Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer

Abstract

BackgroundPrevious data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy.MethodsMedical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ 2 test.ResultsA total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815).ConclusionThis retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.

Is There a Role for Hypofractionated Thoracic Radiation Therapy in Limited-Stage Small Cell Lung Cancer? A Propensity Score Matched Analysis

“…[33][34][35][36] Zhang et al and Videtic et al concluded that HFRT and CFRT regimens yield similar OS, local control, treatment failure patterns, and toxicity outcomes, corroborating our findings. 33,34 Bettington et al suggested that 40 Gy in 15 fractions and 45 Gy in 30 fractions, given twice daily, provided equivalent relapse-free survival rates. 36 Turgeon et al only described local control and OS rates in 68 patients treated with 40 Gy in 16 fractions, with no comparison or control group.…”

Accelerated Hypofractionated Radiotherapy and Concurrent Etoposide/Cisplatin in Patients with Limited-Disease SCLC (LD-SCLC)

“…In the current study the median PFS was 16.7 months (95% CI, 6.7 -19.0 months), and 1-, and 2-years PFS rates were 60%, and 41.4%, respectively, when compared to the study by Zhang et al [30], where the median PFS was 18.2 months (95% CI: 15.8 -20.6 months), and the 1-year and 2-year PFS rates were 64.8% and 32.4%, respectively. The median OS in our study was 26.4 months (95% CI, 10.4 -28.1 months), and 1-, and 2-years OS rates were 78% and 58.3%, compared to the results of the study by Zhang et al [30], where the median OS was 27.2 months (95% CI: 25.2 -29.2 months), and the 1-and 2-year survival rates were 87.0% and 62.2%, respectively. As a natural behavior of SCLC, distant metastasis was reported to be the most common pattern of failure which occurred in 50% of the patients in our study, while 17% patients developed locoregional recurrence.…”

“…In the current study ORR was reported to be 90%, while in a similar trial done by Zhang et al in the HYPO-RT arm, ORR was 97% [30]. In the current study the median PFS was 16.7 months (95% CI, 6.7 -19.0 months), and 1-, and 2-years PFS rates were 60%, and 41.4%, respectively, when compared to the study by Zhang et al [30], where the median PFS was 18.2 months (95% CI: 15.8 -20.6 months), and the 1-year and 2-year PFS rates were 64.8% and 32.4%, respectively. The median OS in our study was 26.4 months (95% CI, 10.4 -28.1 months), and 1-, and 2-years OS rates were 78% and 58.3%, compared to the results of the study by Zhang et al [30], where the median OS was 27.2 months (95% CI: 25.2 -29.2 months), and the 1-and 2-year survival rates were 87.0% and 62.2%, respectively.…”

“…In our study we recruited 30 patients with LD-SCLC, 93% of the patients were men [16]. In the current study ORR was reported to be 90%, while in a similar trial done by Zhang et al in the HYPO-RT arm, ORR was 97% [30]. In the current study the median PFS was 16.7 months (95% CI, 6.7 -19.0 months), and 1-, and 2-years PFS rates were 60%, and 41.4%, respectively, when compared to the study by Zhang et al [30], where the median PFS was 18.2 months (95% CI: 15.8 -20.6 months), and the 1-year and 2-year PFS rates were 64.8% and 32.4%, respectively.…”

A framework for the development of effective anti-metastatic agents

“…Subgroups of patients with an especially high risk of early distant metastases are clearly identifiable. Examples include those with limited-stage small-cell lung carcinoma 129 , locally advanced pancreatic ductal adenocarcinoma 130 or colorectal cancer and resectable liver metastases 131 . These disease settings are attractive both commercially and clinically, although reliance on such populations for early go versus no-go decisions holds the risk that effective anti-metastatic drugs will be prematurely discarded.…”