The Dose/Fractionation Debate in Limited-Stage Small Cell Lung Cancer.

Simple Summary: The selection of radiation dose/fractionation schemes for limited-stage small cell lung cancer (LS-SCLC) is highly controversial. It mainly involves the impact of total biologically effective dose, overall treatment time, and fractionation dose on survival and toxicity. This article comprehensively analyzes current relevant research and discusses the advantages and disadvantages of conventional-dose/fractionation radiotherapy (ConvTRT), hyperfractionated radiotherapy (HyperTRT), hypofractionated radiotherapy (HypoTRT), and stereotactic body radiotherapy (SBRT), in order to find the most suitable dose fractionation scheme and provide reference for clinical practice. Regardless of the radiotherapy modality, controlling the radiotherapy time to around 3 weeks is beneficial for improving survival and local control rates while reducing toxicity reactions. ConvTRT with a high total prescription dose is not recommended, because a prolonged radiotherapy time may reduce the tumor control probability of some rapidly proliferating tumor cells. In balancing acute reactions, late reactions, and treatment outcomes (local control or overall survival), the advantages of HyperTRT over HypoTRT still exist. For the radical radiotherapy regimen recommended by current guidelines (45 Gy/30 fractions), we suggest moderately increasing the fractionation dose and total dose, which may further improve prognosis. To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate (p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC. [ABSTRACT FROM AUTHOR]