Abstract
ObjectiveThe purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT.MethodsA total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher’s exact tests. Kaplan–Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models.ResultsPatients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05).ConclusionCHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.
Highlights
Small cell lung cancer (SCLC) accounts for approximately 13–15% of primary lung cancers and is characterized by its highly aggressive nature, early dissemination and good response to treatment, with almost two-thirds of SCLC patients presenting in an extensive stage (ES) at the first clinical diagnosis [1, 2]
The aims of this study were as follows: first, to characterize whether thoracic radiation (TRT) added to CHT (CHT/TRT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC); second, to explore the appropriate TRT time and optimal radiation dose/fraction for survival; and third, to identify prognostic factors influencing the clinical outcome for ES-SCLC patients to distinguish who would benefit from CHT/TRT
Considering the current and previous reports, there is no doubt that TRT could improve survival in ES-SCLC patients
Summary
Small cell lung cancer (SCLC) accounts for approximately 13–15% of primary lung cancers and is characterized by its highly aggressive nature, early dissemination and good response to treatment, with almost two-thirds of SCLC patients presenting in an extensive stage (ES) at the first clinical diagnosis [1, 2]. Prior studies have demonstrated that TRT plays a vital role in terms of regional control and improved survival for ES-SCLC patients. Several retrospective analyses suggested that TRT in combination with CHT was associated with long-term survival [14,15,16,17,18] This treatment strategy was advocated for certain ES-SCLC patients both in the 2020 NCCN guidelines [19] and in the ASTRO 2020 guidelines [20]. In the absence of TRT, as a first-line treatment, IO with the incorporation of atezolizumab or durvalumab into the CHT scheme has prolonged survival, making the role of TRT even more unclear The aims of this study were as follows: first, to characterize whether TRT added to CHT (CHT/TRT) showed promising anti-tumour activity in ES-SCLC; second, to explore the appropriate TRT time and optimal radiation dose/fraction for survival; and third, to identify prognostic factors influencing the clinical outcome for ES-SCLC patients to distinguish who would benefit from CHT/TRT
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