Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years?

Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer

Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)

Prognostic factors for patients with limited-stage small-cell lung cancer without receiving prophylactic cranial irradiation

Objective:This retrospective study aims to explore the risk factors for brain metastasis and the prognostic factors for overall survival(OS)in patients with limited-stage small-cell lung cancer(LS-SCLC)who have no brain metastases according to magnetic resonance imaging(MRI)and have not received prophylactic cranial irradiation(PCI)after first-line chemoradiotherapy.Methods:A total of 107 patients who were treated in the Fourth Hospital of Hebei Medical University from January 2013 to December 2017 were enrolled in this study.The patients were treated with etoposide/platinum chemotherapy and thoracic radiotherapy(TRT)with involved-field irradiation.The median dose of the radiotherapy was 60 Gy(50-64 Gy).The primary study endpoints include BMFS(brain-metastasis-free survival)and OS(overall survival).The Kaplan-Meier method was applied to estimate survival,with a log-rank test used to ascertain statistical significance.The multivariate Cox proportional hazards model was used to determine the prognostic factors for survival.Results:The median follow-up of all patients was 18.8 months(range:7.9–65.1 months)and the median follow-up of surviving patients was 26.7 months(range:18.8–65.1 months).The median OS of the whole cohort was 20.1 months,and the 1-,2-and 3-year OS rates were 84.9%,44.9%,and 25.9%,respectively.The 1-,2-,and 3-year BMFS rates were 69.0%,49.9%,and 40.7%,respectively.50 patients(46.7%)developed brain metastases during the follow-up period,and the median time from the start to brain metastasis was 10.7 months(range:4.8–31.1 months).As shown by multivariate analysis,independent prognostic factors of OS included cycles of chemotherapy(P=0.019),the response to initial treatment(P=0.011),and the start time of TRT(P=0.044).The independent prognostic factors of BMFS included the clinical stage(P=0.008),the response to initial treatment(P=0.024),and the start time of TRT(P=0.028).Conclusions:For patients with LS-SCLC who have not received PCI,favorable factors for lower brain metastasis and higher survival include early clinical stage,CR to initial chemoradiotherapy,early TRT,and adequate cycles of chemotherapy.PCI is still recommended as the standard modality since the incidence of brain metastases was high(46.7%).