2405 - Optimizing Chemoradiotherapy for Small Cell Lung Cancer in the Immunotherapy Era

Purpose/Objective(s): Based on recent trials, most patients with limited stage small cell lung carcinoma (LS-SCLC) will be treated with concurrent chemoradiotherapy followed by adjuvant immunotherapy. However, lymphopenia is a known complication of chemoRT and has been associated with worse survival outcomes. The purpose of this study is to identify the factors which contribute to lymphopenia in this patient population and explore the potential impact on patterns of failure.

Materials/Methods: This retrospective study analyzed LS-SCLC patients treated with chemoRT at a single institution from 2004 to 2024. Patients were included if they completed concurrent chemoRT and had comprehensive treatment records available. Patient and treatment characteristics were tested as predictors of acute grade 3-4 (G3-4) lymphopenia and ALC nadir using logistic and linear regression models. and competing risks analyses were utilized to quantify rates of in-field and out-of-field disease progression.

Results: A total of 92 patients who underwent chemoRT for LS-SCLC were screened, with 78 meeting inclusion criteria. The median age was 66, and most patients (78%) had stage III disease. BID treatment was delivered in 26 patients (33%), and 27 (34%) received prophylactic cranial irradiation (PCI). The median ALC nadir was 400 per µl, and 74% of patients developed grade 3-4 lymphopenia. Receipt of cisplatin (v. carboplatin) was associated with more severe lymphopenia (G3-4 lymphopenia rate 87% v. 59%, p=0.036). No other treatment-related factors, including radiotherapy fractionation and extent of irradiation of the heart, lungs, esophagus, and thoracic spine, were significantly associated with lymphopenia severity. Disease progression was confirmed in 45 patients, and the first site of progression was in-field for 16 (20%) patients and in the brain for 17 (21%). Other sites included out-of-field thoracic recurrence (5 patients), liver (2 patients), spine (1 patient), and other sites (1 patient). The three-year cumulative incidence rate (CIR) of out-of-field disease progression was 42%, and the three-year CIR for in-field progression was 21%, and there was a trend suggesting that G3-4 lymphopenia is a risk factor for out-of-field disease progression (Fine and Gray’s subhazard ratio 4.22, 95% CI 0.88-20.19, P=.071).

Conclusion: Patients with LS-SCLC who are treated with concurrent chemoRT frequently experience severe lymphopenia, which may be an important risk factor for distant disease progression in the era of adjuvant immunotherapy. Future studies in this patient population should explore strategies to mitigate treatment-related immunosuppression.