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Background: High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC)., Methods: We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods., Results: Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86-1.09), ETFS (HR 1.05; 95% CI 0.93-1.18), CSS (HR 0.94; 95% CI 0.84-1.04), or OS (HR 0.95; 95% CI 0.87-1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively., Conclusion: hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial., Competing Interests: Dr. Wang reports personal fees and non-financial support from AbbVie, non-financial support from Merck, personal fees from AstraZeneca, personal fees from Doximity, personal fees and non-financial support from Novocure, personal fees and nonfinancial support from Elekta and personal fees from Wolters Kluwer, outside the submitted work; Dr. Cheng reports consulting fees from AbbVie. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have no conflicts of interest.

Objectives: Women with lung cancer have better survival than men. The reasons are unknown, but estrogen is hypothesized to improve survival. Our objective was to examine the association between estrogen monotherapy and cancer-specific and overall survival in elderly women with non-small cell lung cancer (NSCLC)., Materials and Methods: We used the SEER-Medicare database to identify women ≥65 years old who were diagnosed with stage III or IV NSCLC. Estrogen monotherapy (EM) was defined as at least one estrogen claim without any progesterone claims 6 months prior to diagnosis. To assess cancer-specific survival and overall survival, we used Kaplan-Meier and multivariate Cox modeling with propensity score adjustments. As an exploratory analysis, we also examined the effect of combined estrogen and progesterone hormonal therapy on survival using Cox modeling., Results: We identified 6958 women in our initial cohort: 283 used EM (4%) and 6675 (96%) did not. The median follow-up time was 46.5 months in the EM patients and 49.5 months in the non-EM patients. In a Kaplan-Meier analysis, median overall survival was 8.2 months in patients who receive EM and 6.2 months in those who did not (p = 0.004). In our 1:4 propensity-matched cohort, median follow-up was 46.5 in the EM group and 50.6 in the non-EM group; median overall survival was 8.0 months in the EM group and 6.4 months in the non-EM group (p = 0.02). In a multivariate Cox regression of the matched cohort, EM was significantly associated with overall survival (HR 0.84; 95% CI 0.73 - 0.97). All results were similar for cancer-specific survival. In our exploratory analysis, combined Estrogen-Progesterone did significantly impact overall survival (HR 0.84; 95% CI 0.71-0.99, p = 0.04) but did not appear to effect cancer-specific survival (HR 0.91; 95% CI 0.77-1.09, p = 0.30)., Conclusion: EM was associated with a significant improvement in cancer-specific survival and overall survival in women with late stage NSCLC., (Copyright © 2019. Published by Elsevier B.V.)

Background: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients., Patients and Methods: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression., Results: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes., Conclusions: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: A subset of patients with minimal extrathoracic disease may benefit from aggressive primary tumor treatment. We report comparative outcomes in oligometastatic non-small cell lung cancer (NSCLC) treated with and without definitive, conventionally fractionated thoracic radiation therapy., Methods and Materials: We identified consecutive patients with stage IV NSCLC who had an Eastern Cooperative Oncology Group performance status ≤2 and ≤4 total sites of metastatic disease and who had been prescribed ≥50 Gy of thoracic radiation., Results: Twenty-nine patients with oligometastatic NSCLC were identified between January 2004 and August 2010. Median survival was 22 months from diagnosis. Four patients (14%) experienced pneumonitis greater than or equal to grade 3; 6 (21%) had esophagitis greater than or equal to grade 3. Local control was associated with improved survival (P = .02). In matched subset analysis, median survival was 9 months (P < .01) in patients who received chemotherapy alone. Median time to local failure was 18 versus 6 months (P = .01). On multivariable analysis, radiation (P < .01; odds ratio [OR], 0.33), fewer metastases (P < .01; OR, 2.14), and female sex (P < .01; OR, 0.41) were associated with improved survival., Conclusions: Definitive dose radiation therapy may improve survival in a select subset of patients with minimal extrathoracic disease in whom local progression is of primary concern. Prospective trials are needed to further evaluate the role of local control in oligometastatic NSCLC., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: This study examined rates of tumor progression in treatment-naive patients with non-small-cell lung cancer (NSCLC) as determined by repeat treatment-planning fluorine-18 ((18)F) fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT)., Methods and Materials: This study assessed patients who underwent PET/CT simulation for NSCLC stage II/III, radiation-naive, nonmetastatic NSCLC. It compared planning PET/CT with previous PET/CT images. Patients were analyzed for change in stage, treatment intent, or both. Progression was defined as a change in TNM status leading to upstaging, and standardized uptake value (SUV) velocity was defined as [(SUVscan2 - SUVscan1)/interscan interval in days]., Results: Of 149 consecutive patients examined between April 2009 and April 2011, 47 had prior PET/CT scans and were included. The median age was 68 years. New nodal disease or metastatic disease was identified in 24 (51%) of 47 patients. Fourteen (30%) had evidence of extrathoracic metastatic disease; the remaining 10 (21%) had new nodal disease that required substantial alteration of treatment fields. At a scan interval of 20 days, the rate of upstaging was 17%. SUV velocity was analyzed in the subset of patients who had their studies on the identical PET/CT scanner (n = 14). Nonupstaged patients had a mean SUV velocity of 0.074 units per day, compared with 0.11 units per day in patients that were upstaged by their second PET/CT scan (P = .020)., Conclusion: Radiation treatment planning with hybrid PET/CT scans repeated within 120 days of an initial staging PET/CT scan identified significant upstaging in more than half of patients. For a subset of patients who underwent both scans on the same instrument, SUV velocity predicts upstaging, and the difference between those upstaged and those not was statistically significant., (Copyright © 2014 Elsevier Inc. All rights reserved.)