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Introduction The impact of clinical trial participation on overall survival is unclear. We hypothesized that enrollment in a therapeutic drug clinical trial is associated with longer overall survival in patients with metastatic non-small cell lung cancer (NSCLC). Patients and Methods We linked electronic medical record and Washington State cancer registry data to identify patients with metastatic NSCLC diagnosed between January 1, 2007, and December 31, 2015 who received treatment at a National Cancer Institute–designated cancer center. The exposure was trial enrollment. The primary outcome was overall survival, defined as the date of second-line treatment initiation to date of death or last follow-up. We used a conditional landmark analysis starting at the date of second-line treatment initiation and propensity scores with inverse probability of treatment weighting to estimate the association between trial enrollment and survival. Results Of 215 patients, 40 (19%) participated in a second-line trial. Trial participants were more likely to be never smokers (45% vs 27%), have a good performance status (88% vs 77%) and have EGFR (48% vs 14%) and ALK mutations (8% vs 5%) than nonparticipants. Trial participants had similar overall survival to nonparticipants (HR 1.05; 95% CI, 0.72, 1.53; p = 0.81) after adjusting for sociodemographic and disease characteristics. Conclusion Accounting for the immortal time bias and selection bias, trial participation does not appear detrimental to survival. This finding may be reassuring to patients and supports programs and policies to improve clinical trial access.

Introduction We assessed the proportion of patients with advanced epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive non–small-cell lung cancer (NSCLC) who receive tyrosine kinase inhibitors (TKIs) in the real-world, predictors of TKI use, and impact of TKI therapy on overall survival (OS). Materials and Methods We identified patients diagnosed with stage IV EGFR+ and ALK+ positive NSCLC from January 1, 2010 to December 31, 2018, in the Cancer Surveillance System registry and linked their records to Medicare and commercial insurance claims. We reported the proportions of patients with 1 or more TKI claims versus no TKI claims and used logistic regression to identify predictors of TKI use. We evaluated the effect of TKI use on OS by applying extended Cox proportional hazard models with TKI use as a time-dependent exposure and landmark analysis in a subcohort (N = 105). We adjusted Cox models for confounding patient characteristics. Results Of 117 eligible patients (median age = 69; 62% women; 88% EGFR+), 21 (17.9%) had no TKI claims. Diagnosis in 2015 to 2018 was independently associated with lower likelihood of TKI therapy compared with 2010 to 2014 (adjusted odds ratio, 0.29; P = .020). TKI use was associated with longer OS in a multivariate extended Cox model and in the landmark analysis (adjusted hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.33; 0.99; P = .048; adjusted HR, 0.55; 95% CI, 0.30; 1.00; P = .050). Conclusion Approximately 18% of patients with advanced EGFR+ and ALK+ positive NSCLC do not receive TKIs and have inferior survival. Further studies need to investigate barriers of access to TKIs in biomarker-selected patients.

PURPOSE: The costs associated with clinical trial enrollment remain uncertain. We hypothesized that trial participation is associated with decreased total direct medical costs to health care payers in metastatic non–small-cell lung cancer. METHODS: In this retrospective cohort study, we linked clinical data from electronic medical records to sociodemographic data from a cancer registry and claims data from Medicare and two private insurance plans. We used a difference-in-difference analysis to estimate mean per patient per month total direct medical costs for patients enrolled on a second-line (2L) trial versus patients receiving standard-of-care 2L systemic therapy. RESULTS: Among 70 eligible patients, the difference-in-difference of mean per patient per month total direct medical costs between 2L trial participants and nonparticipants was –$6,663 ( P = .01), for a mean savings of $45,308 per patient for the duration of 2L trial therapy. In a secondary analysis by primary insurance payer, this difference-in-difference was –$5,526 ( P = .26) for patients with commercial insurance and –$7,432 ( P = .01) for patients with Medicare. CONCLUSION: Participation in a 2L trial was associated with a $6,663 per month cost savings to health care payers for the duration of trial participation. Further studies are necessary to elucidate differences in cost savings from trial participation for Medicare and commercial payers. If confirmed, these results support health care payer investment in programs to improve clinical trial access and enrollment.

PURPOSE: We investigated the association of out-of-pocket (OOP) costs for tyrosine kinase inhibitors (TKIs) with overall survival (OS) in epidermal growth factor receptor ( EGFR)- and anaplastic lymphoma kinase ( ALK)-positive advanced non–small-cell lung cancer (NSCLC). We secondarily investigated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), and TKI discontinuation. METHODS: We used the Hutchinson Institute for Cancer Outcomes Research registry-claims database to identify patients with stage IV EGFR- or ALK-positive NSCLC; ≥ 1 claims for EGFR or ALK TKIs; and ≥ 3-month survival from TKI initiation. We estimated the average monthly TKI OOP costs per patient up to 3 months from TKI initiation, categorizing patients into quartiles of TKI OOP costs (Q1 < Q2 < Q3 < Q4). We conducted landmark analysis at 3 months from TKI initiation to compare Q1-3 v Q4 TKI OOP costs with respect to OS, TKI DOT, TKI adherence, and TKI discontinuation. RESULTS: Seventy-eight and twenty-seven patients comprised the Q1-3 and Q4 groups, respectively. Median monthly TKI OOP costs were $1,431 (Q1-3) v $2,888 (Q4). Compared with Q1-3, Q4 patients had inferior OS (adjusted hazard ratio [HR], 1.85; [95% CI, 1.11 to 3.10], similar TKI DOT (adjusted HR, 1.06; 95% CI, 0.53 to 2.15), decreased TKI adherence (adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76), and higher TKI discontinuation rate (adjusted OR, 8.75; 95% CI, 2.59 to 29.52). CONCLUSION: Among patients with advanced EGFR- and ALK-positive NSCLC, higher TKI OOP costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival.

Purpose Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer. Methods and Materials Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle. The 3-fraction regimen employed a minimum of 8 Gy per fraction compared with 6 Gy for the 5-fraction regimen. Imaging was obtained every 12 weeks to assess response. Results From October 2015 to February 2017, 12 patients were enrolled in the study (median age 64; range, 55-77 years). The best response by the Response Evaluation in Solid Tumors criteria was partial response in 3 and stable disease in 3, for a disease control rate of 50%. Five patients had a grade 3 immune-related adverse event, including choreoretinitis (n = 1), pneumonitis (n = 1), transaminitis (n = 1), fatigue (n = 1), and peripheral neuropathy (n = 1). The median progression-free survival was 2.3 months, and the median overall survival was 6.9 months (range, 0.4-not reached). There was no clear association between peripheral blood T cell repertoire characteristics at baseline, PD-L1, or tumor mutations and response or outcome. One long-term survivor exhibited oligoclonal T cell populations in a baseline tumor biopsy that were consistently detected in peripheral blood over the entire course of the study. Conclusions HIGRT plus atezolizumab resulted in an overall response rate of 25% and disease control rate of 50% in this pilot study. The incidence of grade 3 adverse events was similar to that of atezolizumab alone. Alhough it was a pilot study with limited sample size, the results generated hypotheses worthy of further investigation.

Purpose: This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer (SGC). Patients and Methods: Patients with progressing incurable HN and SGC, Eastern Cooperative Oncology Group (ECOG) ≤1, no prior immunotherapy, RECIST1.1 measurable disease, and normal organ function were eligible. Pembrolizumab 200 mg was given intravenous every 21 days, and vorinostat 400 mg given orally 5 days on and 2 days off during each 21-day cycle. Primary endpoints were safety and objective response rates. Results: From November 2015 to August 2017, 25 patients with HN and 25 SGC were enrolled. Median age was 61 (range, 33–86) years, 39 (78%) were male, 21 (62%) were never smokers, and 27 (54%) had ECOG 0. In HN, 13 (52%) were p16+ oropharynx. Most common SGC histologies were adenoid cystic 12 (48%), acinic cell 3 (12%), and mucoepidermoid 3 (12%). Adverse events (AEs) in all patients were: 27 (54%) with grade ≥ 1 and 18 (36%) with grade ≥ 3. The most common AEs in all patients were renal insufficiency in seven, (14%), fatigue in six, (12%), and nausea in three (6%). There were three (12%) deaths on study. Responses in HN were complete response (CR) 0, partial response (PR) eight (32%), and stable disease (SD) five (20%). Efficacy in SGCs was CR 0, PR four (16%) in one lymphoepithelioma-like carcinoma, two acinic cell, one adenoid cystic, and SD 14 (56%). In the HN group, median follow-up (mFUP) was 12.6 months, median overall survival (mOS) was 12.6 months, and median progression-free survival (mPFS) was 4.5 months. In SGC, mFUP was 13.1 months, mOS was 14.0 months, and mPFS was 6.9 months. Conclusions: This combination demonstrated activity in HN, with fewer responses in SGC. Toxicities were higher than reported with pembrolizumab alone.

PURPOSE SEER registries do not report results of epidermal growth factor receptor ( EGFR) and anaplastic lymphoma kinase ( ALK) mutation tests. To facilitate population-based research in molecularly defined subgroups of non–small-cell lung cancer (NSCLC), we assessed the validity of natural language processing (NLP) for the ascertainment of EGFR and ALK testing from electronic pathology (e-path) reports of NSCLC cases included in two SEER registries: the Cancer Surveillance System (CSS) and the Kentucky Cancer Registry (KCR). METHODS We obtained 4,278 e-path reports from 1,634 patients who were diagnosed with stage IV nonsquamous NSCLC from September 1, 2011, to December 31, 2013, included in CSS. We used 855 CSS reports to train NLP systems for the ascertainment of EGFR and ALK test status (reported v not reported) and test results (positive v negative). We assessed sensitivity, specificity, and positive and negative predictive values in an internal validation sample of 3,423 CSS e-path reports and repeated the analysis in an external sample of 1,041 e-path reports from 565 KCR patients. Two oncologists manually reviewed all e-path reports to generate gold-standard data sets. RESULTS NLP systems yielded internal validity metrics that ranged from 0.95 to 1.00 for EGFR and ALK test status and results in CSS e-path reports. NLP showed high internal accuracy for the ascertainment of EGFR and ALK in CSS patients—F scores of 0.95 and 0.96, respectively. In the external validation analysis, NLP yielded metrics that ranged from 0.02 to 0.96 in KCR reports and F scores of 0.70 and 0.72, respectively, in KCR patients. CONCLUSION NLP is an internally valid method for the ascertainment of EGFR and ALK test information from e-path reports available in SEER registries, but future work is necessary to increase NLP external validity.

BackgroundMost patients with lung cancer are diagnosed at advanced stages. However, the advent of oral targeted therapies has improved the prognosis of many patients with lung cancer.PurposeWe aimed to understand the diagnostic experiences of patients with advanced lung cancer with oncogenic mutations.MethodsQualitative interviews were conducted with patients with advanced or metastatic non-small cell lung cancer with oncogenic alterations. Patients were recruited from online support groups within the USA. Interviews were conducted remotely or in person. Analysis used an iterative inductive and deductive process. Themes were mapped to the Model for Pathways to Treatment.Results40 patients (12 male and 28 female) with a median age of 48 were included. We identified nine distinct themes. During the ‘patient interval’, individuals became concerned about symptoms, but often attributed them to other causes. Prolonged or more severe symptoms prompted care-seeking. During the ‘primary care interval’, doctors initially treated for illnesses other than cancer. Discovery of an imaging abnormality was a turning point in diagnostic pathways. Occasionally, severity of symptoms prompted patients to seek emergency care. During the ‘secondary care interval’, obtaining tissue samples was pivotal in confirming diagnosis. Delays in accessing oncology care sometimes led to patient distress. Obtaining genetic testing was crucial in directing patients to receive targeted treatments.ConclusionsPatients experienced multiple different routes to their diagnosis. Some patients perceived delays, inefficiencies and lack of coordination, which could be distressing. Shifting the stage of diagnosis of lung cancer to optimise the impact of targeted therapies will require concerted efforts in early detection.

We investigated the association of out-of-pocket (OOP) costs for tyrosine kinase inhibitors (TKIs) with overall survival (OS) in epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-positive advanced non–small-cell lung cancer (NSCLC). We secondarily investigated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), and TKI discontinuation. METHODS: We used the Hutchinson Institute for Cancer Outcomes Research registry-claims database to identify patients with stage IV EGFR- or ALK-positive NSCLC; ≥ 1 claims for EGFR or ALK TKIs; and ≥ 3-month survival from TKI initiation. We estimated the average monthly TKI OOP costs per patient up to 3 months from TKI initiation, categorizing patients into quartiles of TKI OOP costs (Q1 < Q2 < Q3 < Q4). We conducted landmark analysis at 3 months from TKI initiation to compare Q1-3 v Q4 TKI OOP costs with respect to OS, TKI DOT, TKI adherence, and TKI discontinuation. RESULTS: Seventy-eight and twenty-seven patients comprised the Q1-3 and Q4 groups, respectively. Median monthly TKI OOP costs were $1,431 (Q1-3) v $2,888 (Q4). Compared with Q1-3, Q4 patients had inferior OS (adjusted hazard ratio [HR], 1.85; [95% CI, 1.11 to 3.10], similar TKI DOT (adjusted HR, 1.06; 95% CI, 0.53 to 2.15), decreased TKI adherence (adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76), and higher TKI discontinuation rate (adjusted OR, 8.75; 95% CI, 2.59 to 29.52). CONCLUSION: Among patients with advanced EGFR- and ALK-positive NSCLC, higher TKI OOP costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival.

BACKGROUND To better understand patient-reported quality of life (PRQOL) for patients with head and neck cancer, PRQOL scores were collected in a clinical trial. METHODS Patients were randomized to arm A (70 Gy of radiation with cisplatin) or arm B (70 Gy of radiation with cisplatin plus erlotinib at 150 mg daily). PRQOL scores were measured on days -7 (arm B only), 0, 30, and 180 with the University of Washington Quality of Life Questionnaire. Associations with clinical factors and outcomes were explored with linear mixed, logistic, and Cox regression models. RESULTS One hundred eighty-nine patients (97 in arm A and 92 in arm B) consented to PRQOL collection. Patients were balanced apart from more females in arm A (20 [21%] vs 8 [9%]; P = .02). There were 17 black patients (18%) in arm A and 12 (13%) in arm B (P = .39). There was no change in the mean scores in arm B from day -7 to day 0 (P = .36). Scores were lower in both arms at day 30 (P for both

Jorge Rios,1 Rahul Gosain,1 Bernardo HL Goulart,2 Bin Huang,3 Margaret N Oechsli,1 Jaclyn K McDowell,4 Quan Chen,4 Thomas Tucker,4 Goetz H Kloecker1 1James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 2Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, 3Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, 4Markey Cancer Center, University of Kentucky, Lexington, KY,USA Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC.Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic regression models were used to measure association between receiving treatment and comorbidity. Kaplan–Meier plots were constructed to estimate time-to-event outcomes.Results: A total of 4014 patients were identified; of this, 94.9% were white and 55.7% were male. The proportion of patients who did not receive any treatment was 8.7%, 3.9%, 19.1%, and 23.5% for stages I, II, III, and IV, respectively (p

With the promise and potential of clinical next-generation sequencing for tumor and germline testing to impact treatment and outcomes of patients with cancer, there are also risks of oversimplification, misinterpretation, and missed opportunities. These issues risk limiting clinical benefit and, at worst, perpetuating false conclusions that could lead to inappropriate treatment selection, avoidable toxicity, and harm to patients. This report presents 5 case studies illustrating challenges and opportunities in clinical next-generation sequencing interpretation and clinical application in solid tumor oncologic care. First is a case that dissects the origin of an ATM mutation as originating from a hematopoietic clone rather than the tumor. Second is a case illustrating the potential for tumor sequencing to suggest germline variants associated with a hereditary cancer syndrome. Third are 2 cases showing the potential for variant reclassification of a germline variant of uncertain significance when considered alongside family history and tumor sequencing results. Finally, we describe a case illustrating challenges with using microsatellite instability for predicting tumor response to immune checkpoint inhibitors. The common theme of the case studies is the importance of examining clinical context alongside expert review and interpretation, which together highlight an expanding role for contextual examination and multidisciplinary expert review through molecular tumor boards.

Purpose In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences. Methods and materials SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008–2011) were linked with Medicare claims (2007–2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis. Results Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p

PURPOSE Compared with single-marker genetic testing (SMGT), multigene panel sequencing (MGPS) has the potential to identify more patients with cancer who could benefit from targeted therapies, but the effects on outcome and total cost of care are uncertain. Our goal was to estimate the clinical and cost effectiveness of MGPS versus SMGT among patients with advanced non–small-cell lung cancer (aNSCLC). METHODS Patients with aNSCLC—stage IIIB or metastatic—who were diagnosed between 2011 and 2016 were identified from the Flatiron Health database. After stratifying patients into MGPS or SMGT cohorts, we analyzed the percentage of patients who received targeted treatment, survival, and total costs of care. SMGT included epidermal growth factor receptor ( EGFR) and anaplastic lymphoma kinase testing. MGPS also allowed for the detection of BRAF, RET, ROS1, HER2, and MET mutations. Cost data sources were the Centers for Medicare & Medicaid Services Fee Schedule and 2017 average sales price drug cost. We estimated the incremental cost-effectiveness ratio from a US payer perspective over a lifetime horizon using a decision model. RESULTS We identified 5,688 patients with aNSCLC who received MGPS (n = 875) or SMGT (n = 4,813), of which 22% tested positive for epidermal growth factor receptor (18.5% MGPS; 17.3% SMGT) or anaplastic lymphoma kinase (3.59% MGPS; 3.78% SMGT). Among MGPS-tested patients, an additional 8% were found to have BRAF, RET, ROS1, HER2, or MET mutations. Of MGPS-tested patients, 21% received treatments that were targeted to the specific mutations versus 19% with SMGT. Expected survival was 1.14 life years (LYs) in SMGT versus 1.20 LYs in MGPS. Lifetime total costs were $8,814 higher per patient for MGPS. The incremental cost-effectiveness ratio of MGPS versus SMGT was $148,478 per LY gained. CONCLUSION On the basis of data from a nationwide oncology patient database, MGPS is shown to have moderate cost effectiveness compared with SMGT in patients with aNSCLC.

Objectives Identify predictors of outcome in patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with weekly cetuximab and paclitaxel (CP). Study Design Retrospective analysis. Methods Patients with RMHNSCC treated with CP were identified and patient data was recorded. The Kaplan-Meier method was used to estimate outcomes, and Cox regression analysis was used to examine outcome predictors. Results Fifty-nine patients initiated CP between January 2007 and June 2014. Median age was 56 (range: 39–80) years. The most common primary sites were the oropharynx in 22 (37%) patients, oral cavity in 19 (32%), and larynx in 11 (19%). Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 in seven (12%), 1 in 32 (54%), and 2 in 16 (28%) patients. In 44 (75%) patients, CP was used as a first-line R/M regimen. Median number of cycles was five (range: 1–29). Dose modifications were necessary in 27 (46%) patients. The objective response rate was 47.5%, with 27 (45.8%) partial responses and one (2%) complete response. With a median follow-up of 13.4 months, median progression-free (PFS) and overall survival (OS) were 7.7 and 13.2 months, respectively. On multivariable analysis, an ECOG of 2 of 3 was associated with inferior OS (hazard ratio [HR]: 3.94; P = 0.01; 95% confidence interval [CI]: 1.1–14.04) and PFS (HR: 7.29; P < 0.01; 95% CI: 2.1–26.0) compared to an ECOG 0 of 1. First-line CP administration was associated with superior PFS compared to second line (HR: 2.6; P = 0.02; 95% CI:1.2–5.5). Conclusions CP is well tolerated in this population of patients, with favorable tumor efficacy. First-line use and an ECOG 0 of 1 points appears to confer superior outcomes. Level of Evidence 4. Laryngoscope, 127:1583–1588, 2017

Background Postoperative cisplatin and radiation is the standard of care for high-risk squamous cell carcinoma of the head and neck (SCCHN). We have used cetuximab and radiation in the postoperative setting for patients deemed poor candidates for cisplatin. Methods We retrospectively identified 40 patients who received cetuximab and radiation for resected locoregionally advanced SCCHN between 2006 and 2013 at our institution. Results The 2-year Kaplan–Meier estimates were: overall survival (OS) 41%, recurrence-free survival (RFS) 34%, locoregional control 63%, and distant metastatic control 59%. Eastern Cooperative Oncology Group (ECOG) performance status ≥1 predicted for inferior OS (hazard ratio [HR] = 5.43; p = .003), RFS (HR = 4.07; p = .007), and locoregional control (HR = 4.92; p = .04) in multivariate analysis. Conclusion Patients with resected high-risk SCCHN treated with postoperative cetuximab and radiation have suboptimal therapeutic outcomes. Further study of the efficacy and cost-effectiveness compared to radiation alone is warranted. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

3 Background: To assess the financial implications of therapeutic CT participation for healthcare payers, we compared first-line (1L) and second-line (2L) total direct medical costs between patients enrolled in 2L CT vs non-CT participants receiving 2L therapy for metastatic NSCLC. Methods: We linked electronic health records from a single academic center with tumor registry and claims data to identify patients with metastatic NSCLC diagnosed from 1/1/2007-12/31/2015. Eligibility criteria included 60 day minimum survival, receipt of ≥ 1 anti-cancer drug within 180 days of diagnosis, insurance enrollment for ≥ 12 months after diagnosis and receipt of ≥ 2 therapy lines. Patients on 1L trials were excluded. We calculated mean per-patient-per-month (PPPM) total direct medical costs from the payer perspective for 1L and 2L. We performed a difference-of-difference analysis to estimate the effect of trial enrollment on costs by calculating the mean PPPM difference between 2L and 1L in trial (Diff trial) and non-trial enrollees (Diff non-trial). Then we calculated the difference between Diff trial and Diff non-trial. We used paired and non-paired t-tests for statistical comparisons and report all costs in 2019 US dollars. Results: Of 63 patients, 22 (35%) enrolled in a 2L CT. CT enrollees were younger (mean age 63.5 vs 66.7 years), female (73% vs 41%), had commercial insurance (36% vs 32%), were never smokers (36% vs 32%), had EGFR mutations (27% vs 22%) and fewer had brain metastases (14% vs 29%). The mean PPPM total direct medical costs decreased between 2L and 1L for patients enrolled in 2L CTs but increased in non-trial participants (Diff trial = -$5,585, SD ± $6,541; Diff non-trial = $1,532, SD ± $14,739). The mean difference of difference (Diff trial - Diff non-trial) was -$7,117 (p = 0.01; Table). Conclusions: This small observational study suggests that CT enrollment results in substantial cost-savings to payers. If confirmed in larger studies, our findings suggest that insurers support trial participation for patients with NSCLC. [Table: see text]

9040 Background: Patients with unresectable LA-NSCLC are treated with concurrent chemoradiation (CRT) and consolidation immunotherapy with survival that range from months to years or even decades. Early predictive biomarkers have potential to identify patients who are unlikely to benefit from continuing standard of care therapy and require a change in management. We investigated biomarkers that are widely available (PET/CT scan and plasma cytokine levels) to develop early predictors (mid-CRT) of survival in a phase II clinical trial of chemoradiation for LA-NSCLC. Methods: 37 Patients with AJCC v7 stage IIB-IIIB NSCLC were prospectively enrolled on the FLARE-RT trial (NCT02773238) from 2016-9. All patients underwent chemoradiation; 18 also received adjuvant durvalumab. PET/CT exams were performed at week 3 of CRT and response status was pre-defined by published metrics. 21 patients consented to peripheral blood collection at baseline and week 3, and plasma levels of 43 common inflammatory cytokines were measured. Bootstrapping over 100 iterations of the least absolute shrinkage and selection operator (LASSO) was performed to reduce feature dimensionality and guard against false discoveries. Cox regression of selected cytokine levels and PET response status, as well as time-dependent receiver-operating characteristic (ROC) analysis, were evaluated for associations to overall survival (OS). Results: Median follow-up was 18 months with 1-year OS 81% and PFS 52%. Mid-CRT PET response (as determined by pre-defined metrics) was strongly associated with OS (HR 5.6 [1.4-22.0], p = 0.015) after adjusting for radiation target volume, with 1-yr OS 94% for responders vs. 68% for non-responders (p = 0.017). Plasma TNFα level was also prognostic for OS (HR 1.9 [1.1-3.5], p = 0.030). TNFα retained significance for OS (HR 2.3 [1.2-4.6], p = 0.016) after adjusting for PET response. Bivariate mid-CRT PET response and TNFα generated a parsimonious model to predict OS (AUC = 0.85, 18-month horizon). Conclusions: Risk stratification for long-term survival after chemoradiation in patients with LA-NSCLC may be achievable based on mid-chemoradiation assessment of widely available biomarkers (PET imaging and plasma TNFα level). Combined functional imaging and peripheral blood biomarkers will be validated in a larger sample of our trial cohort, along with other independent patient populations. Clinical trial information: NCT02773238.

7084 Background: To assess the value of CTs in advanced NSCLC from the payer perspective, we compared insurance-related total direct medical costs for NSCLC patients who enrolled in CTs vs. those who did not. Methods: After linking electronic health records with tumor registry and claims data, we identified 101 patients with metastatic NSCLC diagnosed between 1/1/2007 and 12/31/2015 and treated at the Seattle Cancer Care Alliance. Eligibility criteria included 60-day minimum survival, claims for ≥ 1 anti-cancer drug within 180 days of diagnosis and insurance enrollment for the first 12 months after diagnosis. We abstracted patient sociodemographic, disease and treatment data, and obtained death dates from the Washington State Cancer Registry, censoring patients alive on 3/7/2019.We used the Kaplan-Meier sample-average (KMSA) estimator with bootstrapped 95% confidence intervals to describe direct medical costs and compared costs in CT enrollees vs. non-enrollees by applying a generalized linear model (Gamma distribution, log link) adjusted for confounding covariates. Results: Of 101 patients, 39 (39%) enrolled in CTs. Compared with non-enrollees, CT enrollees were younger (mean age 61.6 vs. 66.5 years), female (67% vs. 47%), Asian (18% vs. 11%), never smokers (41% vs.32%), had commercial insurance (44% vs. 35%), resided in metropolitan areas (90% vs. 79%) and had a higher median income ($81,149 vs. $76,844). Table shows KMSA estimates of total direct medical costs and adjusted mean lifetime total direct medical costs by CT participation. After adjusting for sex, smoking status, residence, income, insurance payer, ECOG and mutation status, CT enrollment was associated with an increase in lifetime total direct medical costs compared with no enrollment (adjusted cost ratio=1.39; 95% CI: 1.01, 1.90; p=0.043). Conclusions: CT participation is associated with increased total direct medical costs in patients with metastatic NSCLC. Our results may inform partnerships between trial sponsors, oncology centers and payers to sustain treatment innovation through CTs. [Table: see text]

Background Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. Methods In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. Results Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18–21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18–21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). Conclusions This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. Trial registration NCT00227539 registered September 28th, 2005.

Purpose: The Centers for Medicare and Medicaid Services (CMS) recently issued a national coverage determination that provides reimbursement for low-dose computed tomography (CT) lung cancer screening for enrollees age 55 to 77 years with 30 –pack-year smoking history who currently smoke or quit in the last 15 years. The clinical, resource use, and fiscal impacts of this change in screening coverage policy remain uncertain. Methods: We developed a simulation model to forecast the 5-year health outcome impacts of the CMS low-dose CT screening policy in Medicare compared with no screening. The model used data from the National Lung Screening Trial, CMS enrollment statistics and reimbursement schedules, and peer-reviewed literature. Outcomes included counts of screening examinations, patient cases of lung cancer detected, stage distribution, and total and per-enrollee permonth fiscal impact. Results: Over 5 years, we project that low-dose CT screening will result in 10.7 million more low-dose CT scans, 52,000 more lung cancers detected, and increased overall expenditure of $6.8 billion ($2.22 per Medicare enrollee per month). The most fiscally impactful factors were the average cost–per-screening episode, proportion of enrollees eligible for screening, and cost of treating stage I lung cancer. Conclusion: Low-dose CT screening is expected to increase lung cancer diagnoses, shift stage at diagnosis toward earlier stages, and substantially increase Medicare expenditures over a 5-year time horizon. These projections can inform planning efforts by Medicare administrators, contracted health care providers, and other stakeholders.

Given the urgency to balance the delivery of high-quality cancer care with costs, stakeholders are developing new models of care delivery and reimbursement that emphasize value. The Value in Cancer Care series is a collection of 11 opinion-based articles that jointly aim to inform practicing oncologists about the pertinent facets of the value debate.

The escalating costs of cancer care have become a public health concern and a threat to the sustainability of healthcare programs. This article revises the temporal trends and major components of cancer care costs, including hospitalizations and antineoplastic drugs; provides market-based explanations for the current patterns of spending in cancer; and discusses value-based solutions that prioritize high-quality cancer care at lower costs.

BACKGROUND This study examined the microtubule inhibitor eribulin in recurrent/metastatic salivary gland cancers (RMSGCs), a disease where no therapeutic standard exists. METHODS This phase II clinical trial treated patients with progressive recurrent/metastatic salivary gland cancers with eribulin 1.4 mg/m2 i.v. on days 1 and 8 of a 21-day cycle until disease progression/unacceptable toxicities. The primary endpoint was the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 objective response rate. RESULTS Between May 2012 and August 2015, 29 patients were enrolled in this study. The median age was 63 years (range 34-75 years) and 20 of the subjects were men (69%). The most common histologies were adenoid cystic carcinoma (ACC; n = 11) and adenocarcinoma (n = 4). Neutropenia was the most common toxicity (grade 3; n = 5; 17% and grade 4 n = 3; 10%). The objective responses were observed in 3 of 29 patients (10%), 20 of 29 patients (69%) demonstrated a decrement in tumor size, and disease control was observed in 26 of 29 patients (90%). CONCLUSION Although the objective responses to eribulin were uncommon, disease control was observed in the majority of patients.

137 Background: Evidence is conflicting as to whether enrollment in therapeutic drug trials confers a survival benefit for NSCLC patients. We assessed the effect of CT participation on overall survival in a cohort of metastatic NSCLC patients treated at a single large academic center. Methods: We retrospectively revised medical records of patients with metastatic NSCLC diagnosed between 1/1/2007 and 12/31/2015 that received treatment at the Seattle Cancer Care Alliance. Eligibility criteria included receipt of ≥ 1 anti-cancer drug within 180 days of M1 diagnosis, no active second malignancy, and 60 day minimum survival. We abstracted patient sociodemographic characteristics, smoking history, ECOG score, tumor histology, EGFR and ALK status, presence of brain metastases, systemic treatment history up to 5 lines, drug trial enrollment, and trial characteristics. We obtained death dates from the Washington State cancer registry complemented by medical records, censoring patients that were alive at end of follow-up (3/7/2019). We used multivariate Cox regression to test whether enrollment in ≥ 1 CT was associated with overall survival. Results: Of 371 eligible patients (median age 63.9 years, 47% male, 94% non-squamous histology, 30% never-smokers, 58% ECOG 0-1, 20% EGFR positive and 8% ALK positive, and 27% brain metastases), 118 (32%) enrolled in ≥ 1 CT. Of CT enrollees: 19% enrolled in > 1 CT, 89% in phase I/II trials, 15% in phase III trials, 26% in randomized trials, and 51% in trials of drugs later approved by the FDA. Median survival in CT enrollees was 838 days (95% CI 688, 1,021), as compared to 454 days in non-enrollees (95% CI 378, 511). After adjusting for sex, ECOG score, smoking, histology, EGFR and ALK status, and presence of brain metastases, CT enrollees had a 47% lower risk of death relative to non-enrollees (HR 0.53; 95% CI 0.13, 0.92; P = 0.002). Conclusions: Participation in therapeutic drug trials is associated with longer overall survival in advanced NSCLC. Besides supporting drug development, CT participation may directly benefit NSCLC patients by providing access to promising agents and/or enhanced supportive care.

3 Background: Patients with EGFR+ or ALK+ NSCLC benefit from oral TKIs, but high patient OOP TKI costs could negatively impact survival by reducing likelihood of continuing TKI therapy. We assessed the association of high OOP TKI costs with overall survival (OS), medication possession ratio (MPR) and duration of TKI therapy (DOT) in patients with metastatic EGFR+ and ALK+ NSCLC. Methods: We identified patients with EGFR+ and ALK+ NSCLC diagnosed between 01/01/2010 and 12/31/2016 in the Washington State SEER registry using natural language processing, followed by manual confirmation of molecular tests. We linked registry records to commercial and Medicare (including part D) claims. Eligible patients had stage IV NSCLC, sensitizing EGFR mutations or ALK+ by FISH, ≥1 pharmacy claims for EGFR or ALK TKIs, ≥3 months survival from TKI start, and ≥12 months of insurance enrollment post diagnosis. We estimated OOP TKI costs by subtracting the amount paid from the amount allowed in pharmacy claims. We categorized patients by quartiles of monthly OOP costs calculated for the first 3 months of TKI therapy (Q1 < Q2 < Q3 < Q4). We used landmark survival analysis with multivariate Cox regression to test the association of monthly OOP costs in the first 3 months of TKIs and OS starting at 3 months of TKI therapy between Q1-Q3 vs Q4. We used t-tests to compare MPR and DOT for the 1st TKI between Q1-3 and Q4. Results: For 106 eligible patients (median age 69; 67% female; 73% White; 35% Medicare, 85% EGFR+), the median monthly OOP TKI costs at 3 months were $0 (Q1); $1,432 (Q2); $1,798 (Q3); $2,888 (Q4). Mean MPR was 1.20 vs. 1.06 (P = 0.02), and median DOT was 8 vs. 4 months (P < 0.01) for Q1-3 vs. Q4. Median OS was 22 vs. 9 months for Q1-3 vs 4. Compared with Q1-3, Q4 patients had a hazard ratio for death of 1.76 (95% CI = 1.05; 2.94; P = 0.03), adjusted for age, sex, insurance, mutation, income, chemotherapy use, and time to TKI start. There were no statistically significant associations comparing Q1 to Q2-4, or Q1-2 to Q3-4. Conclusions: Higher patient OOP TKI costs are associated with lower number of TKI prescriptions, shorter duration of TKI therapy and inferior survival in advanced EGFR+ and ALK+ NSCLC.

134 Background: Molecular testing practices and cost-sharing policies may result in delayed initiation of TKI therapy. We assessed predictors of delayed initiation of TKIs in metastatic EGFR+ or ALK+ NSCLC. Methods: We identified patients with EGFR+ and ALK+ NSCLC diagnosed between 01/01/2010 and 12/31/2016 in the Washington State SEER registry using validated natural language processing methods. We linked registry records to commercial and Medicare (including part D) claims. Eligible patients had stage IV NSCLC, sensitizing EGFR mutations or ALK+ by FISH, ≥ 1 pharmacy claims for EGFR or ALK TKIs, and ≥12 months of insurance enrollment post-diagnosis. Potential predictors included age, sex, race, Census-level median household income, urban status, insurance type, comorbidity, histology, mutation type, and receipt of chemotherapy prior to first TKI claim (pre-TKI chemo). We defined time to TKI initiation as the interval from diagnosis to first pharmacy claim for EGFR or ALK TKIs. We fitted Cox regression models to identify predictors of delays in TKI initiation, defining covariates with a P < 0.05 in a final multivariate model as independently associated with delays. Results: For 122 patients (median age 70; 65% female; 74% White; median income $66,580; 98% metropolitan; 35% Medicare; 80% EGFR+; 12% using pre-TKI chemo), the median time to TKI initiation was 6.7 weeks (IQR = 3.9 to 14.0). Independent predictors of TKI delays included male sex (HR = 0.51; 95%CI = 0.34; 0.76); Medicare insurance (HR = 0.32; 95% CI = 0.20; 0.53) and pre-TKI chemo (HR = 0.37; 95% CI = 0.20; 0.66). Median time to TKI initiation was 9.7 vs. 5.8; 7.8 vs. 4.1; and 16.0 vs. 6.3 weeks in male vs. female, Medicare vs. commercial insurance, and pre-TKI chemo (yes vs no), respectively. Conclusions: Male sex, Medicare insurance, and chemotherapy prior to TKI are associated with delays in TKI initiation for EGFR+ and ALK+ stage IV NSCLC patients. Possible explanations include higher prevalence of smoking in males resulting in lower priority for molecular testing, high cost-sharing policies for TKIs in Medicare patients, and prolonged time to obtain molecular test results leading patients to start chemotherapy first.

Comparative effectiveness research (CER) has emerged as an approach to improve quality of care and patient outcomes while reducing healthcare costs by providing evidence to guide healthcare decisions. Randomized controlled trials (RCTs) have represented the ideal study design to support treatment decisions in head-and-neck (HN) cancers. In RCTs, formal chance (randomization) determines treatment allocation, which prevents selection bias from distorting the measure of treatment effects. Despite this advantage, only a minority of patients qualify for inclusion in HN RCTs, which limits the validity of their results to the broader HN cancer patient population seen in clinical practice. Randomized controlled trials often do not address other knowledge gaps in the management of HN cancer, including treatment comparisons for rare types of HN cancers, monitoring of rare or late toxicity events (eg, osteoradionecrosis), or in some instances an RCT is simply not feasible. Observational studies, or studies in which treatment allocation occurs independently of investigators' choice or randomization, may address several of these gaps in knowledge, thereby complementing the role of RCTs. This critical review discusses how observational CER studies complement RCTs in generating the evidence to inform healthcare decisions and improve the quality of care and outcomes of HN cancer patients. Review topics include a balanced discussion about the strengths and limitations of both RCT and observational CER study designs; a brief description of design and analytic techniques to handle selection bias in observational studies; examples of observational studies that inform current clinical practices and management of HN cancers; and suggestions for relevant CER questions that could be addressed by an observational study design.

The National Lung Screening Trial (NLST) has sparked new interest in the adoption of lung cancer screening using low-dose computed tomography (LDCT). If adopted at a national level, LDCT screening may prevent approximately 18,000 lung cancer deaths per year, potentially constituting a high-value public health intervention. Before incorporating LDCT screening into practice, health care institutions need to consider the risks associated with LDCT screening and the impact of LDCT screening on health care costs, as well as other remaining areas of uncertainty, including the unknown cost-effectiveness of LDCT screening. This article will review the benefits and risks of LDCT screening in light of the results of the NLST and other randomized trials, it will discuss the additional health care costs associated with LDCT screening from the perspective of health care payers, and it will examine the published cost-effectiveness analyses of LDCT screening. A subsequent discussion highlights guideline recommendations for implementation strategies, the goals of which are to ensure that those eligible for LDCT screening derive the benefits while minimizing the risks of screening and avoiding an unnecessary escalation in screening-related costs. The article concludes by endorsing the use of LDCT screening in institutions capable of responsible implementation of screening in both medical and economic terms. The key elements of responsible implementation include the development of standardized screening practices, careful selection of screening candidates, and the creation of prospective registries that will mitigate current areas of uncertainty regarding LDCT screening.

Little is known about how referrals to different cancer specialists influence cancer care for non-small-cell lung cancer (NSCLC). Among Medicare enrollees, we identified factors of patients and their primary care physician that were associated with referrals to cancer specialists, and how the types of cancer specialists seen correlated with delivery of guideline-based therapies (GBTs).Data from patients with stages III and IV NSCLC included in the SEER-Medicare database were linked to their physicians in the American Medical Association Masterfile database. Using logistic regression, we (1) identified patient and physician factors that were associated with referrals to cancer specialists (medical oncologists, radiation oncologists, and surgeons); (2) identified the types of referral to cancer specialists that predicted greater likelihood of receiving GBT (per National Comprehensive Cancer Network guidelines).A total of 28,977 patients with NSCLC diagnosed from January 1, 2000 to December 31, 2005 met eligibility criteria. Younger age, white race, higher income, and primary physician specialty other than family practice predicted higher likelihood of referrals to medical oncologists (P.01 for all predictors). Seeing the three types of cancer specialists predicted higher likelihood of GBT (stage IIIA: odds ratio [OR] = 20.6; P.001; IIIB: OR = 77.2; P.001; and IV: OR = 1.2; P = .011), compared with seeing a medical oncologist only. Use of GBTs increased over the study period (42% to 48% from 2000 to 2005; P.001).Referrals to all types of cancer specialists increased the likelihood of treatment with standard therapies, particularly in stage III patients. However, racial and income disparities still prevent optimal referrals to cancer specialists.

Purpose: As Toll-like receptors (TLR) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy of therapies for squamous cell carcinoma of the head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes. A phase Ib clinical trial assessed the safety and antitumor activity of motolimod in combination with cetuximab in patients with SCCHN. Correlative biomarkers of immune activity were explored. Experimental Design: Thirteen patients with recurrent or metastatic SCCHN were enrolled in this open-label, dose–escalation study using a standard 3 + 3 design. Doses of motolimod (2.5, 3.0, or 3.5 mg/m2) were given on days 1, 8, and 15, in combination with fixed weekly doses of cetuximab in 28-day cycles. Results: There were no protocol-defined dose-limiting toxicities, drug-related deaths, or evidence of synergistic toxicities between motolimod and cetuximab. Clinical tolerability at the 3.5 mg/m2 dose level was not optimal for repeated dosing and 3.0 mg/m2 was identified as the MTD. Two patients achieved partial responses for an overall response rate of 15%. Five patients had disease stabilization equating to a disease control rate of 54%. Statistically significant increases in plasma cytokines and in the frequency and activation of circulating NK cells were observed. Conclusions: Motolimod can be safely administered in combination with cetuximab with an acceptable toxicity profile. Encouraging antitumor activity and robust pharmacodynamic responses were observed. Motolimod is being further investigated in a phase II trial in patients with SCCHN (ClinicalTrials.gov ID: NCT01836029). Clin Cancer Res; 23(10); 2442–50. ©2016 AACR.

Background Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients. Materials and methods We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990-2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use. Results From 1990-2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively. Conclusion Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:304-310 IMPLICATIONS FOR PRACTICE: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990-2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.

A recent randomized trial showed that low-dose CT (LDCT) screening reduces lung cancer mortality. Health care providers need an assessment of the national budget impact and cost-effectiveness of LDCT screening before this intervention is adopted in practice. Using data from the 2009 National Health Interview Survey, CMS, and the National Lung Screening Trial (NLST), the authors performed an economic analysis of LDCT screening that includes a budget impact model, an estimate of additional costs per lung cancer death avoided attributed to screening, and a literature search of cost-effectiveness analyses of LDCT screening. They conducted a one-way sensitivity analysis, reporting expenditures in 2011 U.S. dollars, and took the health care payer and patient perspectives. LDCT screening will add $1.3 to $2.0 billion in annual national health care expenditures for screening uptake rates of 50% to 75%, respectively. However, LDCT screening will avoid up to 8100 premature lung cancer deaths at a 75% screening rate. The prevalence of smokers who qualify for screening, screening uptake rates, and cost of LDCT scan were the most influential parameters on health care expenditures. The additional cost of screening to avoid one lung cancer death is $240,000. Previous cost-effectiveness analyses have not conclusively shown that LDCT is cost-effective. LDCT screening may add substantially to the national health care expenditures. Although LDCT screening can avoid more than 8000 lung cancer deaths per year, a cost-effectiveness analysis of the NLST will be critical to determine the value of this intervention and to guide decisions about its adoption.

6513Background: MGPS, compared to single-marker genetic testing (SMGT), has the potential to identify more patients who could benefit from targeted therapies, but the impact on outcomes and total c...

6612Background: In May of 2017, the U.S. FDA granted accelerated approval for pembrolizumab + pemetrexed & carboplatin for previously untreated advanced non-squamous NSCLC—the only first-line indic...

6025Background: Epigenetic modification is increasingly recognized as a mechanism for tumor immune evasion. This clinical trial explored the activity of P with the HDAC inhibitor V in HN and SGC. M...

e17506 Background: The anti-PD1/-PDL1 ICmABs can result in objective responses in some (13-20%) patients (pts) with HNSCC. We evaluated clinical factors that may predict oncologic outcomes. Methods: We identified pts who received an ICmAB at our institution and retrospectively collected demographic, tumor, treatment, progression, and survival data. The Kaplan Meier method was used to estimate survival. Log-rank and Wilcoxon tests were used to explore associations between clinical features and outcomes. Results: 55 pts received ICmAB in a clinical trial at our center from 8/2012 to 12/2016. The median age was 64 years, 13 (24%) were female, and 45 (82%) were white. ECOG Performance Status (PS) was 0 and 1 in 23 (42%) and 32 (58%) pts, respectively. 29 (53%) were current/former smokers who smoked a median of 20 (range 0-70) pack years. Primary sites included: oropharynx (OP) 31 (56%), oral cavity 9 (16%), nasopharynx 6 (11%), nasal cavity 3 (5%), hypopharynx (HP) 2 (4%), unknown (UK) 2 (4%), and skin 2 (4%). 28 (51%) were p16+, with the following primary sites: OP in 26, UK in 1, and HP in 1. 53 (96%) received prior curative intent therapy. A median of 2 (range 0-5) lines of systemic therapy (including curative intent) were given prior to ICmAB initiation, and 31 received an ICmAB as a single agent. There were 19 (35%) objective responses with 1 complete response, and 14 (25%) had stable disease. With a median follow-up of 12 months (m), the median overall survival (OS) was 15m (95% CI 11,47), and median time to progression was 4m (95% CI 2.2, 6.8). An ECOG PS of 0 vs 1 was associated with superior OS (36m vs 11m p = 0.001). Tobacco use, p16+ disease, single agent ICmAB vs. combination, number of lines of prior systemic therapy, or radiation therapy within 3m prior to ICmAB initiation did not appear to have a relationship with survival. Conclusions: A PS of 0 predicted for more favorable OS among HNSCC pts receiving ICmAB in this single center retrospective cohort. In contrast to data with chemotherapy, established prognostic markers (including p16+ and limited/no tobacco use) did not appear to impact survival.

6528 Background: The Surveillance, Epidemiology, and End Results (SEER) registries lack information on the Epidermal Growth Factor Receptor (EGFR) mutation and Anaplastic Lymphoma Kinase (ALK) gene rearrangement test results. With the goal of enabling population-based outcomes research in molecularly selected NSCLC subgroups, we conducted a validation study of NLP for ascertainment of EGFR and ALK testing from electronic pathology reports (e-paths) of patients included in the Seattle-Puget Sound (SPS) and Kentucky Cancer (KCR) SEER registries. Methods: We obtained 4,278 and 1,041 e-paths pertaining to 1,634 and 565 patients with stage IV non-squamous NSCLC diagnosed from 1/1/2011 to 12/31/2013 and included in the SPS and KCR registries, respectively. Two oncologists independently reviewed all reports to generate a gold-standard dataset. We used 855 of the SPS reports to train hybrid rule-based and machine learning algorithms for detection of test status (reported vs. not reported), and test result if reported (positive vs negative) for EGFR mutational analysis and ALK testing by FISH, IHC, or gene sequencing. In the remaining 3,423 SPS reports, we conducted a 5-fold cross-validation analysis to estimate the internal NLP sensitivity, specificity, positive predictive value, and negative predictive value for test status and results, respectively. We used a hierarchical rules system to assess the NLP accuracy at the patient level. For external validation, we repeated all analyses in the KCR dataset. Results: In the SPS internal validation report sample, the validity metrics ranged from 97% to 99% for EGFR and ALK test status, and from 95% to 100% for EGFR and ALK test results, respectively. In the KCR external validation report sample, the metrics ranged from 74% to 96% for EGFR and ALK test status, and 2% to 100% for test results, respectively. At the patient level, the NLP accuracy for EGFR and ALK was 95% and 96% (SPS cohort), and 70% and 72% (KCR cohort) respectively. Conclusions: NLP is a valid method for determining EGFR and ALK test status and results for patients included in SEER registries with access to e-path, but the algorithms likely need to be registry-specific.

240 Background: The American Society for Radiation Oncology (ASTRO) ‘Choosing Wisely’ (CW) list notes radiation interventions lacking evidence of benefit in cancer care. This study characterizes adherence to the 2014 CW item to ‘not recommend radiation following hysterectomy in low-risk endometrial cancer’ (Stage I, Grade 1-2). No studies have previously evaluated adherence to this CW item. Methods: SEER records for patients age >65 at first primary diagnosis of Stage I (Grade 1-2) endometrial cancer between 2008-2011 were linked with Medicare files. Included cases had Medicare Part A and B coverage for ≥12 months before/after diagnosis and had a hysterectomy 1 month prior to 4 months following diagnosis. We used logistic regression to evaluate associations between socio-demographic and clinical characteristics (Table 1) and receipt of radiation therapy within 1 year of diagnosis. Results: Among 2,938 women meeting eligibility criteria, mean age was 74, 90% were white, and 55% lived in a ‘big metro’ area (population >1m). The non-adherent fraction was 24%. Among non-adherent cases, 76% received brachytherapy. In adjusted analyses (Table 1), only tumor grade was associated with non-adherence. Conclusions: More than 20% of low-risk endometrial cancer cases in our sample were non-adherent to ASTRO CW recommendations, and this only varied significantly by tumor grade. Therefore, use of radiation therapy following hysterectomy appears to be a widespread issue. This is important because non-adherence may result in side effects or substantial cost without commensurate clinical benefit. This study’s follow-up period was prior to the ASTRO CW list, but similar recommendations existed in ASCO, ESMO and NCCN guidelines at the time—suggesting work is need to align practice with guidelines. Our findings provide a baseline measure against which future studies can measure progress. [Table: see text]