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Introduction: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States., Materials and Methods: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression., Results: A total number of 54,922 Veterans were identified with lung cancer diagnosed from 2010 to 2017. Histologies were classified as non-small-cell lung cancer (NSCLC) (64.2%), small cell lung cancer (SCLC) (12.9%), and 'other' (22.9%). The proportion with stage I increased from 18.1% to 30.4%, while stage IV decreased from 38.9% to 34.6% (both P < .001). The 3-year overall survival (OS) improved for stage I (58.6% to 68.4%, P < .001), stage II (35.5% to 48.4%, P < .001), stage III (18.7% to 29.4%, P < .001), and stage IV (3.4% to 7.8%, P < .001). For NSCLC, the median OS increased from 12 to 21 months (P < .001), and the 3-year OS increased from 24.1% to 38.3% (P < .001). For SCLC, the median OS remained unchanged (8 to 9 months, P = .10), while the 3-year OS increased from 9.1% to 12.3% (P = .014). Compared to White Veterans, Black Veterans with NSCLC had similar OS (P = .81), and those with SCLC had higher OS (P = .003)., Conclusion: Lung cancer survival is improving within the VHA. Compared to White Veterans, Black Veterans had similar or higher survival rates. The observed racial equity in outcomes within a geographically and socioeconomically diverse population warrants further investigation to better understand and replicate this achievement in other healthcare systems., Competing Interests: Disclosure DM is a consultant and/or advisor for AstraZeneca, Delfi Diagnostics, Viewray, and Merck; is a scientific advisor for Lungevity Foundation and GO2 Foundation for Lung Cancer; is co-director of the VA Greater Los Angeles Lung Precision Oncology Program; is on the scientific advisory board and owns stock options in Lung Life AI. DG is a founder of SwitchboardMD, is on the advisory board of Histowiz LLC, and owns stock in PortalBurner LLC, Histowiz LLC, and SwitchboardMD. JL is a board member of Rescue Lung Rescue Life and is Co-director of the Tennessee Valley Healthcare System Lung Cancer Screening Program. LS is a member of the Tennessee Valley Healthcare System Lung Cancer Screening Steering Committee and Vice Chair of Health Equity at Vanderbilt University Medical Center Radiology. CS is a Medical Director of the VAPORHCS lung nodule surveillance system, Director for the VISN 20 Centralized Lung Cancer Screening Program, and Chief Consultant for the VA National Center for Lung Cancer Screening. He does not receive additional remuneration for this role. He has a grant from the Oregon Health and Science University Knight Cancer Institute (KCI) to develop a nodule/lung cancer risk prediction model that includes working with a for-profit company, Optellum, Ltd. Neither he nor the KCI receive remuneration for this collaboration. All other authors declare no conflicts of interest., (Published by Elsevier Inc.)

Purpose: Emerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity-modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution., Materials and Methods: Data were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et al (PMID: 34944813) and Ladbury et al's (PMID: 31175902) models were abstracted. Paired t tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans., Results: IMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE vs 4.99 Gy, P  < .001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE vs 7.60 Gy, P  < .002). Modeled 2-year overall survival was significantly longer with IMPT than IMRT (median 71% vs 63%; P  = .03)., Conclusion: IMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC., (© 2024 The Author(s).)

Background: Immune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications., Patients and Methods: In this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI., Results: We identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001)., Conclusion: This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated., Competing Interests: Disclosure NTS has no disclosures. WAS has no disclosures. MB has no disclosures. RJ has no disclosures. DAG has no disclosures. ZH has no disclosures. AB has no disclosures. VS has no disclosures. MCL has no disclosures. SSR has received grant funding and/or other support (for consultancy) from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, Takeda, Tesaro, Advaxis, AbbVie, and Genentech/Roche. VPS is on the SAB of BERG and HiFiBio Therapeutics, and an equity holder in Aggamin Pharmaceuticals and Victa Biotherapeutics. DM has received travel support and speaking honoraria from Varian Medical Systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Locoregional recurrence remains common after treatment of head and neck cancer, warranting careful surveillance in follow-up. Although randomized data support an initial positron emission tomography/computed tomography several months after treatment, evidence supporting subsequent imaging is limited, and most recurrences ultimately manifest clinically. Cooperative group studies and consensus guidelines vary widely in their recommendations regarding surveillance imaging. Patients with indeterminate findings, new symptoms, or areas difficult to examine in clinic may avoid invasive and potentially morbid interventions with judicious use of subsequent imaging. For any patient undergoing posttreatment imaging, standardized reporting criteria provide a framework for risk-stratification that can enhance communication and potentially guide management., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Operability is both a crucial determinant in treatment selection and a potential confounder in analyses comparing surgery with non-surgical approaches such as stereotactic body radiotherapy (SBRT). We aimed to assess the association between operability status and intervention with post-treatment mortality in early-stage non-small cell lung cancer (NSCLC)., Patients and Methods: We defined four groups of patients with cT1-T2N0M0 NSCLC diagnosed 2010 to 2014 from the National Cancer Database: SBRT patients deemed operable vs. inoperable and surgery patients receiving open vs. minimally-invasive approaches. Mortality rates at 30, 60, and 90 days post-treatment were calculated and compared., Results: We abstracted 80,108 patients, 0.8% undergoing SBRT and operable, 13.2% undergoing SBRT and inoperable, 52.4% undergoing open surgery, and 33.7% undergoing minimally-invasive surgery. Mortality rates were highest among open surgery patients and lowest among operable SBRT patients (2.0% vs. 0.2% at 30 days and 3.7% vs. 0.7% at 90 days), with intermediate results in the other two groups. These findings persisted on multivariate Cox regression: compared to patients undergoing minimally-invasive surgery, mortality risk was highest among open surgery patients (30 days HR 1.32, 95%CI 1.16-1.51; 90 days HR 1.36, 95%CI 1.24-1.50; both P < .001) and lowest among operable SBRT patients (30 days HR 0.09, 95%CI 0.01-0.64; 90 days HR 0.15, 95%CI 0.05-0.46; both P ≤ .016). These associations were maintained in a propensity score-matched subset., Conclusion: Operable patients undergoing SBRT experience minimal post-treatment mortality compared to their inoperable counterparts. These findings illustrate the potential for confounding by operability to bias results in cohort studies that compare surgical vs. non-surgical approaches in early-stage NSCLC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Recent preclinical research has renewed interest in the interplay between glucose dysregulation and cancer. Metformin holds promise as an adjunctive antineoplastic agent in head and neck cancer (HNC). We aimed to explore the impact of metformin in HNC patients from a population-based dataset., Patients & Methods: Patients diagnosed with HNC from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset and categorized into three groups: non-diabetics (nD), diabetics not taking metformin (DnM), and diabetics taking metformin (D + M). Overall survival (OS) and cancer-specific survival (CSS) were compared between groups using Kaplan-Meier and Cox regression controlling for sociodemographic, clinical, and treatment covariates. The incidence of toxicities associated with HNC therapy was compared among groups using χ 2 analysis., Results: Among 1646 patients, there were 1144 nD, 378 DnM, and 124 D + M. 2-year OS rates was 65.6% for nD, 57.7% for DnM, and 73.4% for D + M by Kaplan-Meier (p < 0.01), and corresponding rates of 2-year CSS were 73.7%, 66.1%, and 88.8% (p < 0.01), respectively. On Cox multivariable analysis, OS among the three groups did not significantly differ; however, CSS was significantly worse among both nD versus DnM as compared to D + M. Toxicity rates were not significantly increased among D + M., Conclusion: HNC patients with diabetes taking metformin experience improved CSS. Prospective investigation of the addition of metformin to standard-of-care HNC therapy is warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making., Methods: Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM., Results: 5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p < 0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T-classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61 and HPV- 11.66, p = 0.17)., Conclusions: These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: While the roles of hypofractionated (HFxn) radiotherapy and lumpectomy boost in the adjuvant management of invasive breast cancer are supported by the results of clinical trials, randomized data supporting their use for ductal carcinoma in situ (DCIS) are forthcoming. We sought to evaluate current national trends and identify factors associated with HFxn and boost usage using the National Cancer Database., Patients and Methods: We queried the National Cancer Database for women diagnosed with DCIS from 2004 to 2014 undergoing external beam radiotherapy after breast conservation surgery. Patients were categorized as receiving either conventional fractionation (CFxn) or HFxn and as either receiving or not receiving a boost. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations., Results: A total of 101,615 women were identified, with 87,641 (86.2%) receiving CFxn, 13,974 (13.8%) receiving HFxn, and most patients in each group (84.9% and 57.7%, respectively) receiving a boost. Implementation of HFxn increased from 4.3% in 2004 to 33.0% in 2014, and the use of a boost declined from 83.3% to 74.6%. HFxn receipt was independently associated with later year of diagnosis, older age, higher income, greater distance from treatment facility, greater facility volume, academic facility type, Western residence, smaller lesions, and nonreceipt of a boost. Factors associated with boost receipt included earlier year of diagnosis, younger age, higher income, community facility type, adverse pathologic features, and nonreceipt of HFxn., Conclusion: Although CFxn with a boost remains the most common external beam radiotherapy strategy for DCIS, implementation of HFxn without a boost appears to be increasing. Practice patterns at present seem to be driven by guidelines for invasive breast cancer and nonclinical factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Among patients with T2N0M0 glottic larynx cancer undergoing definitive radiotherapy, recent retrospective and prospective data have suggested improved outcomes with altered fractionation over conventional fractionation (CFxn). We sought to characterize national fractionation patterns and to compare outcomes among them., Materials and Methods: We queried the National Cancer Database for T2N0M0 squamous cell carcinomas of the glottis diagnosed from 2004-2014 and managed with definitive radiotherapy. Dose-per-fraction and duration of radiotherapy were used to define cohorts undergoing CFxn, hypofractionation (HypoFxn), and hyperfractionation (HyperFxn). Logistic regression was performed to identify predictors of receiving altered fractionation. Cox regression and propensity-score matching (PSM) analyses were used to compare survival between schedules., Results: We abstracted 2 006 CFxn patients, 1 166 HypoFxn patients, and 161 HyperFxn patients. Fractionation patterns changed significantly from 2004 to 2014, with use of HyperFxn decreasing from 6.3% to 1.8% and use of HypoFxn increasing from 23.9% to 54.1% (p<0.001). Receipt of altered fractionation was independently associated with later year of diagnosis and higher facility volume. On Cox regression, both HypoFxn (hazard ratio [HR] for mortality 0.84, 95% confidence interval [95%CI] 0.73-0.97) and HyperFxn (HR 0.74, 95%CI 0.56-0.99) were associated with improved survival over CFxn. The survival advantage of each altered fractionation schedule over CFxn was redemonstrated on comparison of PSM groups., Conclusion: Increasing utilization of HypoFxn for T2N0M0 glottic cancer is driving national practice patterns away from CFxn. Our findings support the use of altered fractionation, particularly HypoFxn, for patients undergoing definitive radiotherapy, although HyperFxn remains understudied in a prospective fashion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Preclinical and clinical research over the past several decades suggests that hypofractionated (HFxn) radiation therapy schedules produce similar treatment outcomes compared with conventionally fractionated (CFxn) radiation therapy for definitive treatment of localized prostate cancer (PCa). We sought to evaluate national trends and identify factors associated with HFxn utilization using the US National Cancer Database., Methods and Materials: We queried the National Cancer Database for men diagnosed with localized (N0,M0) PCa from 2004 through 2013 treated with external beam radiation therapy. Patients were grouped by dose per fraction (DpF) in Gray: CFxn was defined as DpF ≤2.0, moderate HFxn as DpF >2.0 but <5.0, and extreme HFxn as DpF ≥5.0. Men receiving DpF <1.5 or >15.0 were excluded, as were those receiving <25 or >90 Gy total dose. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations., Results: A total of 132,403 men were identified, with 120,055 receiving CFxn, 7264 moderate HFxn, and 5084 extreme HFxn. Although CFxn was by far the most common approach over the analysis period, HFxn use increased from 6.2% in 2004 to 14.2% in 2013 (P < .01). Extreme HFxn use increased the most (from 0.3% to 8.5%), whereas moderate HFxn utilization was unchanged (from 5.9% to 5.7%). HFxn use was independently associated with younger age, later year of diagnosis, non-black race, non-Medicaid insurance, non-Western residence, higher income, academic treatment facility, greater distance from treatment facility, low-risk disease group (by National Comprehensive Cancer Network criteria), and nonreceipt of hormone therapy., Conclusions: Although CFxn remains the most common radiation therapy schedule for localized PCa, use of HFxn appears to be increasing in the United States as a result of increased extreme HFxn use. Financial and logistical factors may accelerate adoption of shorter schedules. Considering the multiple demographic and prognostic differences identified between these groups, randomized outcome data comparing extreme HFxn to alternatives are desirable., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Though the effect of age has been studied in some cancer types, its prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. Our purpose is to determine the impact of age at diagnosis on overall survival (OS) and disease-specific survival (DSS) in patients with OPSCC. If the effect is significant, we aim to clarify the age at which prognosis worsens., Materials and Methods: 15,978 Patients with OPSCC were identified from the Surveillance, Epidemiology, and End Results (SEER) database and separated into 10 year age groups. We obtained data on age at diagnosis, primary location, race, stage, sex, radiological treatment status, and surgical treatment status. Kaplan-Meier methods were used to calculate the OS and DSS for each age group. DSS analysis was supported by a Simple Multivariable Cox Proportional Hazard Regression of all significant variables studied., Results: Significant disadvantage in OS and DSS was found with increasing age. A three-group stratification was depicted with the best survival in patients aged 1-44, mildly inferior survival in patients aged 45-64, and increasingly worse survival in patients 65 and older. Multivariable analysis demonstrated statistically significant increases in hazard ratio (HR) after age 65 when compared to ages 1-64., Conclusion: Increasing age after 65 is associated with worsening OS and DSS in OPSCC. Poorer prognosis is due to multiple factors, possibly including the effects of aging, which make elderly patients more susceptible to the pathogenesis of OPSCC., (Copyright © 2014 Elsevier Ltd. All rights reserved.)