Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era

Abstract

Introduction: The role of consolidative thoracic and prophylactic brain radiation for extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether RT has a benefit to overall survival (OS) in patients receiving any systemic therapy and whether this benefit is the same if Chemotherapy (CT) or chemo-immunotherapy (CT-IO) is used.

Material/methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, be treated 2-6 months from diagnosis, and if treated to the brain received 25 Gy in 10 fractions only. Multi-variable analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS.

Results: The total number of patients receiving RT/STX or STX alone as well as their median follow-up (months) were (890, 17.0 mn) and (6898, 14.0mn). The median time to the start of STX and RT were 22.9 days and 152 days, respectively. MVA noted that RT had a greater effect on OS (Thorax, Brain, Both Brain/Thorax - HRs = 0.80, 0.77, 0.70) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.06). Selection for radiation depended significantly upon factors affecting OS (HR) including lack of liver metastases, females, age and Charlson co-morbidity index, but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity-score matched OS curves noted the same significant effects of RT on OS in those receiving CT +/- IO, CT-IO, and CT alone with HRs of 0.68/0.68/0.68 for thoracic RT, 0.72/0.72/0.70 for brain RT, and 0.60/0.60/0.60 for brain/thoracic RT, respectively.

Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy.

Keywords: Consolidative thoracic radiation; Extensive-stage small cell lung cancer; Immunotherapy; Prophylactic cranial radiation; Survival benefit.