Date of Award

January 2022

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Henry S. Park

Second Advisor

Shari Damast


Hypofractionated radiotherapy (HFRT) is more convenient, less expensive, and decreases healthcare exposure during the Coronovirus-19 pandemic compared to conventional fractionation (CFRT). HFRT is preferred in many Western countries for limited-stage small cell lung cancer (LS-SCLC) but not used regularly in the U.S. Additionally, the impact of HFRT in unresected stage I non-small cell lung cancer (NSCLC) unsuitable for stereotactic body radiation therapy (SBRT) is unclear. We examined practice patterns and overall survival (OS) associated with definitive HFRT in both these settings. We conducted two separate retrospective cohort analyses using the National Cancer Database: (1) patients with unresected primary stage II-III LS-SCLC who underwent chemotherapy within six months of either HFRT or standard radiation (RT), and (2) patients with unresected stage I NSCLC who underwent CFRT, low-dose HFRT (LD-HFRT), or high-dose HFRT (HD-HFRT) without systemic therapy. Patient characteristics were evaluated using chi-square analysis and logistic regression. We used Kaplan-Meier estimator, log-rank test, and Cox regression to assess OS. In our LS-SCLC study, we performed subset analyses to determine the impact of chemotherapy timing on the relationship between fractionation and OS. Early concurrent chemotherapy consisted of RT and chemotherapy initiated within 30 days of each other. In our NSCLC study we performed subset analyses to determine the impact of dose escalation. Of the 7,143 patients included in our LS-SCLC study, 97.9% received standard RT and 2.1% HFRT. Among the 2,159 patients in our NSCLC study, 63.2% underwent CFRT, 23.5% LD-HFRT, and 13.3% HD-HFRT. There were no significant differences in OS between HFRT and standard RT in LS-SCLC, or between HFRT and CFRT in stage I NSCLC on MVA. Among patients with LS-SCLC, OS was shorter with HFRT in the early concurrent chemotherapy subset and longer with HFRT in the non-early concurrent chemotherapy subset, suggesting that chemotherapy timing may modify the effect of fractionation on OS in this setting. Among patients with stage I NSCLC, OS was significantly longer with HD-HFRT compared to CFRT, although OS was similar in comparing LD-HFRT and CFRT. Our results indicate that HFRT may be considered over standard RT in LS-SCLC (especially in patients unable to receive early concurrent chemotherapy) and over CFRT in stage I NSCLC (especially when dose escalation is safe and feasible).


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