Objective:To assess the clinical outcomes and toxicities of once daily (QD) simultaneous dose reduction intensity-modulated radiotherapy (SDR-IMRT-QD; SDR-QD) versus conventional QD IMRT (C-QD) and twice daily (BID) IMRT in patients with limited-stage small cell lung cancer (LS-SCLC).Methods:After propensity score matching (PSM), a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD, C-QD, or BID was performed from January 1, 2014 to December 31, 2019. The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD. The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort. The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort. Toxicities, short-term effects, and survival outcomes were recorded. A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time (MST) in the 3 cohorts were 32.7 months (SDR-QD), 26.3 months (C-QD), and 33.6 months (BID); the differences between groups were statistically significant. Lower toxicities and doses to organs-at-risk (OARs) occurred in the SDR-QD and BID cohorts. Further, the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival (r= −0.35,P= 0.007). A Vheart40 value of 16.5% was recommended as a cut-off point, which yielded 54.7% sensitivity and 85.7% specificity for predicting negative survival outcomes. The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy, but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID, but fewer toxicities and better survival than C-QD. In addition, cardiac dose exposure was negatively associated with survival. Thus, 16.5% of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point, and a Vheart40 > 16.5% predicts poor survival.