Simultaneous Integrated Dose Reduction Radiation Therapy Versus Conventional Fractionated Radiation Therapy With Chemotherapy for Limited-Stage Small Cell Lung Cancer in the Modern Treatment Era: A Phase 3, Randomized Clinical Trial (SDR-RT trial).

PURPOSE: Simultaneous integrated dose reduction (SDR) radiation therapy (SDR-RT) with a definitive dose to the gross tumor volume (GTV) and a relatively lower dose to the clinical target volume (CTV) might be beneficial in improving normal tissue sparing with low toxicity. We aimed to compare the efficacies of SDR-RT and conventional fractionated radiation therapy (CF-RT) for limited-stage small cell lung cancer (LS-SCLC).

METHODS AND MATERIALS: Eligible patients with LS-SCLC were 1:1 randomized to receive CF-RT (60 Gy in 30 once-daily fractions over 6 weeks for both CTV and GTV) or SDR-RT (50 Gy for CTV and 60 Gy for GTV in 28 once-daily fractions over 5.5 weeks) along with 4 to 6 cycles of chemotherapy. The primary endpoint was progression-free survival (PFS) rate in the intention-to-treat population, whereas the secondary endpoints were overall survival rate and adverse event incidence.

RESULTS

Between February 2017 and March 2023, 336 patients randomly received either SDR-RT (n = 165) or CF-RT (n = 171). Over a median follow-up of 56 months, the 2- and 5-year PFS rates in the intention-to-treat analysis were, respectively, 42.0% and 31.9% with SDR-RT, and 40.7% and 30.5% with CF-RT (P = .015 for noninferiority). The between-group differences in overall survival, locoregional PFS, and locoregional recurrence rates were nonsignificant. Compared with CF-RT, SDR-RT was associated with lower median values of V20 (21.0% vs 22.8%) and Dmean (12.1 vs 13.4 Gy) of the bilateral lungs (both P < .001). Acute grade ≥3 toxicities and radiation pneumonitis incidence were lower with SDR-RT than that with CF-RT (54.5% vs 66.9%, P = .020; 2.4% vs 7.7%, P = .027).

CONCLUSIONS

Compared with CF-RT, SDR-RT led to similar survival and less acute adverse events. SDR-RT may be considered as a more protective approach for LS-SCLC treatment.