Randomized phase II trial comparing the efficacy of standard-dose with high-dose twice-daily thoracic radiotherapy (TRT) in limited disease small-cell lung cancer (LD SCLC).

Abstract

9007 Background: Concurrent chemoradiotherapy is the standard treatment of LD SCLC. Some patients are cured, but most relapse and better treatment is needed. 45 Gy in 30 fractions BID is the most recommended TRT-schedule. Studies suggest that a higher TRT-dose might prolong survival, but hitherto, this has not been confirmed in randomized trials. We aimed to investigate whether high-dose BID TRT of 60 Gy in 40 fractions was feasible, tolerated, and improved survival. Methods: Patients > 18 years, performance status (PS) 0-2 and confirmed LD SCLC were to receive 4 courses of platinum/etoposide and were randomized to BID TRT of 60 or 45 Gy. Responders were offered prophylactic cranial irradiation of 25-30 Gy. Primary endpoint was 2-year survival; secondary endpoints were toxicity, progression free survival (PFS), and overall survival (OS). To demonstrate a 25% improvement of 2-year survival from 53% to 66% with a one-sided α = .10 and β = .80, 75 patients were required on each arm. Results: Between 2014-2018, 176 patients were enrolled at 22 Scandinavian hospitals. 160 completed TRT per protocol and were eligible for the present analyses (60 Gy: n = 84, 45 Gy: n = 76). Median age was 65, 58% women, 90% PS 0-1. There were no significant differences in grade 3–4 esophagitis (60 Gy: 19%, 45 Gy: 18%, p = .92) or grade 3–4 pneumonitis (60 Gy: 4%, 45 Gy: 0%, p = .10). There was a trend towards more neutropenic infections on the 45 Gy arm (60 Gy: 21%, 45 Gy: 36%, p = .05). There were no significant differences in other grade 3-4 toxicity. Three patients died during the study treatment period (60 Gy: one neutropenic infection and one aortic dissection; 45 Gy: one thrombocytopenic bleeding). There were no statistically significant differences in response rates (60 Gy: 88% [95% CI 81-95], 45 Gy: 85% [95% CI 76-93], p = .52) or median PFS (60 Gy: 20 months [95% CI 11-29], 45 Gy: 14 months [95% CI 10-19], p = .31). Significantly more patients on the 60 Gy arm were alive after 2 years (60 Gy: 73% [95% CI 63-83], 45 Gy: 46% [95% CI 36-60], p = .001), and they had a significantly longer median overall survival (60 Gy: 42 months [95% CI 32-51], 45 Gy: 23 months [95% CI 17-28], HR .63 [95% CI .41-.96], p = .031). Conclusions: LD SCLC patients who received BID TRT of 60 Gy had a statistically significant and numerically substantial benefit in terms of 2-year survival (primary endpoint) and median overall survival compared with those who received BID TRT of 45 Gy. The higher TRT dose did not cause more toxicity than the standard dose. Clinical trial information: NCT02041845.

Thoracic radiotherapy in small cell lung cancer—a narrative review

“…A recent phase II study comparing 45 to 60 Gy BD was reported at ASCO and ESMO 2020 in abstract form only. It showed an improvement in 2-year survival but it should be noted that this study is unpublished and included 170 patients (22). These results cannot therefore be considered practice changing and will require confirmation in a phase III study.…”

Simultaneous integrated dose reduction intensity-modulated radiotherapy effectively reduces cardiac toxicity in limited-stage small cell lung cancer

“…In addition, when the ENR was applied, only 11.3% (34/300) of patients had locoregional in-field failure. A randomized trial reported by the ASCO in 2020 compared the efficacy of a radiation dose of 45 Gy in 30 f BID with 60 Gy in 40 f BID TRT in patients with LS-SCLC and revealed that patients who received a dose of 60 Gy BID had a statistically significant benefit in 2-year survival and MST compared to patients who received a dose of 45 Gy BID 27 . Although the radiation modalities used in this study may be the most recommended TRT-schedule for LS-SCLC at present, only the 2-year survival of patients was evaluated and long-term survival remains to be assessed.…”

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

“…Recently, several phase III trials have reported better survival outcomes in patients with ES-SCLC when combining carboplatin-etoposide with atezolizumab[ 48 ] or durvalumab[ 49 , 50 ]. The results of two RCTs comparing dose escalation with the normofractionated scheme vs the “Turrisi” scheme are pending: CALGB 30610 (normofractionation to 70 Gy) and a Norwegian study involving high-dose (60 Gy) AHF-RT in the experimental arm[ 51 ].…”