolumab has been recently approved by the FDA as a 2[nd]-line treatment of NSCLC. The data regarding its efficacy in the real-life setting is lacking.

Methods:
260 consecutive patients with advanced NSCLC treated with nivolumab at five cancer centers in Israel between January 2015 and March 2016 were observed for OS and toxicity. OS was analyzed by the Cox proportional-hazards regression model.

Results:
Patient baseline characteristics: median age 67y (range 41-99); males 68%; smokers 76%; ECOG PS ≥2 46%; Non-sq/Sq/other 70%/23%/7%; KRASm/EGFRm/ALK+/other genetic aberration/none/NA 7%/5%/0%/4%/42%/42%; brain metastases 21%; liver metastases 21%; treatment (Tx) line: 1st/2nd/3rd+-line/NA 6%/64%/26%/4%. Median duration of follow-up was 4.3 mo (range 0.1-13.8); median Tx duration was 2.7 mo (range 0.1-15.5); median number of Tx cycles delivered was 6 (range 1-26). 130 (50%) patients died; median OS comprised 6.6 mo (95%CI 5.6-8.4). In univariate and multivariate analysis, the only variable which significantly correlated with OS was ECOG PS (table 1). Median OS of patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 8.6 mo and 3.5 mo, respectively. Safety data is presented in table 2. Figure 1Figure 2





Conclusion:
Nivolumab has reasonable efficacy and good safety profile in the real-life setting. ECOG PS ≥2 is associated with poor prognosis.

Background:
Patients with non-small cell lung cancer (NSCLC) display a wide spectrum of oncologic outcomes, suggesting significant underlying biologic diversity. However, current radiotherapeutic management is largely homogeneous for a given stage, To advance genotype-directed radiotherapy in NSCLC, we sought to identify genetic determinants of radioresistance by leveraging cancer genomic data with a recently developed high-throughput platform for measuring radiation survival.

Methods:
We used our recently validated high-throughput proliferation assay to profile 104 lung cancer cell lines, including 89 NSCLC and 15 small cell lung cancer (SCLC) lines, for radiation survival. Survival curve analyses permitted quantitative assessment of radiosensitivity. Genomic correlates of radiosensitivity were explored by calculating the information-based similarity metric and correlating genomic parameters by accessing Oncomap data from the Cancer Cell Line Encyclopedia, the COSMIC database of the Cancer Genome Project, and The Cancer Genome Atlas.

Results:
Radiation survival across lineages reflected clinical experience regarding differential response to fractionated radiation inasmuch as lung squamous cell carcinoma and adenocarcinoma (ACA) had similar radiosensitivity, whereas SCLC and carcinoid were, respectively, more and less radiosensitive. Importantly, radiosensitivity varied more within a lineage than across lineages, with a 6-fold difference in integral survival among ACA lines. Correlation with cancer genomic data revealed BRAF mutations within the most resistant ACA lines (P = 0.0097, FDR = 0.957). A majority of the mutations identified by our analysis have been previously annotated by The Cancer Genome Atlas lung ACA dataset and all hypermorphic mutations identified were located in the highly conserved kinase domain. The majority of mutations have been known to enhance kinase activity in melanoma in a fashion analogous to the well-known BRAF V600E mutation. In line with these findings, we showed that kinase domain mutations were hypermorphic as measured by MEK and ERK1/2 phosphorylation. We also showed that exposure of wild type BRAF cells to radiation results only in a transient activation of MEK and ERK1/2. The MEK inhibitor selumetinib selectively decreased the growth of cells with kinase domain BRAF mutations and sensitized these cells to radiation.

Conclusion:
BRAF mutations are associated with radiation resistance in lung ACA. Our data nominates MEK inhibitors, a drug class currently in clinical use, as a targeted therapeutic in select BRAF-mutant lung ACA. Further investigation has the potential to yield an additional genotype-directed therapy that could impact up to 4-6% of patients with lung ACA, a frequency comparable to that of ALK rearrangements (4%) or EGFR mutations (10%).

Abstract not provided

Background:
FDG-PET/CT is the gold-standard for non-small cell lung cancer (NSCLC) diagnosis, staging and tumour delineation prior to chemo-radiation therapy (CRT). FDG-PET is superior to CT for subsequent response assessment. Sequential interim metabolic and proliferative tumour response assessment with FDG and 3'-Fluorothymidine (FLT) respectively, prior to and during CRT is novel and may predict outcome.

Methods:
Patients with FDG-PET-stage I-III NSCLC who were prescribed radical chemo-RT (60 Gy in 30 fractions @ 5/wk) were enrolled. FDG and FLT PET/CT scans were performed at baseline and at weeks 2 and 4 of CRT. Intra-treatment tumour response judged by reduction in FDG and FLT uptake was categorised as complete (CR)/partial response (PR), stable (SD) or progressive disease (PD) using EORTC criteria. Overall Survival (OS) and Progression Free Survival (PFS) were measured relative to intra-treatment scan dates and plotted using Kaplan-Meier curves. Univariate Cox regressions were used to calculate associations between 1. SUVmax of baseline FDG and FLT GTV and 2. intra-treatment FDG and FLT response with patient outcomes (OS and PFS).

Results:
Sixty patients were recruited between 2009-13; male 62%; median age 66 years, adenocarcinoma (42%). Two-year OS and PFS were 0.51 and 0.26 respectively. Of 332 PET/CT scans analysed, study scans provided additional information to FDG~BL~ in 21 (35%) patients. Distant metastasis was detected in 3 patients on FLT~BL~ and in 2 patients on FDG/FLT~wk2~ changed treatment intent to palliative. Loco-regional progression during RT was observed in 5 (8%) patients, prompting larger RT fields. FLT~wk2~ response (SD vs CR/PR vs PD) was associated with OS [HR (95%CI) 1 vs 2.02 (0.87, 4.65) vs 20.09 (4, 114), p=0.012] and PFS [1 vs 2.01 (0.92,4.37) vs 32.41 (3,348), p=0.024]. Associations between the baseline FDG and FLT SUV~max ~and patient outcomes were not significant, including OS where FDG SUVmax HR [95% CI] was 1.04 [0.98, 1.10], p=0.25 and FLT SUVmax HR [95% CI] was 1.07 [0.93, 1.22], p=0.33.

Conclusion:
Tumour response on FLT~wk2~ was associated with OS and PFS. The possible association between worse clinical outcomes and early suppression of FLT uptake during CRT may be a result of repair of tumour DNA damage. Baseline FLT, FLT~wk2~ and FDG~wk2~ detected rapid distant and loco-regional progression in 10 (17%) patients prompting changes in treatment intent and RT fields.

Background:
Treatment-related toxicity is more common following stereotactic ablative radiotherapy (SABR) for central lung tumors, than is the case for peripheral tumors [Tekatli 2015]. Further reductions in doses to critical central structures are possible using respiration-gated SABR delivery, but insertion of fiducial markers for gating is also associated with toxicity. We describe a novel approach for clinical delivery of breath-hold gated SABR under continuous MRI-guidance.

Methods:
The MRIdian® system permits tumor visualization at 4 frames/second during treatment delivery, with radiation beam-holds whenever the target is outside a prespecified gating window. The gating procedure is as follows: a 17 second inspiration breath-hold MR scan is performed for planning before each SABR fraction (resolution 1.6×1.6×3.0 mm). Image registration is performed, and contours adapted when necessary. A 3mm PTV margin is added, and planned dose distribution recalculated for the ‘anatomy of the day’, and reoptimized. A sagittal plane is chosen for tumor tracking and gating, with a planning target margin of 3 mm. The sagittal tracking view from the MRIdian console is projected on a MR-safe monitor (Cambridge Research), and patients can continuously observe the tracking image using a mirror inside the bore.

Results:
Since May 2016, 30 fractions of MR-guided gated delivery have been performed in 5 cancer patients with 6 central tumors. All MR-based breath-hold PTV’s were smaller (mean 19.8 ± 13.3 cc) than a conventional free-breathing, motion-encompassing approach (mean 36.1 ± 21.9 cc). Plans of a single case are shown in Figure 1. Video-assisted visual feedback achieved a breath-hold gating efficiency of 52% (range 27-88%).Figure 1



Conclusion:
For high-risk SABR cases, use of MR-guided, video-assisted breath-hold gated SABR delivery constitutes a novel treatment method, allowing for minimization of mobility- and setup margins, and for improved verification of SABR delivery. Data from additional patients undergoing treatment will be presented.

Background:
Worldwide lung cancer is the biggest cause of cancer mortality (Cancer Research UK, 2012) and is the UK’s second most commonly diagnosed malignancy (Macmillan Cancer Support, 2013). Early detection and treatment significantly improves five year survival rates but curative treatments can impact on patients’ health and wellbeing. To date little research has been conducted to establish the support needs and recovery patterns of health and wellbeing among lung cancer patients treated with curative intent radiotherapy. This limits our ability to identify those most at risk of poorer health and wellbeing outcomes and target services effectively to support patients better. This study assesses the feasibility of collecting patient reported outcomes measures (PROMs) and clinical details to understand recovery after curative intent radiotherapy treatment for lung cancer.

Methods:
This mixed methods study used a prospective, longitudinal cohort design. Eligible patients awaiting curative intent radiotherapy were recruited from six UK sites between October 2015 and June 2016. Questionnaires were completed before undergoing radiotherapy and 3 months later. The questionnaires included validated patient reported outcome measures, including quality of life, symptoms, social support, wellbeing and socio-demographic details. Participants’ medical details were collected by healthcare professionals (HCPs) including cancer type, stage, treatment, and comorbid conditions. Study procedures were evaluated in a qualitative process evaluation.

Results:
Of 229 eligible patients, 136 consented to the study with 73% uptake of those approached. A further 13 patients provided reduced consent to collect demographic and medical information only. Preliminary results: response rates 76% at baseline and 65% at 3 months. Of baseline responders: 59% were male; the median age was 70 years; 29% lived alone; 61% were home owner-occupiers and 20% were current smokers. Baseline EORTC-QLQ-C30 results showed a mean global health status score of 56.6 and patients were most affected by dyspnoea and fatigue with mean scores of 48.8 and 45.0. These are in line with expected scores based on reference data. To date 9 HCPs, 7 patients and 2 stakeholders have been interviewed as part of the process evaluation, study processes and procedures are deemed acceptable to participants.

Conclusion:
This study demonstrates it is feasible to recruit a cohort of lung cancer patients prospectively to assess wellbeing and patterns of recovery following radiotherapy. This novel approach to understanding lung cancer patients’ experiences of survival will enhance our ability to target appropriate and timely support to those most at risk of poorer health and wellbeing.

Abstract not provided

Background:
Our laboratory has demonstrated the augmented anti-tumor efficacy of intrapleurally administered cancer-antigen mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T cells (Sci Transl Med 2014), and translated the approach to a clinical trial (NCT02414269) for thoracic malignancies. We hypothesized that regionally administered MSLN CAR T cells can circulate systemically to achieve abscopal anti-tumor efficacy in an antigen-specific manner, and the abscopal efficacy can further be promoted by tumor-targeted radiation therapy (RT).

Methods:
Using optimized protocols that would permit non-necrotic, well-vascularized tumor growth in pleura, chest wall, peritoneum and flank, tumors were established in immunodeficient (NOD/SCID gamma) mice using mesothelioma or lung adenocarcinoma (LAC) cells. Tumor burden progression, MSLN-targeted CAR T-Cell accumulation at primary and distant tumors was monitored by noninvasive bioluminescence imaging (BLI) and tumor volume measurements.

Results:
A single dose of MSLN CAR T cells administered intrapleurally proliferated (Figure 1A left panel), circulated extrapleurally and accumulated at abscopal sites, including the lymph nodes, chest wall, peritoneum, and flank within 3-5 days, with subsequent T-cell proliferation at abscopal sites (Figure 1A right panel). Primary tumor-targeted, single-dose, thoracic RT prior to T-cell administration augmented T-cell accumulation as demonstrated by BLI (Figure 1B) and tumor T-cell quantification (p<0.01). In a mouse model of primary pleural, abscopal antigen-expressing and non-expressing flank tumors (Figure 1C), a single, low-dose, non-cytotoxic thoracic RT enhanced abscopal site CAR T-cell accumulation that resulted in tumor regression (p=0.01; Figure 1D). Figure 1



Conclusion:
Regionally administered mesothelin-targeted CAR T cells proliferate and eradicate the primary tumor, accumulate and demonstrate anti-tumor efficacy at abscopal sites prior to eradication of the primary tumor in an antigen-specific manner. A single low-dose primary tumor-targeted radiation therapy promotes scopal and abscopal anti-tumor efficacy. These results provide rationale to initiate a clinical trial of combination regional therapies with radiation therapy and CAR T cells.

Background:
Immune checkpoint inhibitors (ICPIs) nivolumab and pembrolizumab have been FDA-approved in non-small cell LC (NSCLC). Current IHC based diagnostics are challenged by assay and slide scoring issues and modest predictive value, and more robust and comprehensive biomarkers of ICPI efficacy are needed. A discovery set of 64 NSCLCs treated with ICPIs suggested that high TMB (≥15 mutations/Mb) significantly correlated with longer time on drug (Spigel et al., ASCO 2016, Abstract:9017).

Methods:
Comprehensive genomic profiling (CGP) was performed during the course of clinical care. TMB was assessed as the number of somatic, coding, base substitution and indels per Mb of genome. Microsatellite instability-high (MSI-H) or stable (MSS) status was determined using a proprietary algorithm.

Results:
15,529 LCs: 66% adenocarcinoma, 1% sarcomatoid, 14% NSCLC NOS, 11% squamous, 5% small cell, and 2% large cell were assessed. TMB was similar across all lung histologies (median: 6.3, 8.1, 9.0, 9.9, 9.9, and 10.8); the median was 7.6 for all LC cases (TMB ≥15 in 24% of cases), compared to 4.5 for 80,000+ samples of diverse tumor types in the database. Of LCs assessed 0.3% were MSI-H, of which 30/31 were TMB-high; however, 24% of MSS-stable cases were also TMB-high. PD-L1 amplification and DNA repair pathway mutation (MLH1, MSH2, POLE) were found in 1.0% and 1.1% of LC cases analyzed, respectively. Tumors harboring known drivers (ALK, ROS1, EGFR, BRAF V600E, MET splice) had low TMB (median: 2.5, 3.6, 3.8, 3.8, 4.5), whereas tumors with KRAS mutation, non-V600E BRAF mutation, PD-L1 amplification, or DNA repair alterations were more likely to be TMB-high (median: 9.0, 10.8, 14.4, 21.6).

Conclusion:
High TMB may be a predictive biomarker of response to ICPIs. Several factors including lack of a known driver, MSI-H status, PD-L1 amplification, and DNA repair mutation correlated with high TMB (P<0.0001 for all cases). However, 95% of TMB-high cases assessed were MSS and lacked both PD-L1 amplification and DNA repair mutation, and thus would likely not be selected for immunotherapy by assessment of individual genomic alterations or MSI status alone. A validation cohort of NSCLC patients treated with anti-PD-1/PD-L1 therapies including analysis of clinical outcome, TMB, genomic profile, and available clinicopathologic characteristics will be presented. CGP of LC to simultaneously determine TMB, MSI status, PD-L1 amplification, and the presence of driver alterations may provide clinically useful predictors of response to ICPI and other targeted therapies using a single platform, but prospective clinical trials are needed to confirm these observations.

Background:
Currently the immune system is considered an important target of study within the therapeutic alternatives for many tumors that have developed resistance in lung cancer. Many molecules called checkpoints regulate antitumor immunity as PD-L1 it is expressed in tumour cells and is a biomarker for anti PD-L1/PD-1 therapy. PD-1 / PD-L1 is expressed on exhausted activated T cells. This signaling pathway is involved in tumor evasion of the immune system. It has recently been demonstrated that the blockade of PD-1 or its ligand PD-L1 and PD-L2, restore the antitumor immune response leading to a durable tumor regression. However, the expression of PD-1/PD-L1 in T cells from peripheral blood of patients with non-small cell lung cancer has not been widely studied.

Methods:
We investigated the expression of PD-1 and its ligands PD-L1 and PD-L2 on peripheral blood T cells subpopulations (CD3+ CD4+ / CD8+) of patients with non-small cell lung cancer. We included 50 NSCLC patients (stage IIIB and IV) naive to treatment and 10 healthy subjects. Immunophenotyping was performed using multiparametric flow cytometry. Analyzing its prognostic significance regarding outcome analysis as well as its potential biomarker.

Results:
Our results showed that the percentage of PD-1, PD-L1 and PD-L2 expression in peripheral blood cells in NSCLC patients was lower compared to healthy subjects [P<0.005] and the Mean Fluorescence Intensity (MFI) was higher in patients compared to the control group [P<0.001]; The expression of PD-1 in T-helper or CD4+ of NSCLC patients was significantly higher than in cells from control subjects [P<0.001]. Similarly, the expression of PD-1 in T cytotoxic cells or CD8+ patients was significantly higher than in controls [P<0.001]. In the clinical analysis, we found that a higher percentage of PD-1+ CD3+ cells was statistically associated with tobacco exposure [P=0.0160], and de MFI was associated with the non-adenocarcinoma histology [P=0.0001] additionally, the presence of 3 or more metastases was associated to a higher MFI of PD-1 on CD3+ CD8+ [P=0.0490]. In the overall survival (OS) analysis the percentage of CD3+/CD4+/PD-1+ ≤20.91 was associated with a higher median OS [P= 0.045].

Conclusion:
Several studies demonstrate the importance of infiltrating PD-1+ T cells within tumors; however these results showed that the PD-1/PD-L1/PDL-2 expression in peripheral blood cells could be used also as a potential biomarkers in NSCLC patients.

Background:
EGFR mutations define a distinct subset of NSCLC characterized by clinical benefit from tyrosine kinase inhibitors. The impact of genomic alterations that coexist with EGFR mutations is not fully understood. In addition, the responsiveness of EGFR mutant NSCLC to immune checkpoint blockade is not well defined.

Methods:
We queried our prospectively collected MD Anderson Lung Cancer Moon Shot GEMINI Database to identify EGFR mutant NSCLC patients. We analyzed the genomic landscape of these tumors derived from next generation sequencing, performed as part of routine clinical care, to comprehensively describe the concurrent genomic aberrations in EGFR mutant NSCLC and their impact on clinical outcomes. We used log rank and Fisher’s exact tests to identify associations between co-concurrent mutations and clinical outcomes.

Results:
1958 non-squamous NSCLC patients were identified in the GEMINI database. The frequency of EGFR mutations was 14.1% (n=276). Among EGFR mutant patients, 188 underwent targeted next generation sequencing of a minimum of 46 cancer related genes. The majority of EGFR mutant patients (77.6%, n=146) had at least one coexisting mutation. The most frequent co-mutations identified were TP53 (47%, n=88), CTNNB1 (7.5%, n= 14) and PIK3CA (6.5%, n=12). ALK and ROS1 translocations were found to coexist with EGFR mutations in one patient each. Of patients treated with a first or second generation TKI, concurrent TP53 mutations were associated with a shorter progression free survival (HR= 1.81, P= 0.039). Eight patients with EGFR/CTNNB1 co-mutations developed acquired TKI resistance with T790M secondary mutation being the resistance mechanism in six (75%) of them suggesting that coexisting mutation can dictate emerging resistance mechanisms. Twenty patients were treated with anti PD1/PD-L1 agents (nivolumab n= 18, pembrolizumab n=2). Only two (10%) patients achieved confirmed radiological response, one lasting for 6 months and the second ongoing at 6 months. Both patients were never smokers, one with EGFR exon 20 insertion and no concurrent mutations, and the other with EGFR exon 19 deletion and TP53 mutation. Sixteen patients developed confirmed progressive disease. Finally, one patient with 17 pack-year smoking history, EGFR G719/S768I double mutation and concurrent PIK3CA mutation achieved stable disease lasting for four months. The median progression free survival for the cohort treated with immunotherapy was 2 months (range: 1-not reached).

Conclusion:
Concurrent genomic aberrations may predict response duration to TKIs and may be associated with particular emerging resistance mechanisms to TKIs in EGFR mutant NSCLC. Immunotherapy results in durable clinical benefit in a subset of EGFR mutant NSCLC patients.

Abstract not provided

Background:
The KEYNOTE-010 (KN010) clinical trial, a multi-center, worldwide, randomized Phase II/III trial of pembrolizumab 2m/kg every 3 weeks and docetaxel 75mg/m2 every 3 weeks in patients with previously treated advanced NSCLC with PD-L1 positive tumors showed a significant overall survival (OS) advantage for patients receiving pembrolizumab. We examined the improvement in prognoses for patients who elect to learn their PD-L1 biomarker results using extrapolative survival modeling.

Methods:
Partitioned survival models to project long-term outcomes were developed using data from patients enrolled in KN010, with treated patients in the pembrolizumab 2m/kg and docetaxel 75mg/m2 arms included in these analyses. As OS for docetaxel patients is not dependent on PD-L1 status, KN010 results were assumed to represent docetaxel efficacy in all patients irrespective of PD-L1 status.The model projected expected lifetime using Kaplan Meier estimates of PFS and OS from the trial with extrapolation based on parametric functions and long term registry data.

Results:
Results directly from KN010 showed for patients with TPS≥50%, median survival to be 8.2 months (6.4, 10.7) and 14.9 months (10.4, NA) for docetaxel and pembrolizumab, respectively (HR= 0.54 (0.38, 0.77)). Model-based projections show that should all patients be treated with docetaxel, expected mean lifetime is 1.0 years. For patients receiving a PD-L1 biomarker test per KN010 28.49% will be identified as PD-L1 strong positive (TPS≥50%). PD-L1 (TPS ≥50%) predicts a life expectancy with biomarker directed pembrolizumab of 2.25 years on average.

Conclusion:
Use of PD-L1 biomarker identification can significantly improve OS prognoses for patients considering pembrolizumab and docetaxel with advanced NSCLC based on both clinical trial results and model-based projections from KN010.

Background:
Nivolumab is the first checkpoint inhibitor approved for the treatment of Sq-NSCLC to show a survival benefit vs the standard of care docetaxel in the randomised, phase III, CheckMate 017 study. In the nivolumab development program, a greater clinical benefit was shown in current and former smokers than in never smokers. Nevertheless, no data are available in this respect from a real world setting. For this reason, we decided to use the data collected in the EAP in order to assess the effectiveness and tolerability of nivolumab treatment in the never smoker patient population.

Methods:
Nivolumab was provided upon physician request for patients aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events using Common Terminology Criteria for Adverse Events.

Results:
Of 372 patients with Sq-NSCLC participating in the EAP in Italy, 38 (10.2%) were never smokers, a proportion very similar to the one observed in Checkmate 017 (10%). With a median number of doses of 8 (range, 1–22) and a median follow-up of 5.6 months, the disease control rate in this group was 50%, including 9 patients with a partial response and 10 with stable disease. Eight patients were treated beyond RECIST-defined progression, with 4 of them achieving disease control. As of April 2016, median progression-free survival and overall survival were 3.5 months and not reached, respectively. 17 patients (44.7%) discontinued treatment for any reason except toxicity and 5 (13.1%) discontinued due to AE.

Conclusion:
These preliminary results, although obtained from a small sample size, suggest that nivolumab is effective and well tolerated in a never smoker group of patients with advanced Sq-NCLCS in the real life and warrant further investigation in this area.

Background:
Randomized phase III trials have shown that the PD-1 blocking monoclonal antibody Nivolumab is effective in advanced NSCLC. Nivolumab is registered by the FDA and EMA for treatment of NSCLC. However, approval in The Netherlands was put on hold because of Nivolumab's high price per quality adjusted life year (QALY). From August 2015, Nivolumab was provided through a compassionate use program. Here we present our experience in treating NSCLC patients with Nivolumab in real life.

Methods:
Efficacy and safety of Nivolumab was assessed in patients with advanced NSCLC, previously treated with at least one line of platinum-based chemotherapy and an ECOG-PS of ≤2. Nivolumab was administered 2-weekly at a dose of 3 mg/kg intravenously. Response evaluation took place according to RECIST 1.1 at 12 and 24 weeks after start of treatment.

Results:
In the 10-month period in a single center 189 patients started treatment with Nivolumab, with a mean follow up time of 106 days after start of treatment. Mean age was 62 years (range 29–83), 57% male, 18,5% never smoked, 68% had adenocarcinoma, 20% had squamous histology and 12% were other, mixed or unspecified types. Figure 1 Twenty-four percent of patients experience immunotherapy related toxicity, most toxicities were short-term or easily manageable. No grade 5 toxicities, one grade 4 hepatitis and one grade 3 hypophysitis were observed. Hypothyroidism was most frequently observed (gr.1-2; 9,5%), followed by skin-reactions (gr.1-3; 3,8%) and colitis (gr.1-2; 3,2%). Other immune related toxicities were hepatitis (gr.1-4; 2,5%), infusion reactions (gr.1; 2,5%), pneumonitis (gr.2; 1,9%), hyperthyroidism (gr.1; 1,3%), arthritis (gr.2; 0,6%), hypophysitis (gr.3; 0,6%) and diabetes mellitus type 1 (gr.3, 0,6%).



Conclusion:
Although follow up is short and response data not yet mature, real-life efficacy and safety data from Nivolumab are comparable to phase III trial data.

Abstract not provided

Background:
Immuno-oncology (IO) therapies offer the possibility of long-term survival to metastatic cancer patients. Prior analyses have shown that lung cancer reduces life expectancy by an average of 11.8 years (Burnet NG, et al. Br J Cancer. 2005;92:241‒245.). We aimed to investigate the impact of IO therapies on life extension of patients with non-small cell lung cancer (NSCLC).

Methods:
We used The Health Economics Medical Innovation Simulation (THEMIS) alongside available clinical trial data to estimate the anticipated increase in NSCLC patient survival post-diagnosis resulting from the introduction of IO therapy. THEMIS is an established microsimulation with a 50-year time horizon that tracks a representative sample of patients aged ≥51 years to project longevity. These outcomes were estimated for metastatic NSCLC patients under a pre-IO scenario and compared to a post-IO scenario where IO is available for either first- or second-line treatment. Patients were classified as either heavy, medium, or light responders, corresponding to reductions in mortality hazards of 96.5%, 64.4%, and 0%, respectively, based on extrapolations of clinical trial results for nivolumab (see table). Health state transitions probabilities and medical expenditures were estimated from nationally representative datasets. Mortality and disease stage were estimated using the Surveillance and Epidemiology End Results (SEER) database.

Results:
In the pre-IO simulation, metastatic NSCLC patients lose 11.3 years of life (comparable with the published 11.8 years). The results from the post-IO scenarios are shown in the table. For comparison, SEER data suggest that survival in metastatic NSCLC patients has only increased by 0.3 years since 1998.

Population	Heavy Responder Prevalence	Medium Responder Prevalence	Heavy Responder Hazard Reduction	Medium Responder Hazard Reduction	Light Responder Hazard Reduction	Additional Life Years
Second-line monotherapy, All patients	20%	30%	96.5%	64.4%	0%	2.1
First-line monotherapy, PD-L1 >1%	30%	40%	96.5%	64.4%	0%	3.25
First-line monotherapy, PD-L1 >50%	50%	40%	96.5%	64.4%	0%	4.72
First-line combination therapy, PD-L1 >1%	60%	30%	96.5%	64.4%	0%	4.22
First-line combination therapy, PD-L1 >50%	100%	0%	96.5%	N/A	N/A	7.06

Conclusion:
Current IO therapies represent a significant step towards extending life expectancy for metastatic NSCLC patients.

Background:
This study aimed to understand the impact on disease management costs beyond drug acquisition costs in the context of an economic evaluation of pembrolizumab compared with docetaxel in patients in patients with previously treated PD-L1 positive (TPS>=50%) advanced NSCLC. The analysis was conducted from a US third-party payer perspective.

Methods:
A partitioned-survival model was developed using data from patients from the KEYNOTE-010 (KN010) clinical trial. The model used KM estimates of PFS and OS from the trial for patients treated with pembrolizumab 2mg/kg and docetaxel 75kg/m[2] with extrapolation based on fitted parametric functions and long-term registry data. Costs of clinical management of advanced NSCLC along with drug acquisition/administration and adverse event management costs were included in the model. The base-case analysis used a time horizon of 20 years. Costs and health outcomes were discounted at a rate of 3% per year.

Results:
Base case results project for PD-L1 positive (TPS>=50%) patients treated with pembrolizumab a mean survival of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated. Weekly disease management costs observed in KN010 for the progression-free state were $866 and $1,298 for pembrolizumab and docetaxel, respectively. Weekly disease management costs for the progressive disease state were $1,938 based on a US healthcare claim database. Results projected total disease management costs to be $166K per patient treated with pembrolizumab compared with $93K for docetaxel because of extended progression-free and post-progression survival with pembrolizumab. Nearly half (45%) of total expected cost differences between pembrolizumab and docetaxel are due to the incremental disease management costs. Further analyses that exclude drug treatment costs show that the additional disease management costs associated with extended progression-free and overall survival exceed $50,000 per LY gained ($61,864).

Conclusion:
Pembrolizumab improves outcomes compared to docetaxel in PD-L1 positive (TPS>=50%) pre-treated advanced NSCLC patients in the US. The improved overall survival with pembrolizumab is accompanied by the economic reality of additional non-pembrolizumab costs that represent their own substantial economic burden.

Background:
Delivering high quality cancer care at an affordable cost is one of the main challenges for health care professionals and policy makers, especially in low- and middle-income countries. The objective of our study is to assess the economic impact of nivolumab and pembrolizumab with and without the use of PD-L1 as a biomarker in Brazil.

Methods:
We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and the second-line treatment with NIVO or PEMBRO versus docetaxel. The model used outcomes data from randomized clinical trials and drug acquisition costs were estimated using current prices in Brazil. Thereafter, we used Brazilian epidemiologic data to estimate the economic impact.

Results:
We included three RCTs (two with NIVO and one with PEMBRO). The estimated number of cases eligible for therapy with immune checkpoint inhibitors is 4,733. Treating all patients with NIVOLUMAB would cost US$ 173 million dollars each year, representing an increase of 21% in current Brazilian expenses for cancer drugs acquisition. Treating only patients with PD-L1 > 1% with NIVOLUMAB would cost 93 million dollars every year, leading to an increase of 11.3% in expenses for cancer drugs acquisition. However, with such selection, up to 46% of cases would not be treated and 315 years of life would be lost compared to treating all patients regardless of PD-L1 expression. The cost of each year-of-life saved was improved by PD-L1 selection (from US$ 196,000 to US$ 164,000). Table 1 summarizes our findings for five different scenarios of treatment. The results were similar with NIVOLUMAB and PEMBROLIZUMAB.

SCENARIO	QALY GAIN	ICER (US$)	LIFE-YEARS SAVED	YEARS OF LIFE NOT SAVED	% NOT TREATED	TOTAL COST (US$)	IMPACT ON TOTAL CANCER DRUG EXPENDITURE	COST/LYS (US$)
NIVO ALL COMERS	0.148	129 K	885	0	0%	173 Million	21.1%	196 K
NIVO PD-L1 > 1%	0.201	108 K	570	315	46%	93	11.3%	164 K
PEMBRO PD-L1 > 1%	0.138	137 K	666	NA	34%	100	12.1%	150 K
NIVO ALL SQ/ > 1% NSQ	0.216	99 K	738	147	35%	116	14.0%	157 K
PEMBRO PD-L1 > 50%	0.164	116 K	285	NA	72%	43	5.2%	151 K

Conclusion:
The use of PD-L1 expression as a biomarker for treatment with immune checkpoint inhibitors decreases the overall economic impact and the cost per life-year saved. Further study and societal discussion is needed in order to find the optimal strategy for patient selection.

Abstract not provided

Background:
The advanced practice nurse in lung cancer (APNLC) has shown to play a key role in meeting the complex supportive care needs of patients with lung cancer. Nurses working in novel advanced practice nursing (APN) roles encounter a range of barriers to effective practice particularly in countries without an existing regulation of these novel roles. Being accepted by patients and healthcare professionals (HCPs) is fundamental for successful role implementation. The University Hospital of Lausanne (CHUV) was the first comprehensive cancer center in Switzerland to integrate an APNLC into the specialized multidisciplinary team (MDT) of the thoracic cancer center. To overcome barriers to implementing the APNLC role and promote its long-term viability, we aimed to explore the acceptability of this novel APNLC role from the perspective of the MDT and the patients cared for by the APNLC.

Methods:
This qualitative study was part of a larger implementation study (ClinicalTrials.gov, Number: NCT02362204). During summer 2015, we conducted focus groups and semi-structured interviews in the thoracic cancer center of CHUV. Participants were purposefully sampled and included patients with lung cancer (n=4) and HCPs from the MDT [physicians (n=6), nurses (n=5)], a social worker and the APNLC. Semi-structured individual interviews were conducted to examine the perspectives of patients and the APNLC alike. Focus groups were employed to gather perspectives from the MDT. Data were analyzed using thematic content analysis.

Results:
Three main themes emerged describing the acceptability of the APNLC: “role identification”, “role-specific contribution” and “flexible service provision”. Physicians and patients identified the specific APNLC role within the MDT. In particular, they valued specific contributions to continuity of care, psychosocial support and self-management of symptoms. Nurses perceived the APNLC role as overlapping with the traditional oncology nurse role. They were concerned about losing part of their traditional role. Flexibility in service provision was seen as strength of the APNLC role yet also posed organizational challenges related to the work-load.

Conclusion:
The new APNLC role appears to be well-accepted by patients and physicians. Barriers identified during the implementation of the APNLC role were primarily related to intra-professional and organizational challenges. The intra-professional role tension could challenge effective role implementation. To maximize the acceptability of a new APNLC role - particularly in countries that are in an early stage of APN role development - we recommend formalizing nursing role expectations, providing appropriate support/resources and promoting a national plan for APN accreditation and certification.

Background:
Immunotherapy is rapidly becoming recognized as the fourth pillar of treatment for lung cancer. As an academic center of excellence, our staff have developed expertise with immune-oncology (I-O) agents though clinical trials. Currently two agents (Nivolumab and Pembrolizumab) have been FDA-approved for the treatment of lung cancer. Variability existed in patient assessment, patient education and staff education regarding how to identify and manage immune-related adverse events (IrAEs).

Methods:
Initial evaluation consisted of an online staff survey and interviews to assess the educational materials available for instruction of both patients and staff. A review of existing educational materials was conducted to determine the breadth of information available as well as knowledge gaps. The evaluation revealed a lack of standardization, with inconsistency in the educational messages being delivered. A focused working group including CNS, APRNs, Pharmacists and RNs from the academic hub and broader community care center network was convened with the goal of developing educational platforms for nursing staff as well as patients. Bringing stakeholders together was felt to be important to increase buy-in across the spectrum of care locations, as well as to ensure that the program was effective and appropriate for all sites. Program components included the following: -Education for staff to better identify and manage IrAEs -Development of an electronic nursing flow-sheet to standardize patient assessment and document IrAEs in the lung cancer population. -Automatic notification through the EMR to alert staff in non-oncology settings regarding I-O patients. -Development of a forum for patient education to better understand I-O therapy and how to identify and manage IrAEs. - Development of lung cancer specific telephone triage guidelines

Results:
The outcomes of implementing the I-O program include increased patient participation in educational forums and improved patient satisfaction metrics. Incorporation of the I-O assessment flow-sheet and telephone triage guidelines will improve staff competency, as well as standardize documentation and monitoring of IrAEs. These metrics will allow for more accurate tracking of IrAes throughout the course of treatment.

Conclusion:
The I-O Integrated Education and Assessment Program standardizes practice across all oncology care delivery sites within our network. This program allows patients to receive the highest level of care at convenient regional locations closer to home, with the goal of maintaining patient safety while maximizing the benefit they may receive from I-O therapies. An integrated

Background:
A diagnosis of advanced lung cancer inevitably results in deterioration in both health and functional status. This threatens a person’s independence and dignity and can be a burden to their family and carers. The lung cancer nursing team at Oxford identified a lack of timely therapy provision for their patient group and sought to improve this, concluding that having an occupational therapist (OT) in the team would significantly expand/diversify the service that could be offered to patients. Lung cancer therapy goals were identified as a) working with patients and carers to anticipate functional need rather than waiting for a crisis to occur b) providing a rapid, flexible and responsive service to those with existing needs and c) working in a keyworker role outside of traditional therapy expertise supporting patients at diagnosis, making treatment decisions and providing information .

Methods:
Funding was obtained from Macmillan Cancer Support for a three year project looking at delivering a new model of care. An Advanced Therapist Practitioner (ATP) with an OT background was recruited and embedded into the nursing team full time. Referrals were received from all members of the lung cancer MDT, the inpatient team, primary and palliative care. Interventions included home assessment, outpatient clinic review, breathlessness and anxiety management, provision of aids, support, education and advice.

Results:
Data was gathered from a one year period when there were 305 new lung cancer diagnoses. 165 (54%) patients had identified therapy needs. A further 40 (13%) patients were seen by the ATP as part of her generic keyworker role. 205 referrals resulted in a total of 1005 interventions averaging 5 per person. Interventions were allocated to three levels ranging from simple telephone calls and liaison to complex case management. Average time from referral to first contact with the patient was half a day. The value of the role was measured in three ways: User Feedback Event, Satisfaction Questionnaire and a Stakeholder Questionnaire. Outcomes were overwhelmingly positive.

Conclusion:
Lung cancer patients have high functional needs. An ATP can become an integral part of traditional specialist nursing teams, is able to work in a keyworker capacity and is well accepted and used by the lung cancer MDT. The ATP role provides a strong bridge between primary and secondary care environments and preserves independence and dignity for longer. Evidence from users and stakeholders demonstrated high levels of satisfaction and quality of care.

Abstract not provided

Background:
The United Kingdom National Lung Cancer Forum for Nurses Workshop 2015 produced guidance to support Lung Cancer nurse Specialists in developing and evaluating nurse-led clinics. Nurse-led clinics have been in existence for years with little guidance on structure and evaluation. They are safe and effective. Nurses provide individual care that makes a difference to patient outcomes. There is vast evidence available for nurse-led services but significantly less on lung cancer specific services despite a growing body of evidence to support this.

Methods:
A literature search was performed. This included developing a lung cancer nurse-led clinic, evaluation, audit tool and measurement. The initial search found limited number of relevant documents. Therefore the search was widened to include developing general nurse-led services. The NLCFN members were surveyed to evaluate current nurse-led clinics. The questionnaire comprised of eighteen questions incorporating all aspects of nurse-led follow up.

Results:
60% responded, suggesting a high interest in the area. Over half of the respondents ran nurse-led clinics. These included telephone, results, post-surgery, Health & Well being, TKI and breathlessness clinic. However 67% had not evaluated or audited these, 74% didn’t have patient information leaflets and 96% had access to medical cover. The seven most important steps in developing a lung cancer nurse-led clinic are: Aims and Objectives, Planning and Consultation, Multidisciplinary Support, Infrastructure, promoting the nurse-led service, Professional Development and Audit and Evaluation. These formed the basis of this framework.

Conclusion:
NICE (2011), suggests that patients should be offered a “follow-up led by a LCNS” . However, nurse-led clinics are challenging and there are many practical and emotional hurdles to be overcome. This framework supports LCNS’s in developing and evaluating nurse-led clinics . It gives clear guidance to be considered when developing and new service as well as advising on audit/evaluation tools and developing patient information leaflets.

Background:
In the United Kingdom thoracic cancer is mainly diagnosed in an older population, who generally have significant co-morbidities, and advanced stage disease. Due to this, they experiences high levels of disease burden, both physical and psychological, impacting on individuals’ functional independence and quality of life (QoL). The national governing bodies, such as NICE and LCA, recommend that all patients should have access to an Holistic Needs Assessment (HNA) and rehabilitation services. At Guy's And St Thomas' NHS Foundation Trust (GSTFT) we have developed a multi-disciplinary team (MDT), consisting of Dietetics, Occupational Therapy (OT) and Physiotherapy (PT), who are present within the outpatient thoracic oncology clinics and aim to address the rehabilitation and supportive care needs of all patients.

Methods:
All new thoracic oncology patients attending outpatient consultant lead clinics at GSTFT were offered an HNA, in order to identify their individual concerns/needs. The assessments are completed by the MDT and individual intervention plans created. Over a three-month period, January to March 2015, data was collected on patient's diagnosis, treatment offered, treatment intent, symptom concerns, QoL indicators, onward MDT referrals and mortality.

Results:
82 patients completed the assessments, of these 85% reported unmet needs/concerns. The main tumour types seen were Adenocarcinoma, Squamous cell carcinoma, mesothelioma and small cell lung cancer. Of those reporting symptoms the most common were; breathlessness (55%), fatigue (52%), reduced appetite (43%), weight loss (41%), pain (37%), emotions/mood (33%). sleep concerns (33%), and reduced mobility (32%). 69 patients had onward referrals to supportive care services. The most common referrals were; OT (65%), PT (60%), Dietitian (43%), and patient information (38%). 66% of patients were provided with on the spot MDT intervention.

Conclusion:
Providing thoracic oncology patients access to an MDT service on their initial oncology visit, has enabled early identification of the key symptoms this patient group experience, as well as the need for allied health services. This has supported the role of early rehabilitation as being integral to improving patient's level of symptom burden and QoL. Moving forward it would be beneficial to do a comparative study of the symptoms and intervention needs of this patient group over a longitudinal analysis, with the aim of showing the impact of early rehabilitation on patient's QoL, survivorship, and life expectancy.

Background:
Patients with lung cancer (LC) report lower quality of life (QoL) and higher levels of psychological distress compared to other cancer populations (Hewitt et al, 2013). Lung cancer stigma (LCS) may in part explain these findings. Evidence from studies in the Unites States has shown associations between LCS and lower QoL, higher symptom burden and higher levels of anxiety and depression (Cataldo et al, 2013). Whether these associations exist in people diagnosed with LC in the United Kingdom is unknown. Therefore this study explored the prevalence of LCS and its relationship with patient outcomes as well as QoL in a Scottish population.

Methods:
This study was a cross-sectional study. Patients (n=201) diagnosed with LC were recruited by health care professionals at follow-up clinics at four hospitals in Scotland. Participants completed questionnaires to collect demographic data and assess perceived LCS, QoL, symptom severity and level of depression. Clinical data was collected by casenote review. Bivariate correlations were performed to investigate the relationships between stigma, demographics, and patient outcomes. Multiple regression further explored the individual contributions of LCS on symptom burden and quality of life.

Results:
Participants had a mean age of 69 years (range 41-89 years), 46.8% were males, 92.0% were ever smokers, 17.9% current smokers. The mean LCS score was 53.1 (SD=14.1, range 31-124,). There were significant correlations between higher LCS and age (r= -0.28, p<0.001), being a current smoker (r= 0.17, p<0.05), deprivation index (r=0.15, p<0.05) depression (r=0.40, p<0.001), symptom burden (r=2.60, p<0.001), and QoL (r= - 0.52, p<0.001). Multiple regression revealed an overall model that explained 30.6% of the total variance of stigma (F=14.82, p<0.001). Perceived stigma also accounted for significant unique variance in QoL (4.3%, p<0.001) and depression (3.6%, p<0.001) above and beyond that accounted for by relevant variables. No contribution of stigma on symptom burden was found.

Conclusion:
Stigma was correlated with depression, and QoL. Therefore, it is expected that depression and stigma share some of the explanation of variance of QoL. Nevertheless, stigma was found to have a unique contribution on QoL, and on depression. With this in mind, management of patients with LC could determine the patients’ experience of stigma to tailor treatment plans to improve QoL and psychosocial outcomes. Being younger was correlated with higher LCS. This might reflect changed attitudes toward smoking due to changed marketing strategies in the 1960s.

Abstract not provided

Background:
The objective of this study is to confirm limited resection efficacy as radical surgery in patients with minimally invasive lung cancer as indicated by high-resolution (HR) computed tomography (CT), and to confirm intraoperative cytology as a negative margin indicator and reliable margin non-recurrence predictor.

Methods:
Enrollment required patients with a tumor ≤ 2 cm in diameter, diagnosed or suspected as a clinical T1N0M0 carcinoma in the lung periphery based on a CT scan. They had to have a HRCT scan indicating a sub-solid nodule with tumor disappearance ratio; TDR ≥ 0.5. (TDR = 1- DM/DL; DM: maximum tumor diameter on mediastinal settings, DL: maximum tumor diameter on lung settings). Patients unfit for lobectomy and systematic lymph node dissection were excluded. We performed a wedge or segmental resection. The used stapling cartridges were washed with saline, which was cytologically evaluated. If cytology was cancer positive, additional margin was resected, and cytologic examination repeated. If the second exam was positive, a routine lobectomy and systematic lymph node dissection was performed. We aimed at enrolling 100 patients. The primary endpoint is 10-year local recurrence free survival rate.

Results:
This prospective study started in November 2003, and 101 patients were enrolled in 6 years. Of them, 99 were eligible for analysis. The mean age was 62 years (range: 30-75), and 60 were women. There were 11 Noguchi type A tumors, 54 type B tumors, 26 type C tumors, one type D tumor, one malignant lymphoma, 3 hyperplastic lesions, and 3 inflammatory fibroses. None of the 93 malignant nodules showed any vessel invasion. Although no positive cytology results were obtained, pathologically positive margin was reported after surgery in one type C patient. He later underwent a routine lobectomy and systematic lymph node dissection. There was no clear correlation between tumor size, TDR, and Noguchi subtype. No mortality occurred, but one patient developed postoperative pneumothorax and pneumonia, and another hemorrhagic gastric ulcer. With a median follow-up period of 105 months (range: 72−129) as of June 2016, there have been no recurrences, but one patient died for unspecified cause.

Conclusion:
We have repeatedly warned that delayed cut-end recurrence is possible following limited resection even for small sub-solid lung cancers. So far, however, HRCT scans appear to predict non- or minimally invasive sub-solid lung cancers with high reliability, warranting limited resection as curative surgery in this cohort. Intraoperative cytology reliably indicated negative margins and seems to predict freedom from local recurrence.

Background:
Lobectomy remains the standard treatment for early-stage non-small cell lung cancer (NSCLC).In practice, however, sublobar resection has been selectively offered for patients with clinical Stage IA NSCLC as curative treatment. To seek optimal surgical procedure for early stage lung cancer, we carried out retrospective analyses of 2122 patients who had undergone limited resection for c-T1N0M0 NSCLC from 26 institutions of Japanese association for chest surgery.

Methods:
A total of 1963 patients with lobectomy tolerance were eligible for survival analysis. We retrospectively categorized patients of these nodules on numbers of criteria for CT findings; scores were added according to the dominance of ground glass appearance (GGA); >75% = 0, <75% =1, and size of tumor; T1a =0, T1b =1. Statistical analyses were carried out using propensity-matching and Kaplan-Myer with log-rank testing.

Results:
We analyzed 1:1 matched 731 patients for segmentectomy and wedge resection with propensity matching.The overall survival (OS) for score 0 group was 90.2% in segmentectomy (n=419) and 94.7% in wedge resection (n=451) (p=0.0351). The disease free survival (DFS) for score 0 group was 90.2% in segmentectomy and 92.7% in wedge resection (p=0.0645). The OS for score 1 group was 93.6% in segmentectomy (n=278) and 80.4% in wedge resection (n=246)(P<0.001)(Fig. 1). The DFS for score 1 group is 94.1% in segmentectomy and 75.3% in wedge resection (P<0.001). The OS for scores 2 was 79.1% in segmentectomy (n=34) and 69.2% in wedge resection (n=34) (p=0.109). The DFS for score 2 group was 87.0% in segmentectomy and 58.1% in wedge resection (p=0.581). Figure 1



Conclusion:
This study showed that GGA dominant T1a may be treated by wedge resection where possible. The consolidation dominant T1b did not benefit from sublobar resection. In patients with GGA dominant T1b or consolidation dominant T1a, anatomical segmentectomy with curative intension may provide better prognosis.

Background:
The prognosis after standard lobectomy for non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD) is poor. This study aimed to compare the prognosis after lobectomy and sublobar resection for early NSCLC with ILD.

Methods:
Among 794 consecutive patients with clinical stage I NSCLC who underwent complete resection, 107 patients with ILD on high-resolution computed tomography (HRCT), which was defined according to the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association classification, were identified.

Results:
Overall survival (OS) was significantly worse for patients with possible usual interstitial pneumonia (UIP) or UIP pattern than those with inconsistent with UIP pattern (3-year OS, 64.5% vs. 82.1%, respectively; P = 0.031). No significant difference existed in OS between lobectomy and sublobar resection for all patients with ILD (3-year OS, 67.1% vs. 81.9%, respectively; P = 0.14). Although in patients with inconsistent with UIP pattern, OS was similar between lobectomy and sublobar resection groups (3-year OS, 81.1% vs. 83.6%, respectively; P = 0.87), OS was better for patients who underwent sublobar resection than lobectomy in patients with possible UIP or UIP patterns (3-year OS, 81.0% vs. 50.5%, respectively; P = 0.069). Multivariate Cox analysis demonstrated that preoperative diffusing capacity of the lung for carbon monoxide (P = 0.018), not the surgical procedure (P = 0.14), was an independent prognostic factor for OS.

Conclusion:
Sublobar resection can be an alternative choice for clinical stage I NSCLC with ILD especially for UIP or possible UIP patterns on HRCT.

Abstract not provided

Background:
The identification of an accurate segment is essential for successful anatomic pulmonary segmentectomy. We have previously developed a new fluorescence technique using a PDD endoscope system[TM] and vitamin B2 for identification of pulmonary segments in animal experiments. In this study, we applied this technique clinically to examine the efficacy and safety in anatomical pulmonary segmentectomy and sub-segmentectomy for pulmonary malignancies.

Methods:
Our technique requires two key instruments, a PDD endoscope system[TM](KARL STORZ GmbH and Co., Tuttlingen, Germany) as a fluorescence sensing device and vitamin B2 solution as a fluorescent substance. 17 patients with small lung nodules were enrolled in this study. Regarding our surgical technique, after identification of the target segmental or sub-segmental bronchus, vitaminB2 solution is injected via the bronchus. The target segment is identified as a fluorescent segment with the PDD endoscope system[TM]. The identified segment is resected with an electric cautery, stapling devices, or combination of them. In case patient’s lung has severe abnormal change such as emphysema or fibrosis, another technique is indicated. After ligation of the target segmental or sub-segmental artery, vitaminB2 solution is systemically administrated with intravenous injection. The target segment is identified as a defect of fluorescence with the PDD endoscope system[TM]. Following outcomes were collected; success rate of identifying the pulmonary segments, pathological evaluation of dissection margin, duration of chest drainage, and perioperative complications.

Results:
A total of 18 procedures were performed using this technique. Performed segmentectomy or sub-segmentectomy were as follows; Right S1, S2, S3, S2a+3b, S6, S9, Left S1+2, S3, S4+5, S6, S8a+9b, S9+10. Resected nodules were 14 primary lung cancers, 1 MALT-lymphoma, 1 metastatic lung cancer, and 2 benign lung nodules. Histology of primary lung cancer was adenocarcinoma in all 14 cases. Pathological stage of lung cancer was 12 stageIA (pT1a; 10, pT1b; 2), 1 stageIIA (pT1aN1), and 1 stageIIIA (pT1aN2). The success rate of identifying pulmonary segments was 100%. Dissection of segmental border was performed with only electric cautery in 12 procedures, and with both of electric cautery and stapling device in 6 procedures. In all cases, no cancer cells were found on the resection margin pathologically. Mean drainage time was 1.7 days (1-4 days). Regarding perioperative complications, veno-vagal reflex was occurred after systemic injection of vitaminB2 in one case, and 1 delayed pneumothorax was found in one case.

Conclusion:
Our novel fluorescence technique involving a PDD endoscope system[TM] and vitaminB2 allowed performing accurate and safe pulmonary segmentectomy and sub-segmentectomy.

Background:
Although the confirmation of an appropriate resection margin from the tumor is crucial for reducing the risk of local recurrence after lung segmentectomy for pulmonary malignancies, there has been no method of measurement. We established a novel approach for performing segmentectomy by using an infrared thoracoscopy with transbronchial instillation of indocianine green (ICG), and improved this method by adding an advanced computer technology via lung volume analyzer for obtaining an appropriate resection margin.

Methods:
Preoperatively, each patient underwent multislice enhanced computed tomography (CT) using 320-slice scanners for pulmonary angiography and virtual bronchoscopy, and to create several virtual segmentectomies by using Volume Analyzer Synapse VINCENT (Fujifilm co., Tokyo, Japan). We measured the shortest distance from the tumor to the resection margin in each simulated segmentectomy and selected the most appropriate area of sublobar resection based on the adequate resection margin of approximately 2 cm from the tumor. We prospectively performed segmentectomy in 17 patients and compared between simulated distance and actual distance measured from the specimen.

Results:
The average number of created patterns of virtual segmentectomy in each case was 4.1 ± 1.0. The mean distance of resection margin in selected virtual segmentectomy was 19.3 ± 9.7 mm. On the other hand, actual shortest distance in resected specimen was 25.4 ± 8.1 mm, which was significantly longer than simulated distance (p=0.027). There was no tumor recurrence in all patients.

Conclusion:
Lung volume analyzer was an excellent tool for selecting an ideal area of sublobar resection with an appropriate resection margin.

Background:
The standard surgical treatment of stage I non-small cell lung cancer is anatomical lobectomy. However, in some cases, small peripheral lung cancer (≤2cm) is treated by sublobar resection. The purpose of this study was to define the necessity of completion lobectomy when the tumor was revealed as non-small cell lung cancer with pleural invasion or lymphovascular invasion after sublobar resection.

Methods:
We retrospectively reviewed 271 consecutive patients who underwent curative resection for stage I non–small cell lung cancer of 2 cm or less. We analyzed clinicopathological findings and survival between two groups with either invasion-positive tumor (tumor with visceral pleural invasion or lymphovascular invasion) or invasion-negative tumor (tumor without visceral pleural invasion and lymphovascular invasion): sublobar resection group and lobectomy group.

Results:
Except for age and pulmonary function, there were no differences in clinocopathological characteristics between sublobar resection group and lobectomy group with invasion-positive tumor or invasion-negative tumor. There was no difference in the 5-year recurrence-free survival rate between two groups in the invasion-positive tumor and invasion-negative tumor (78.9% vs 79.8%; p=0.928, 80.2% vs 85.4%; p=0.505). In the multivariate analysis, only number of dissected lymph nodes was a significant recurrence-related factor of stage I invasive-positive non-small cell lung cancer (hazard ratio 0.914, 95% confidence interval 0.845-0.988, p=0.023). Sublobar resection was not a risk factor for recurrence.

Conclusion:
The survival between sublobar resection group and lobectomy group in small (≤2cm) non-small cell lung cancer with visceral pleural invasion or lymphovascular invasion were not different. Completion lobectomy is not necessary in small lung cancer after sublobar resection whether the tumor has visceral pleural invasion or lymphovascular invasion.

Abstract not provided

Background:
The recent emergence of multiple new targeted therapies and immunotherapy drugs has significantly increased options in the systemic treatment of lung cancer (LC). While great news for patients, in the current environment of scarce health care resources, government agencies deliberating on public funding of cancer drugs struggle with ensuring sustainability of the public health system due to increasingly expensive drug costs. In Canada, the Pan-Canadian Oncology Drug Review (pCODR), a program of the Canadian Agency for Drugs and Technologies in Health (CADTH), provides recommendations that informs public funding decisions for cancer drugs. pCODR’s recommendations apply an evidence-based deliberative framework which considers the drugs clinical benefit, patient-based values, cost-effectiveness and adoption feasibility. As part of the pCODR review, patient input is integrated into the clinical and economic reports and recommendations. Patient groups, such as Lung Cancer Canada (LCC), can play a pivotal role by synthesizing the evidence gathered from patients and caregivers to inform the pCODR process.

Methods:
Both quantitative and qualitative techniques were used to gather data for LCC’s pCODR submissions. A national survey – the Faces of Lung Cancer (FOLC) - illustrated the perceptions and general unmet needs of those living with LC. Focus groups, one-on-one interviews and audits of patient discussion boards gathered the insights of patients and caregivers with experience on the drug under consideration. Patients were identified through LCC’s Medical Advisory Committee and their networks, clinical trial investigators, outreach to other patient groups and scans of LC patient/caregiver discussion boards.

Results:
Since 2014, LCC has made five pCODR submissions. 91 patients and 72 caregivers participated in the FOLC survey. The insights of an additional 62 patients and 38 caregivers with experience on the drugs under consideration were gathered qualitatively. LCC’s submissions describe the emotional, practical and logistical challenges of living with LC, and illustrate the “life impact” of the drug under consideration. - factors not traditionally included in clinical trial design.

Conclusion:
pCODR’s deliberative process, partnered with LCC’s methodology, may be an effective model to aid public funding discussions of new cancer drugs. pCODR and the reviewers have found patient group submissions valuable in providing lived-experience insight, at times changing perspectives. LCC’s contribution has been strongly reflected in the funding guidance reports. To supplement its process, pCODR recently launched a pilot project to include clinician input in the review process. The impact of the pilot will be assessed as data becomes available.

Background:
Shared decision making (SDM) between the patient and their physicians is recognized as a desirable goal. When one treatment option is not clearly superior to another, PDAs can help present risks and benefits in a simple, visual format. Of the 600 plus validated PDAs, less than 60 of these are designed for cancer treatment decisions, and only 10 deal with lung cancer diagnosis or treatment (www.ohri.ca/decisionaid). A survey of lung cancer patients or their significant others/caregivers collected information regarding decision making experiences, and the perceived usefulness of PDAs.

Methods:
A survey (via SurveyMonkey) was sent to lung cancer patients/caregivers/significant others who had signed up for email communication from the Bonnie Addario Lung Cancer Foundation (ALCF), Global Resource for Advancing Cancer Education (GRACE), or the University of Colorado. The survey collected information regarding demographics, categorization of the difficult problem, and the sources of problems encountered during decision making. A PDA regarding prophylactic cranial irradiation (PCI) for limited small cell cancer was made available, and opinions were sought regarding the usefulness of this format.

Results:
190 responses were obtained (123 patients, 67 other). This was predominantly a well-educated, white, North American population, with advanced disease, with more women than men (75% vs 25%). 115 (61%) of respondents had faced a difficult decision, women more so than men. Decisions regarding systemic therapy were the most commonly perceived difficult decision (58%) and/or tests that were done/not done (34%). Sources of difficulty were identified as insufficient information (44%), or conflicting information or recommendations from their physicians (34%). The amount of information available was categorized as insufficient, just right, too much or difficult to know in 14%, 22%, 2%, 50%. Men were more likely to indicate that they had sufficient information, 39% vs 14%, p< 0.05. Most patients desired SDM, with only 9% expressing the desire to make the decision alone. However, 26% perceived that they had done so. Fortunately, only 8% of respondents expressed regret regarding their decision. Of 90 respondents who viewed the PCI PDA, 61% felt that this type of decision aid would have been helpful. There were no gender differences regarding opinions towards the PDA, the desire for SDM, or the perception that it had occurred.

Conclusion:
Lung cancer patients desire shared decision making. Improvements in this process are perceived as needed, possibly with PDAs.

Background:
The disparities in lung cancer treatment and outcomes among minorities are well documented.1 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 Bonnie J. Addario Lung Cancer Foundation (ALCF) 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 minority and 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.

Methods:
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.

Results:
The COE program serves thousands of patients each year with a significant representation of minorities and underserved populations. Baptist Memorial Health Care System is an example of a COE that has demonstrated implementation of the COE model by providing multi-disciplinary care to a diverse population. Among those reporting race at Baptist, minorities represent more than 30% of lung cancer patients. Memorial Health Care System is another COE that is reaching and serving a diverse patient population. The patient mix at Memorial is : 64% whites; 18% Hispanics; and 18% African American. At Memorial, approximately 10% of the patient population is uninsured. Further, Memorial molecularly tests all stage III/IV patients. Compared with community hospitals in the National Cancer Database the patient mix is about 84% white, 2.5% Hispanic and 11% African American with 3% uninsured.

Conclusion:
The ALCF COE program is demonstrating that underserved lung cancer patient populations can be reached and receive standard of care treatment. The patient-focused COE approach effectively removes barriers to quality care.

Abstract not provided

Background:
Socioeconomic disparities in survival of patients with lung cancer have been identified in many countries. The aim of this study was to examine determinants of late diagnosis of lung cancer in France.

Methods:
All patients with a first diagnosis of lung cancer in 2011 in the National hospitals databases were included. Information on gender, age, presence of metastasis at diagnosis and any significant chronic comorbidities (hypertension, diabetes mellitus, renal insufficiency, and other chronic lung diseases) was retrieved. Based on municipality of residence, patients were classified by population density, social deprivation, access to general practitioners and pulmonologists.

Results:
We identified 41,015 patients newly diagnosed for lung cancer in French hospitals. Mean age at diagnosis was 66.4 (±11.9) years and 72% patients were men. 53% (N=21,613) patients were metastatic at the time of diagnosis. This rate was higher for patients in public compared to private hospitals (56.1% vs 42.9%, p<0.0001) and in community compared to university hospitals (60.2% vs 49.6%, p<0.0001). Multivariate analysis found that metastases at the time of diagnosis were significantly associated with a younger age (55 years or less, OR: 1.22 [95%CI:1.16–1.29]; p<0.0001), a low access to pulmonologists (OR: 1.13 [95%CI:1.04–1.23]; p=0.004), a rural or semi-rural dwelling (OR: 1.07 [95%CI:1.02–1.13]; p=0.004) and deprived areas (OR: 1.06 [95%CI:1.01–1.11]; p=0.01). Of the 8,413 patients (20%) who were initially admitted through emergency room (ER) 68.1% had metastatic tumors. Multivariate analysis showed significantly higher rate of admission through ER at diagnosis in patients from most deprived areas (OR: 1.44 [95%CI:1.37–1.52]; p0.0001), rural or semi-rural (OR: 1.25 [95%CI:1.19–1.32]; p<0.0001), with a low access to pulmonologists and general practitioners (OR: 1.24 [95%CI:1.17–1.30]; p<0.0001 and 1.15 [95%CI:1.08–1.23]; p<0.0001, respectively). Gender (male) and presence of comorbidities were also significant determinants of metastatic disease and admission through ER at diagnosis.

Conclusion:
A majority of French patients with lung cancer were initially metastatic at the time of diagnosis and 1 out of 5 were diagnosed following admission through ER. Residential socioeconomic indicators and access to general practitioners and pulmonologists were significantly associated with these indicators of poor outcome.

Background:
In this era of precision medicine, biomarker testing of cancer tissue is sometimes necessary to match the right patient to the right treatment. A patient might need multiple biopsies if there is recurrence of lung cancer, or to determine eligibility for a new drug or participation in a clinical trial. Anecdotal evidence suggests that physicians are unwilling to recommend additional biopsies because they assume that the patients are likely to refuse.

Methods:
To understand this patient-physician communications gap, we asked 340 lung cancer survivors through an online survey about their willingness to undergo additional biopsies. The survey was fielded through various social media platforms as well as through an independent research panel.

Results:
Three-quarters of the survivors surveyed indicated their willingness to have an additional biopsy, regardless of whether they reported any pain or complications from their initial biopsy. Specifically, among the survivors who were willing to undergo an additional biopsy: Almost all of the survivors (82%) would do so if it would help their health care team better match treatment to their specific cancer and personalize their care, versus just being told the test was to look for mutations. In other words, understanding the end benefit of having the test is an important piece of communication. Although almost 50% reported pain or complications from their initial biopsy, this group indicated equal willingness to have another biopsy as those without any issues. If the doctor were to recommend an additional biopsy or a biopsy after the start of treatment, nearly half would definitely undergo one. About two-thirds of the survivors felt that their doctor explained the reason for getting their initial biopsy really well.

Conclusion:
The study reinforces the importance of a patient-centric model in medicine–in which meaningful and timely information is provided to patients to enable them to be partners in their own care. The study has the following implications for different stakeholders: Patients: To ask their doctor about new treatments and discuss the need for additional biopsies if necessary. Understanding the end benefit of having the test is an important piece of communication. Patient Advocacy Organizations: To educate patients and physicians about having an open dialogue to help patients become equal partners in their treatment decision-making. Physicians: To discuss the benefits and the risks of an additional biopsy with their patients and how it may help decide course of treatment.

Background:
There are limited data on factors that contribute to the development of ROS1-fusion positive cancers. A group of ROS1+ patients approached the Bonnie J. Addario Lung Cancer Foundation (ALCF) for support of ROS1 research. As a first step in this unique, patient-driven effort, we designed a survey to understand epidemiologic/clinical factors that may contribute to the development and progression of ROS1 cancers. We aim to collect data with biospecimens and make these available through an open-access data-sharing platform to accelerate ROS1 research.

Methods:
With guidance from ROS1 patients, we designed a 204-question survey, obtained Stanford University IRB approval. The survey on the ALCF website from May 18, 2016, was widely publicized through conferences, patient support networks, social media and community-based outreach. The survey questions address demographic-, clinical-, diagnostic and treatment- factors, family and reproductive history, dietary, exercise, environmental exposure and hormone and substance use. We used Z-proportions test for statistical significance defined as p<0.05.

Results:
In 53 days, 95 global patients with ROS1-fusion+ cancer responded to the survey (median age at diagnosis 56 years). Respondents were 71% female (n=52/73), 79% never smokers (49/62). 71% respondents were otherwise healthy before diagnosis (n=46/65). The majority of respondents were diagnosed with lung cancer (n=68/72); and one each with gastric, ovarian, cervical and liver cancer. 76% reported metastatic disease (n=52/68) at diagnosis with the most common site of metastases as contralateral lung (65%) and bone (46%). 52% patients reported their ROS1 cancers were not detected at diagnosis (n=35/67); 80% didnot know their specific translocation (51/64). 71% patients received molecular testing on physicians’ orders (n=45/63), with 21% self-initiating molecular testing. Despite the availability of targeted treatments and clinical trials, most patients were prescribed chemotherapy in their first (62%), second (49%), third (60%) and further lines of therapy. 76% patients reported that crizotinib was the therapy that worked best, with 96% reporting significant improvement in symptoms and QoL. We found no significant correlations between oral contraceptive/hormone/anabolic steroid use, occupational exposure, geographic area of employment/residence, family history of cancer, and incidence of ROS1+ cancer.

Conclusion:
This is a unique patient and non-profit advocacy group-driven investigation that seeks to understand factors that may influence development and treatment of ROS1 cancers. The results highlight patient-centricity, the importance of upfront molecular testing and targeted therapies. We report patient-reported experiences with ROS1 testing and durable responses to targeted treatments e.g. crizotinib. As the study is ongoing, we will update results in December 2016.

Abstract not provided

Background:
Delivering high-quality cancer care at an affordable cost is the main challenge for health care professionals and policy makers. Immunotherapy achieved encouraging results in NSCLC. PD-L1 expression is being studied as a predictive biomarker. The objective of our study is to assess the economical impact of NIVO and PEMBRO with and without the use of PD-L1 as a biomarker in the US.

Methods:
We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line treatment with NIVO or PEMBRO versus docetaxel. The model used outcomes data from RCTs and costs from the US. We included the costs of adverse events and post-progression therapies. Thereafter, we used American epidemiology data to estimate the impact of the treatment.

Results:
We included three RCTs (two with NIVO and one with PEMBRO). The estimated number of cases eligible was 37,638. Treating all patients with NIVOLUMAB would cost 1.6 billion dollars each year, increasing total oncology drug expenditure in the US by 4%. Treating only patients with PD-L1 > 1% with NIVOLUMAB would cost US$ 850 million each year and would increase total oncology drug expenditure by 2%. However, with such patient selection up to 46% of cases would not be treated and 2,509 fewer life-years would be saved. The cost of each year-of-life saved was improved by PD-L1 selection (from US$ 223,000 to US$ 186,000 thousand). Table 1 summarizes our findings. Results were similar with NIVOLUMAB and PEMBROLIZUMAB.

Scenario	QALY gain	ICER U$	Life-Years Saved	Years of life not saved	Not Treated	%	Total Cost U$	Impact on Total Cancer Drug Expenditure	Cost/LYS U$
					37,638	100
NIVO ALL COMERS	0.148	124K	7,043	0	0	0	1.6 bi	4%	223K
NIVO PD-L1 > 1%	0.201	91K	4,534	2,509	17,389	46	850 mi	2%	186K
PEMBRO PD-L1 > 1%	0.138	116K	5,302	NA	12,685	34	971 mi	2%	183K
NIVO ALL SQ/>1% NSQ	0.216	93K	5,868	1,175	13,303	35	1 bi	3%	178K
PEMBRO PD-L1 > 50%	0.164	97K	2,270	NA	26,912	72	420 mi	1%	184K

Conclusion:
The use of PD-L1 expression as a biomarker for treatment with immunotherapy decreases the overall economic impact and the cost per life-year saved. Nevertheless, the number of life-years saved with this strategy would be significantly smaller than if we choose to treat all patients. Further study and societal discussion is warranted in order to find the optimal strategy for patient selection.

Background:
Annual LDCT screening for individuals 55-74 yrs with >30 pack-year smoking history is supported by evidence from the NLST but has led to questions of implementation. Compared to organized screening (ORG), opportunistic screening (OPP) may utilize broader entry criteria and not include smoking cessation.

Methods:
Health and economic impacts of ORG using NLST entry criteria were modelled using population microsimulation (OncSim – formerly Canadian Risk Management Model v 2.3) and compared to OPP scenarios. We modeled ORG at a participation rate of 30 and 60%, with and without smoking cessation, compared to various plausible OPP scenarios: younger individuals (40-74 yrs); lesser smoking histories (10 or 20 pack-yrs). Outcomes projected to 20 years included incidence, mortality, number of scans, invasive diagnostics for false positives, and screening and treatment costs. A lifetime horizon and 3% discounting were used to estimate the incremental cost-effectiveness ratio (ICER) from a health system perspective. All costs are in 2016 CAD.

Results:
A large number of outputs can be presented. At a participation rate of 30%, average annual incremental incident cases of lung cancer with OPP for 40-74 yr-olds with 10 pack-yr histories are higher by 254 over ORG without cessation, and there would be an average 135 fewer deaths annually. However, the annual number of CT scans would increase by 433,000 on average and diagnostic tests for false positive results would increase by 1540. Average annual costs would increase by $141 M compared with ORG without cessation, resulting in an ICER of $133,000/QALY. OPP with 40-74 yr-olds having 20 and 30 pk-yr histories result in $92,147 and 74,978/QALY respectively. In all cases of OPP compared to ORG with cessation there are net losses of QALY. Notably, ORG with smoking cessation compared to ORG without yields an ICER of $2800/QALY.

Conclusion:
OPP screening results in more incident cases and fewer deaths but more cost from over-diagnosis and false positives. In Canada, an annual screening program with strict adherence to NLST entry criteria could be highly cost-effective. Jurisdictions will have to weigh the benefits and risks of LDCT scanning beyond the currently available evidence.

Background:
Effect of insurance type on lung cancer diagnosis, treatment and survival is still under debate in Asian patients living in United States.

Methods:
A total of 447,167 patients (18 to 113 years), diagnosed with lung cancer between 2004 and 2013 in the Surveillance, Epidemiology, and End Results database were analyzed. Patient demographics and clinical characteristics were compared between Asian and Non-Asian patients. In Asian patients, patient demographics and characteristics were compared among insurance types. Multivariable logistic regression analysis was performed to identify the effect of insurance types on stage at diagnosis and treatment modalities. Multivariable cox’s regression analysis was performed to identify the effect of insurance type on cancer-specific death.

Results:
Asian were significantly more frequently males (56.7% vs. 53.1%), married (62.2% vs. 50.2%), with Medicaid (17.4% vs. 8.7%), living in rural area (93.6% vs. 86.9%), in a low income county (26.3% vs. 13.4%), and stage 4 at time of diagnosis (51.1% vs. 48.0%) than non-Asian patients (all p-value < 0.001). Among 26,884 Asian lung cancer patients, uninsured were significant younger (61.1±10.8 years) than non-Medicaid (69.1±11.9 years) and Medicaid (70.7±11.7 years), p <0.001, more likely single (18.9 % vs. 8.8% vs. 13.0%); living in a high income county (41.8% vs. 30.5% vs. 38.6%); more likely to be stage IV (63.7% vs. 50.0% vs. 51.2%); and not undergo surgery (86.2% vs. 75.4% vs. 82.6%), [all p-value < 0.001). Localized disease was more frequent in non-Medicaid (21.2%) and Medicaid (17.3%) compared to uninsured (9.0), (p < 0.001).At multivariable analyses, insurance type was not associated with cancer-directed surgery and radiotherapy. Insurance was significantly associated with cancer-specific death (uninsured HR 1.37 95%CI 1.07-1.75; non-Medicaid HR 1.17 95% CI 1.07-1.28 vs Medicaid).Figure 1



Conclusion:
Insurance type affects stage at diagnosis and cancer-specific death but not surgical treatment and radiotherapy in Asian lung cancer patients.

Abstract not provided

Background:
Lung cancer has a high incidence in Brazil; approximately thirty-four thousand new cases are diagnosed each year. In Brazil, as in other countries, the majority of patients diagnosed with lung cancer are elderly. There are few studies that evaluate demographic and clinical characteristics, disease staging, treatment modalities and survival in young patients, mostly carried out in developed countries. This study aimed to describe these aspects in patients with non-small cell lung cancer (NSCLC) according to age.

Methods:
Retrospective cohort consisted of patients diagnosed with NSCLC followed in a referral hospital in São Paulo. During the monitoring the survival time was evaluated. Survival functions were calculated using the method of Kaplan-Meier. The survival stratified by age was also obtained, according to distribution of percentages (less than 55; between 55 and 72 years; older than 72 years). Differences between survival curves were determined using the log-rank test.

Results:
From January 2000 to July 2015 790 patients were followed, 165 aged less than 55 years, 423 between 55 and 72 years and 202 older than 72 years. Higher incidence of adenocarcinoma was seen at the groups up to 72 years. 575 (73%) patients with advanced disease (IIIB-IV stages) were observed. The median five-year survival was 12 months [46-4]. The survival of patients in different age groups was not different.

	<55 165	>55<72 423	>72 202	p
Male n(%)	87 (53)	279 (66)	127 (63)	0.012*
Smoke n(%)	136 (82)	363 (86)	165 (82)	0.34*
Male	78 (90)	263 (94)	121 (95)	0.21*
Female	58 (74)	100 (69)	44 (59)	0.10*
Histological type n(%)				0.13*
Adenocarcinoma	92 (56)	216 (51)	91 (45)
Squamous Cell Carcinoma	52 (32)	170 (40)	91 (45)
Staging n(%)				0.057*
IA/IIIA	34 (21)	127 (30)	52 (26)
IIIB/IV	131 (79)	294 (70)	150 (74)
Deaths n (%)	83 (50)	232 (55)	105 (52)	0.56*
Follow-up (months) Median[IIQ]	4.9 [1.3-13.2]	6.5 [2.0-16.3]	4.4 [1.4-12.9]	0.07†

*Chi-square test; † Kruskal-Wallis (Duncan test); ‡oneway ANOVA (Bonferroni test).

Conclusion:
In the age group of younger patients (<55) women predominated, histological type adenocarcinoma was more frequent, and there were more patients with advanced stage at the diagnosis and a higher percentage of smokers in both genders.

Background:
Globally, 600,000 non-smokers die due to tobacco related diseases and health care cost for tobacco related diseases are soaring especially in developing countries.Cigarette smoke contains 69 known carcinogens out of 7000 chemicals causing various health problems in children and infants including ear infections, bronchitis, pneumonia, frequent and severe asthma attacks, sudden infant death syndrome and cancer. Secondhand smoke can cause coronary heart disease, stroke and various kinds of cancer including lung cancer in adult. 2006 U.S. Surgeon General Report clearly confirmed that there is no safe level of exposure to secondhand smoke. Therefore, there is a strong need for comprehensive smoke free law in reducing the burden of tobacco use in the world.

Methods:
"Section not applicable"

Results:
Iceland is a high income country with a long history of tobacco control. The comprehensive tobacco control law was passed in 1984 which included restriction on smoking in service areas of public and private buildings, premises of health care facilities, schools, workplaces, and in public transport whereas Thailand is an upper middle income country and once had a very high smoking rate (70 percent for male and around 5 percent for female) in early 1970. Smoking ban in movie theaters and buses ordinance was issued by Bangkok Metropolitan Administration I n 1976 followed by the comprehensive interventions including smoke-free areas by the royal Thai government in 1991. As a result, the smoking prevalence went down to 32 percent in Thailand but this still demonstrated that one in three adults in 1991. It was found that the role of government and different civil society organizations in implementing smoke free policies was significant in both countries in this review paper. Although both countries issued smoke free policies, there are still challenges on implementation. Iceland try to overcome the challenges by developing comprehensive system including investigation after complaint and allocating budget for enforcement. Thailand also implemented 100% Smoke-Free Hospitals with the compliance rate of 86.4 percent according to a research in 2010. Thailand established the Thai Health Promotion Foundation (ThaiHealth) in 2001 which allowed Thailand to implement comprehensive tobacco control measures in a sustainable way. ThaiHealth used knowledge generation, social mobilization and policy advocacy called tri-power strategy in achieving the success.

Conclusion:
This paper concluded that civil society initiative and continuing efforts on tobacco control which leads to adoption of comprehensive tobacco control law is the heart of the success of tobacco control in both countries.

Background:
Despite guideline recommendations on time intervals in the care of a lung cancer patient, delays are often experienced. The goal of this study was to quantify time intervals and identify delays in the workup to treatment of non-small cell lung cancer (NSCLC) at our institution.

Methods:
A retrospective review of all NSCLC cases in the Tumor Registry at a tertiary military medical center diagnosed and treated between July 2011 and July 2014 was performed. Dates of radiographic identification of a suspicious pulmonary lesion, tissue diagnosis, evaluation by the treating specialist, and initial treatment (whether surgery, radiation, chemotherapy, or best supportive care/palliative care) were recorded. Time intervals were calculated from these dates; if any interval was more than 60 days, reasons for delays were recorded.

Results:
The median time from the identification of a suspicious pulmonary lesion to the treatment of NSCLC was 74 days (range 5-557 days) and the median time from tissue diagnosis to first treatment was 33 days (range 1-252 days) for the 148 patients included in the analysis. Even after excluding outliers, the adjusted median time from the identification of a suspicious pulmonary lesion to the treatment was 71 days. The most common reasons for treatment delay were waiting for consultant evaluations, staging procedures, repeat biopsies, or additional studies (pre-operative risk stratification, molecular testing). Only 1 patient was upstaged from time of tissue diagnosis to first treatment (from IA to IIB following resection).

Table 1: Critical time intervals

Time interval	Median	Range
Days from suspicious imaging study to first treatment	74	5-557
Days from suspicious imaging study to tissue diagnosis	34	1-556
Days from suspicious imaging study to evaluation by treating specialist	50	1-553
Days from tissue diagnosis to first treatment	33	1-252
Days from tissue diagnosis to evaluation by treating specialist Cardiothoracic surgery Radiation-oncology Medical-oncology Palliative care	20 21 21 18 15	1-157 10-56 1-157 1-64 4-48
Days from evaluation by treating specialist to first treatment Surgery Radiation Chemotherapy Best supportive care	16 23 14 16 1	1-261 6-261 1-88 1-28 1-28

Conclusion:
Several time intervals identified in the workup to initial treatment of NSCLC patients at our institution exceeded recommendations from various guidelines. These delays could be addressed with process and quality improvement projects involving a standardized NSCLC clinical care pathway.

Abstract not provided

Abstract:
Molecular alterations that are characteristic of lung tumors have been shown to be present in normal-appearing airway epithelium adjacent to lung tumors suggestive of an airway field cancerization phenomenon (1, 2). These field effects include altered gene expression, loss of heterozygosity (LOH), gene mutation and methylation and microsatellite instability (3-7). Microarray studies have pointed to expression profiles that are dissimilar between airways in smokers with and without lung cancer (8, 9). It has been recently demonstrated gene expression profiles that are shared between normal-appearing airway cells and nearby NSCLCs and that can distinguish airways of smokers with lung cancer from those without the malignancy (8). Studies from several groups suggest that the field cancerization provides biological insights into non-small cell lung carcinoma (NSCLC) ad small cell lung carcinoma (SCLC) pathogenesis and clinical opportunities for lung cancer detection (6, 8). It is important to note that smoking perpetuates inflammation throughout the exposed airway epithelium (10). This effect is pronounced in patients with Chronic Obstructive Pulmonary Disease (COPD) (10). Notably, among smokers, even after smoking cessation, airway inflammation persists while the risk of lung cancer continues to increase (10). It is not known which tumor promoting profiles in the airway field cancerization may drive lung cancer development in COPD patients. Using microarray profiling, studies have pointed to expression profiles that are dissimilar between airways in smokers with lung cancer and airways in smokers without cancer (11-13). Importantly, these gene-expression changes within the “field of injury” have been leveraged for development and validation of a clinically-relevant biomarker that can improve the diagnostic performance of bronchoscopy for detection of lung cancer (predominantly NSCLC) among smokers with suspect disease (8, 12). In addition, gene expression array analysis pointed to airway field expression profiles that are spatially and temporally modulated in early stage patients following surgery and that may be associated with disease relapse (13). Further, we have recently demonstrated that there is significant enrichment in gene expression profiles measured in both small (adjacent to tumor) and large (mainstem bronchus) airway compartments of the airway field of injury, suggesting that gene-expression changes in the large airway can serve as a surrogate for the molecular changes occurring in the airway epithelium adjacent to the tumor (9). Taken together, studies from our group and others suggest that, by sampling “normal” and relatively accessible tissue (e.g., bronchial airway), the airway field of injury provides biological insights into the earliest phases in the development of lung malignancy and potential valuable clinical opportunities such as early detection (1, 2). Identifying molecular aberrations that precede cellular morphological changes will provide biological insights into why some smokers develop lung cancer and, thus, clinical opportunities for improved lung cancer detection. References: 1. Kadara H, Wistuba, II. Field cancerization in non-small cell lung cancer: implications in disease pathogenesis. Proceedings of the American Thoracic Society. 2012;9(2):38-42. 2. Steiling K, Ryan J, Brody JS, Spira A. The field of tissue injury in the lung and airway. Cancer Prev Res. 2008;1(6):396-403. 3. Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG. Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci U S A. 1998;95(20):11891-6. 4. Mao L, Lee JS, Kurie JM, Fan YH, Lippman SM, Lee JJ, Ro JY, Broxson A, Yu R, Morice RC, Kemp BL, Khuri FR, Walsh GL, Hittelman WN, Hong WK. Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst. 1997;89(12):857-62. 5. Tang X, Shigematsu H, Bekele BN, Roth JA, Minna JD, Hong WK, Gazdar AF, Wistuba, II. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer research. 2005;65(17):7568-72. 6. Wistuba, II, Behrens C, Milchgrub S, Bryant D, Hung J, Minna JD, Gazdar AF. Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene. 1999;18(3):643-50. 7. Wistuba, II, Lam S, Behrens C, Virmani AK, Fong KM, LeRiche J, Samet JM, Srivastava S, Minna JD, Gazdar AF. Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst. 1997;89(18):1366-73. 8. Spira A, Beane JE, Shah V, Steiling K, Liu G, Schembri F, Gilman S, Dumas YM, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb C, Anderson T, Gerry N, Keane J, Lenburg ME, Brody JS. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med. 2007;13(3):361-6. 9. Kadara H, Fujimoto J, Yoo SY, Maki Y, Gower AC, Kabbout M, Garcia MM, Chow CW, Chu Z, Mendoza G, Shen L, Kalhor N, Hong WK, Moran C, Wang J, Spira A, Coombes KR, Wistuba, II. Transcriptomic architecture of the adjacent airway field cancerization in non-small cell lung cancer. J Natl Cancer Inst. 2014;106(3):dju004. 10. Punturieri A, Szabo E, Croxton TL, Shapiro SD, Dubinett SM. Lung cancer and chronic obstructive pulmonary disease: needs and opportunities for integrated research. J Natl Cancer Inst. 2009;101(8):554-9. 11. Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams A, Liu G, Szabo E, Brody J, Massion PP, Lenburg ME, Lam S, Bild AH, Spira A. Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med.2(26):26ra5. 12. Silvestri GA, Vachani A, Whitney D, Elashoff M, Porta Smith K, Ferguson JS, Parsons E, Mitra N, Brody J, Lenburg ME, Spira A, Team AS. A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer. N Engl J Med. 2015;373(3):243-51. 13. Kadara H, Shen L, Fujimoto J, Saintigny P, Chow CW, Lang W, Chu Z, Garcia M, Kabbout M, Fan YH, Behrens C, Liu DA, Mao L, Lee JJ, Gold KA, Wang J, Coombes KR, Kim ES, Hong WK, Wistuba, II. Characterizing the molecular spatial and temporal field of injury in early-stage smoker non-small cell lung cancer patients after definitive surgery by expression profiling. Cancer prevention research. 2013;6(1):8-17.

Abstract:
Low-dose computed tomography for high-risk individuals has for the first time demonstrated unequivocally that early detection save lives. The currently accepted screening strategy comes at the cost of a high rate of false positive findings while still missing a large percentage of the cases. Therefore, there is increasing interest in developing strategies to better estimate the risk of an individual to develop lung cancer, to increase the sensitivity of the screening process, to reduce screening costs and to reduce the numbers of individuals harmed by screening and follow-up interventions. New molecular biomarkers candidates show promise to improve lung cancer outcomes. This review discusses the current state of biomarker research in lung cancer screening with the primary focus on risk assessment. The rationale for developing biomarkers for the early detection of lung cancer is very strong and well established. It stems from the fact that, at the population level, the earlier we detect the disease, the better the outcome and the lower the health care cost. The impetus for biomarker development has grown stronger since the NLST trial demonstrated that early detection via chest CT screening reduced the relative risk for lung cancer death in the high risk individuals. Low dose chest CT in this group alone may save up to 12,000 lives a year, but it represents only about 8 % of individuals dying of this disease every year. Thus, much is to be done to capture these lung cancers that escape chest CT screening as currently recommended despite its high sensitivity and specificity. The reason for limited detection relates to how many at-risk individuals are studied with CT and to how we best define this risk. Detection and careful management of indeterminate pulmonary nodules are integral parts of this effort. Lung cancer screening using chest CT also raises many questions, some of which could be addressed with well poised biomarkers. For example, who is at utmost risk for lung cancer? How do we expand the screening criteria from the NLST without causing more harm than good? Once the CT screening studies are done, how do we approach a non-invasive diagnosis of lung cancer? How do we prevent the overdiagnosis bias? Here we focus on biomarkers that could be used in a risk assessment evaluation for screening programs. We will discuss current molecular biomarkers of risk assessment in those without measurable disease and before a chest CT has been done. Consideration of the use of such biomarkers should trigger a discussion with the patient before ordering it to address the intent of the test and the implications of the possible results. Many biomarkers have been developed over the years to predict tumor development. Let us consider the characteristics of such a biomarker to assess the risk of lung cancer. For screening purposes, given the low prevalence of disease, a strong negative predictive value (NPV) of a test is a very attractive feature. High specificity on the other hand is always desirable so we do not overcall cancers (false positive). Should such a test be positive, it would push individuals into a higher risk group to consider appropriate surveillance. The biomarker could measure a genetic risk (e.g. altered metabolism of carcinogens, DNA repair machinery abnormalities, predisposition to inflammation, or germline mutations) or the influence of the environment on tumor development (exposure to carcinogens or surrogates of risk such as epigenetic changes in the airway epithelium or the prevalence of preinvasive lesions). There has been recent interest in the potential for genetic variants to give insight into the pathogenesis of lung cancer. These variants indicate that there is great heterogeneity in mechanisms of disease development that is modulated by inherited genetic variation. With these come the opportunity to improve models predicting lung cancer risk. A larger question of timeliness of biomarker use in clinical practice will be discussed during the presentation. What are the risk and benefits of precision screening? Are current risk prediction models safe to use or robust to guarantee an advantage over current standard of care? There is a clear need to evaluate the benefit of risk assessment biomarkers with repeated measures over time. The assumption is that as risk increases, molecular moieties should be more readily available (e.g. in the circulation) over time. This may be true for tumor specific antigens and ctDNA, but would not apply to genetic risk. Statistical models could test the ability of different biomarkers to complement each other in a single population, in order to eventually determine those that could be tested prospectively. Given biomarkers' non-specificity and commonality in predicting diseases, modeling multiple markers of the same clinical diagnostic criteria can be used to develop more accurate individual and cumulative risk estimates for specific diseases. We should therefore consider a joint effects approach to determine individual biomarker associations as well as to ascertain the impact of simultaneous increases in multiple biomarker concentrations on the diagnosis of lung cancer. Biomarkers of risk would ideally be tested prospectively in a randomized clinical trial. However, given the relatively low prevalence of this disease, the number needed to screen may be prohibitive; therefore the development of registries is most appropriate. Registries are longitudinal cohort prospective studies where a biomarker is introduced but does not force providers to change their management. The lead time to diagnosis may be sufficient to cause a stage shift and therefore improve outcome. Finally, it is through better understanding of the biology of cancer development and of preinvasive lesions that we will shed further light into the field of biomarker research.

Abstract not provided

Abstract not provided

Abstract:
The UKLS Trial and cost effectiveness The pilot UKLS lung cancer RCT screening trial recruited 4,000 individuals [1], using the LLP~v2~ risk model (5% risk over 5 years) [2]. The lessons learnt from the UKLS CT pilot screening trial are: UKLS – A Population based trial – all IMD’s (socioeconomic groups) included [1]. Risk Stratification (LLP~v2~ 5 % risk over 5 years) [2] Volumetric assessment of CT detected nodules [3]. Care Pathway – Management pathway implemented [3]. Early Stage Disease (Stage 1 68%: Stage I&II 86%) [4] High Proportion suitable for Surgery (83%) [4] 1.7% lung cancers identified at baseline scan [1] Benign Resection rate – 10.3% (NLST 27%)[1] Psychological impact – transient not significant [5, 6] Cost effectiveness modelling within NICE parameters [1] The cost effectiveness of the UKLS trial has been modelled and compared with that of the US National Lung Screening Trial (NLST), which has published an estimate of $81,000 per quality-adjusted life-year (QALY) as its mean incremental cost-effectiveness ratio (ICER) [7]. All UKLS cost estimates were based on 2011-12 NHS tariffs (Costs provided in $: £1=$1.5 on 30-11-15). Owing to the brief duration of the trial, observations relevant to economic evaluation were limited to cost-incurring events associated with screening and the initial management of screen-detected cancers. Expected outcomes of the cancers detected were simulated on the basis of both life tables and published survival data from other studies. The costs incurred from UKLS are those of baseline and repeat screens ($424,072), diagnostic workup ($113,478), and treatment ($449,243), which totaled $1,036794 (95% CI, $719,332 to $1,350,766). Recruitment costs ($15) per person for invitation and selection) were modelled from the UK colorectal screening programme and we assumed a participation rate of 30% of those invited. The gross current costs of the programme amounted to $1,133,217 (CI $817,887 to $1,450,610). Summary of findings: The ICER of screen-detection compared with symptomatic detection was estimated at $9495 per life-year gained. Using data from previous studies, we associated quality of life weights with the estimated survival gains, enabling us to report outcomes as QALYs. On this basis, the ICER equaled $12,709 per QALY gained (CI $ 8280 to $18966). The difference in cost effectiveness between NLST and UKLS as suggested by the estimated ICERs is more apparent than real. Most of the discrepancy can be explained by differences between settings in (i) local unit costs, (ii) intensity of resource use, (iii) number of screening rounds and (iv) disease prevalence in the target population. Thus, UKLS selected high-risk subjects only whereas NLST screened a general population, yet the latter reported an ICER as low as $32,000 for its highest-risk quintile. Expected QALY gains from screen-detection were similar in both trials. Figure 1

Abstract:
When bronchoscopy is performed for peripheral pulmonary lesions (PPLs), a radial ultrasonic probe can be inserted from the working channel of the bronchoscope to reach the PPL[1]. We began using this technique of endobronchial ultrasonography (EBUS) in 1994. EBUS using a guide sheath (GS) also began in 1996[2]. We would like to explain the technique and advantages of diagnosing PPLs using EBUS, GS, Navigation, and etc. 1) Radial ultrasonic miniature-probe A radial probe emits US while being rotated 360°; the reflected US waveform is rendered as an image. The radial probe scans from the bronchial lumen to provide a short-axis image of the bronchial and para-bronchial tissue. 2) Analyzing the internal structure of peripheral pulmonary lesions with a radial mini-probe EBUS imaging before surgery has been compared with histopathologic findings of surgically resected tissue to determine the internal structures of PPLs that can be depicted by EBUS[3]. PPLs can be classified as heterogeneous or homogeneous based on irregularities in brightness within lesions seen on EBUS. Internal structures within peripheral lesions that can be identified by EBUS include patent blood vessels, patent bronchi, hemorrhage, calcification, dilated bronchi, necrosis, and small amounts of air in alveoli. 3) EBUS using a guide sheath (EBUS-GS)[ 1, 2] The GS-covered probe is advanced to the PPL, then after confirmation by EBUS that the lesion has been reached, the probe is removed before inserting the brush and biopsy forceps through the GS that is held in place in the lesion. This technique enables cytology and biopsy to be performed several times with minimal risk of bleeding. 4) Insertion of the bronchoscope (saline immersion technique) After observing the bronchial lumen, the bronchoscope should be advanced while visualizing the branches to the bronchus near the peripheral lesion. Upon reaching a position where further advancement is not possible, flushing of 1-ml saline (total 5-10 ml) several times is performed through the working channel of the bronchoscope; this is done to fill the bronchus, remove any sputum, and visualize the lumen. The GS-covered probe is then inserted from the working channel into the bronchus. In cases of ground glass nodule (GGN), we do not perform the saline immersion technique. Because the saline immersion technique will occur EBUS images of hyperechoic points which resemble EBUS image of GGN. 5) EBUS visualization The operator advances the US probe from the working channel of the 4-mm bronchoscope towards the periphery and stops when some resistance is felt. The duration of X-ray fluoroscopy should be limited as much as possible; also, an iris of the fluoroscopy machine should be used for fluoroscopy. Scanning while pulling back the probe from the distal site to the proximal site reduces strain on the probe and provides clear EBUS images. We have reported that EBUS imaging of PPLs can be used to diagnose and assess the degree of differentiation between benign and malignant lesions[3]. PPLs are classified as type I if the internal echoes are homogeneous, type III if the internal echoes are heterogeneous, and type II if there are mainly hyperechoic lines and dots near the probe. About 92% of type I lesions were benign, whereas 99% of type II and type III lesions were malignant. The positional relationship between the probe and a PPL is classified as "within" (probe placement within a lesion), when the 360° area around the probe is entirely surrounded by the lesion; and "adjacent to" (probe is in contact with a lesion) when a lesion is depicted, but the 360° area around the probe is not entirely surrounded by the lesion. Higher diagnostic yields have also been reported for lesions with a positive bronchus sign on computed tomography. Minezawa et al.[4] reported that the CT bronchus sign was a significant predictive factor for successful bronchoscopic diagnosis in the multivariate analysis. We believe that bronchoscopists should trace the accurate bronchus leading to the PPL on CT axial images. When the lesion located in the middle lobe, the lingular segment, or bilateral lower lobes, we inverse CT axial images right to left, or left to right for watching the bronchus from the cranial site. When the lesion located in the right upper lobe, we rotate CT axial images counterclockwise 90 degrees. When the lesion located in the left superior segment, we rotate CT axial images clockwise 90 degrees. While tracing the bronchus on CT images, we could draw the illustration of the bronchus leading to PPLs. We usually use virtual bronchoscopic navigation (VBN) and compare the hand-written illustration of the bronchus leading to PPLs. Asano et al.[5 ]reported that the diagnostic yield by EBUS-GS and VBN was between 63.3 and 84.4% in reports on VBN for PPLs searched in PubMed as of November 2013. When the ultrasonic probe advanced to the different bronchus a little far from the target lesion, EBUS image is invisible. In this case, we should change the direction of the tip of the bronchoscope using the up and down lever of the bronchoscope under fluoroscopy. We select the direction of the tip of the bronchoscope for facing the target lesion, and pull back and push the probe/GS for trying to insert the target lesion. When the ultrasonic probe advanced to the bronchus adjacent to the target lesion, EBUS image is called as “adjacent to”. In this case, we could change the direction of the tip of the bronchoscope using the up and down lever of the bronchoscope under the EBUS image. We use the up or down lever of the bronchoscope for changing the position of the probe and GS (probe/GS) to be close to the target lesion on EBUS image. Then we keep the same angle of the tip of the bronchoscope, and pull back and push the probe/GS for trying to insert the target lesion. 6) Cytology and tissue biopsy from the guide sheath The GS tip is placed within or adjacent to the PPL before passing the brush and biopsy forceps through the GS. References Kurimoto N, Fielding D, Musani A. Endobronchial Ultrasonography. 2011, Willy Blackwell Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Miyazu Y, Murayama M. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. CHEST 2004; 126: 959-65. Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography. CHEST 2002; 122: 1887-94 Minezawa T, Okamura T, Yatsuya H, et al. Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study. BMC Med Imaging. 2015 21; 15:21 Asano F, Eberhardt R, Herth F. Virtual Bronchoscopic Navigation for Peripheral Pulmonary Lesions. Respiration 2014; 88: 430-440

Abstract:
Despite the advances in surgical treatment and multimodality treatment, lung cancer is still the leading cause of death from malignant disease worldwide. Accurate staging is important not only to determine the prognosis but also to decide the most suitable treatment plan. During the staging process of non-small cell lung cancer (NSCLC), mediastinal lymph node staging is one of the most important factors that affect the patient outcome. Non-invasive staging such as computed tomography (CT) and positron emission tomography (PET) indicate size and metabolic activity, respectively. However imaging alone is inaccurate and therefore tissue sampling is the preferred and most reliable. Surgical staging by mediastinoscopy has been the gold standard for mediastinal lymph node staging but requires general anesthesia and complications cannot be ignored. Endoscopic ultrasound techniques provide a minimally invasive alternative for surgical staging. The current available endoscopic ultrasound techniques for mediastinal staging include transesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). Both procedures can be performed in an outpatient setting under local anesthesia. EUS-FNA is a sensitive and safe method of evaluating the inferior mediastinal nodes (stations 7, 8, and 9) and some parts of the anterior mediastinal nodes if the lymph nodes are accessible from the esophagus. However, in spite of the strength of EUS-FNA for evaluating the inferior mediastinal nodes, its ability to evaluate lesions anterior to the trachea is limited. On the other hand, EBUS-TBNA has reach to the paratracheal and subcarinal (stations 2R, 2L, 4R, 4L, 7), as well as the N1 lymph nodes (stations 10, 11, 12). In experienced hands, EBUS can be used through the esophagus for a EUS-like approach to the inferior mediastinal lymph nodes. Thus, EUS-FNA and EBUS-TBNA are complementary methods for lymph node staging in lung cancer and most of the mediastinum and the hilum can be evaluated with these endoscopic procedures. Aortic nodes (stations 5 and 6) are exceptions and must be evaluated by surgical methods (anterior mediastinotomy, VATS, thoracotomy). Based on the current evidence, EBUS-TBNA and EUS-FNA presents a minimally invasive endoscopic procedure as an alternative to mediastinoscopy for mediastinal staging of NSCLC with discrete N2 or N3 lymph node enlargement, provided negative results are confirmed by surgical staging. EBUS-TBNA can access all lymph nodes accessible by mediastinoscopy as well as hilar (N1) lymph nodes. EUS-FNA has access to the inferior mediastinal lymph nodes not accessible by mediastinoscopy. EBUS-TBNA and/or EUS-FNA have in fact replaced mediastinoscopy in many patients with diffuse mediastinal adenopathy, where a simple tissue diagnosis is required to determine treatment. When combined the techniques offer safe and accurate assessment of mediastinum, with accuracy surpassing that of the pervious gold standard – cervical mediastinoscopy. EBUS-TBNA and/or EUS-FNA can also be repeated with ease and have been used for mediastinal restaging in patients who underwent neoadjuvant therapy in preparation for definitive surgical intervention. Ultrasound image analysis of lymph nodes may assist bronchoscopists during EBUS-TBNA or EUS-FNA. Standard sonographic classification of lymph nodes can help characterize mediastinal and hilar lymph nodes as benign or malignant, which may guide the decision on which lymph nodes to sample. Newer imaging technology such as elastography can potentially enhance US guided image analysis of the lymph nodes.

Abstract not provided

Abstract:
Lung cancer is the second most common cancer in both men and women In men prostate cancer, while in women breast cancer is more common. About 14% of all new cancers are lung cancers. The American Cancer Society’s estimates for lung cancer in the United States for 2016 are: About 224,390 new cases of lung cancer (117,920 in men and 106,470 in women) About 158,080 deaths from lung cancer (85,920 in men and 72,160 in women) Lung cancer is by far the leading cause of cancer death among both men and women; about 1 out of 4 cancer deaths are from lung cancer. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. One third of the new lung cancer cases are candidates for surgery, and about half of the rest develops some kind of major airways involvement. This can be endobronchial tumor, extrinsic compression or combined. Besides lung cancer, metastases from other types of tumors are also candidates for intrabronchial treatments. There are different methods available for treating endobronchial malignancies, in most of the cases the combination of two or more procedure needed to reach optimal result. To reestablish the airway patency improves quality of life, and provides sufficient time to apply different lung cancer treatment, chemo, radio and immunotherapy Methods available include mechanical debulking, use of different types of laser, electrocautery, cryotherapy, intraluminal brachytherapy, argon-plasma coagulation, and microvawe instruments. Different types of silicon and self expandable metallic stents are useful for keeping the airways open after successful reopening. Balloon dilatation may help to insert stent to the compressed airways. The use of locally installed substances like chemo, different angiogenesis inhibitors are in the focus again. With the use of endobronchial ultrasound the needle can easily be inserted into the peripheral or central tumor, and lymphnodes. Most of the procedures are done under general anesthesia, with the use of rigid bronchoscope. Ideally the bronchoscopist can choose from the different methods available, using the best appropriate one in the given situation. Sufficient training is necessary before starting each new method. Simulation, low fidelity models are available to learn without having the unnecessary risk in a real case. One has to be prepared for treating different complications, such as heavy bleeding from the tumor, or bleeding caused by the procedure itself. Well trained personnel is a must to start with these kind of procedures. Anesthesiologist, assistants trained in endoscopic procedures are essential before starting the procedure.

Abstract:
Muscle sparing thoracotomy has been a standard approach in thoracic surgery for a long time. Minimal invasive approaches have gained a widespread acceptance recently and were included in the treatment guidelines for early stage NSCLC by several societies. Prospective randomized trials comparing minimal invasive approaches versus muscle sparing thoracotomy in stage I NSCLC have already been performed more than twenty years ago and demonstrated equal morbidity and mortality. Nevertheless it took until 2013 that the American College of Chest Physician guidelines recommended a VATS approach for clinical stage I NSCLC over a thoracotomy in experienced centers (1). No recommendation is made for more advanced stages. When analyzing national registry data still a high percentage of procedures in performed in an open way. This means that in current practice thoracotomy is still used as a standard approach by many surgeons. Minimal invasive approaches – both videothoracoscopic and robotic – are not different operations but different approaches towards performing an operation. It has been proven in several studies that in early stage lung cancer minimal invasive approaches in its various form lead at least to equivalent or even better oncologic outcome compared to an open approach. Nevertheless in more advanced stages this proof is lacking. Experienced centers reported individual series of minimal invasive approaches towards advanced procedures such as sleeve resection, pneumonectomy, chest wall resection and Pancoast tumor resection. While this is technically feasible no data on long-term outcome of larger patient cohorts are available and an open approach is considered standard in these cases. Thus for tumors with invasion of hilar structures or sleeve resection a muscle sparing thoracotomy currently remains a standard approach. Perceived advantages of minimal invasive approaches – VATS as well as RATS – include less pain, fewer complications, shorter length of stay, faster return to normal activity and higher rate of adjuvant chemotherapy compliance. There are a few single center studies challenging these assumptions (2,3) as well as a recent analysis of Danish national data (4), however the majority of studies are in favor of minimal invasive approaches. In summary muscle sparing thoracotomy remains a standard approach for advanced stage tumors, whereas early stage lung cancer should be treated minimally invasive in experienced centers. References 1) Detterbeck FC1, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):7S-37S. 2) Rizk NP, Ghanie A, Hsu M, Bains MS, Downey RJ, Sarkaria IS, Finley DJ, Adusumilli PS, Huang J, Sima CS, Burkhalter JE, Park BJ, Rusch VW. A prospective trial comparing pain and quality of life measures after anatomic lung resection using thoracoscopy or thoracotomy. Ann Thorac Surg. 2014 Oct;98(4):1160-6. 3) Kuritzky AM, Aswad BI, Jones RN, Ng T. Lobectomy by Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy for Stage I Lung Cancer: A Critical Evaluation of Short- and Long-Term Outcomes. J Am Coll Surg. 2015 Jun;220(6):1044-53 4) Licht PB, Schytte T, Jakobsen E. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy. Ann Thorac Surg. 2014 Aug;98(2):411-5

Abstract:
Since the introduction of the videothoracoscopic anatomical lung resections in the early 90-ties both indications and contraidications for this type of approach have changed dramatically (1,2). There is common agreement that the oncological principles during surgery for lung cancer have to be the same regardless the type of approach: standard, minimally invasive (MIS – VATS multiportal or uniportal, intubated or non-intubated) or robotic. It regards predominantly requirements such like careful and atraumatic dissection, sufficient free-of-neoplasm margins and proper lymphadenectomy (standard or extended). Keeping it in mind we have to admit that stage I NSCLC seems „ideal” indication for MIS, particularly for less experienced surgeons. This type of surgery (MIS for stage I) is widely accepted and performed worldwide in thousands of cases. However, many experienced centers and surgeons have moved the borders forward treating more advanced cases by MIS with acceptable results regarding complications, mortlity, conversion rate or quality of lymphadenectomy. Gonzalez-Rivas presented the series of 43 advanced patients (tumors bigger > 5cm, T3 or T4, treated by neoadjuvant chemo- or radiotherapy) who were treated by uniportal VATS with good results comparable with earlier stages (3). Authors stated that „Skilled VATS surgeons can perform 90% or more of their lobctomies thoracoscopically, reserving thoracotomy only for huge tumors or complex bronchovascular reconstructions”. Large multicenter series of more than 400 advanced cases treated by VATS approach compared with propensity score matched open thoracotomy group with no differences in overall survival was published by Cao et al. (4). According to the VATS Consensus Statement (among 50 international experts to establish a standardized practice of VATS lobectomy after 20 years of clinical experience) eligibility for VATS lobectomy should include tumors <7cm and N0 or N1 status. Chest wall involvement was considered contraindication while centrality of tumour was considered a relative contraindication when invading hilar structures (5). This important statement is widely accepted however some surgeons consider it too restrictive regarding chest wall invasion. Currently there is a relatively small (but growing) group of thoracic surgeons who are performing double-sleeve (pulmonary vessels and bronchi) and carinal resections by MIS – extremely complex procedures even in open surgery (6). It requires modern instruments, sutures and definitely is not a procedure for beginners. Published series are small and overall experience is limited but this initial efforts are good example of the continuos drive of thoracic surgeons community to move indications for MIS further and further. Advanced NSCLC cases started to be treated by MIS just few years ago and there are no prospective randomised studies available in medical literature therefore we cannot definitively compare and assess the long term results but keeping in mind that the main oncological principles should be preserved and remain the same in every type of surgical approach we can expect comparable and similar results as it was reported in currently published papers. We all know that generally speaking the future is unpredictable but inevitable from the other side. Considering MIS in advanced NSCLC cases we can state with just minimal exagerration that the future is now. Selected references: 1. Roviaro G, Varoli F, Vergani C et al.: Long term survival after videothoracoscopic lobectomy for stage I lung cancer. Chest 2004;126:725-732 2. Hanna JM, Berry MF, D`Amico TA: Contraindications of videoassisted thracoscopic surgical lobectomy and determinants of conversion to open. J Thorac Dis 2013;5:182-189 3. Gonzalez-Rivas D, Fieira E, Delgado M et al.: Is uniportal thoracoscopic surgery a feasible approach for advanced stages of NSCLC? J Thorac Dis 2014;6:641-648 4. Cao C, Zhu ZH, Yan TD et al.: Videoassisted thoracic surgery versus open thoracotomy for NSCLC: a propensity score analysis based on a multi-institutional registry. Eur J Cardiothorac Surg 2013;44:849-54 5. Yan TD, Cao C, D`Amico TA et al.: Videoassisted thoracoscopic surgery lobectomy at 20 years: a consensus statement. Eur J Cardiothorac Surg 2014;45:633-639 6. Lyscov A, Obukhova T, Ryabova V et al.: Double-sleeve and carinal resections using the uniportal VATS technique: a single centre experience. J Thorac Dis 2016;8 (suppl 3):235-241

Abstract not provided

Abstract:
Introduction Uniportal video-assisted thoracic surgery (VATS) has been established as an alternative surgical approach for the treatment of most intrathoracic conditions. The potential benefits of a better view, anatomic instrumentation, better cosmesis and potential less postoperative pain and paraesthesia have led this approach to become of increasing interest worldwide. Performing surgery through a single incision approach represents an evolution of VATS to a less invasive approach. The early period of uniportal VATS development was focused on minor procedures until the second phase uniportal VATS started in 2010 with the development of the technique for major pulmonary resections. The creation of specific uniportal VATS programs in high volume centers like the Shanghai pulmonary hospital (the biggest thoracic program in the world with more than 8000 major resections per year) has contributed to spread out the technique to a large number of surgeons from all over the world in a short period of time. Surgical technique Uniportal VATS represents a radical change in the approach to lung resection compared to the conventional three-port VATS. Since the placement of all the surgical instruments and the camera is done through the same incision, Uniportal VATS can pose a challenge for both the surgeon and the assistant. The surgeon and the assistant should be positioned in front of the patient in order to have the same thoracoscopic vision during all steps of the procedure and experience more coordinated movements. Even though the field of vision is only obtained through the anterior access site, the combined movements of the thoracoscope along the incision will create different angles of vision (in this context, a 30 degree thoracoscope is recommended to achieve a panoramic view). The advantage of using the thoracoscope in coordination with the instruments is that the vision is directed to the target tissue, bringing the instruments to address the target lesion from a direct, sagittal perspective. Instruments must preferably be long and curved to allow the insertion of 3 or 4 instruments simultaneously.Optimal exposure of the lung is vital in order to facilitate the dissection of the structures and to avoid instrument interference. The rule of thumb is that for any lobectomy, the Uniport is best sited between the mid- and anterior axillary lines in the 5[th] intercostal space. This slightly anterior position takes advantage of the naturally wider intercostal spaces at the front of the human body. If the wound is sited too high – in the 4[th] space for an upper lobectomy – the dissection of the hilar vessels may be easier, but the instruments enter directly towards the hilum so that there is a smaller angle for the stapler to pass without impinging on the structures behind. If the wound is too low, there may be a good angle for the stapler to pass, but the distance to the hilum becomes too great and the arc in which instruments can be placed towards the hilum becomes too narrow – leading to more chance of ‘fencing’ between the instruments and camera. The incision itself is typically 3-4cm long, although longer incisions can be used (e.g. for an inexperienced surgeon, large tumor, thicker chest wall, etc) without any obvious disadvantage to the patient. It is helpful to rotate the surgical table away from surgeons during the hilar dissection and division of structures, and towards the surgeons for the lymph node dissection. For most of the surgical steps the thoracoscope is usually placed at the posterior part of the utility incision working with the instruments in the anterior part. For lower lobectomies the normal sequence of dissection is as follows: inferior pulmonary ligament, inferior pulmonary vein, pulmonary artery, bronchus and finally completion of the fissure. In case of upper lobectomies, the pulmonary artery is normally divided first, followed by vein, bronchus and fissure. When the lobectomy is completed, the lobe is removed in a protective bag and a systematic lymph node dissection is accomplished. The intercostal spaces are infiltrated with bupivacaine at the end of the surgery under thoracoscopic view. A single-chest tube is placed in the posterior part of the incision. We do not routinely employ epidural or paravertebral catheters. Future Recent industry improvements such as the specifically designed surgical instrumentation with double articulation, improvements in high definition video-camera systems, new energy devices and more narrower and angulated curved tip staplers have made single-port VATS, for major lung resections, easier to adopt and learn than conventional VATS. The demonstrated benefits of geometrical characteristics of the technique enables expert surgeons to perform complex cases and reconstructive techniques, such as broncho-vascular procedures or even carinal resections. The future of the thoracic surgery is based on the evolution of minimally invasive procedures and innovations directed towards reducing even more the surgical and anaesthetic trauma. We can expect more developments of subcostal or embryonic natural orifice translumenal endoscopic surgery access, evolution in anaesthesia strategies, and cross-discipline imaging-assisted lesion localization for single-port VATS procedures. Improvements in anaesthetic techniques such as non-intubated or awake uniportal VATS,may further quicken postoperative recovery allowing the tumor resection to be performed in an ambulatory setting. Furthermore, the need to reduce the risk of intercostal nerve damage associated with the transthoracic incision has led to the recent development of uniportal subxiphoid VATS technique for major pulmomary resections. We truly believe in the use of the uniportal approach, combined with yet-to-come 3D image systems (adapted on the screen, no glasses) and single port robotic technology and wireless cameras in awake patients. We understand that the future goes in the direction of digital technology which will facilitate the adoption of single-port technique worldwide in the next coming years.

Abstract not provided

Abstract not provided

Abstract not provided

Abstract:
Preclinical drug screening and biomarker discovery in the NCI-60 cancer cell line panel as well as the xenograft developed by growing these cell lines subcutaneously in immunodeficient mice have repeatedly failed to predict clinical responses. In an attempt to circumvent the limited predictive values of conventional preclinical models, there has been increasing attention in the development and characterization of Patient-derived tumor xenograft (PDX) models. The PDX models, which were created by direct implantation of patient’s tumor in immunodeficient mice, have shown to reflect principal histologic and genetic characteristics of original patient tumors and retain tumor heterogeneity better than any other preclinical model. These models have been shown to be predictive of clinical outcomes and are being used for translational research, preclinical drug screening and biomarker identification and validation. The PDX model may also be used in the application of ‘co-clinical trial’ approach, in which it is developed from a patient enrolled in a clinical trial and treated with the same experimental agents to emulate clinical response. This strategy permits the assessment of drug response simultaneously in the patient and mouse model, providing an interesting platform to investigate resistance mechanism, predictive biomarkers and novel combination strategies in a real-time manner. I will present the utility of PDX models, which faithfully replicated the histologic, genomic and pharmacologic features observed in the original patients, and ‘co-clinical trial’ that mirror a phase II trial of agents targeting fibroblast growth factor receptor (FGFR) in non-small cell lung cancer.

Abstract not provided