Severe radiation-induced lymphopenia and its impact on overall survival in solid tumors: A scoping review of systematic reviews

Radiation therapy is a cornerstone of treatment for solid tumors, yet it often induces lymphopenia, a condition linked to poorer clinical outcomes. This scoping review synthesizes evidence from systematic reviews to evaluate the prognostic impact of severe radiation-induced lymphopenia (RIL) on overall survival (OS) in patients with solid tumors. A systematic literature search was conducted across PubMed, Cochrane Central, and EMBASE using the following keywords: "radiation," "lymphopenia," "solid tumors," "survival AND mortality," and "systematic review AND meta-analysis," up to November 30, 2023. Reviews reporting the prognostic relationship between RIL and survival were included, and pooled adjusted hazard ratios (aHRs) were calculated using a random-effects model. Subgroup analyses examined the impact of grade 3 or higher RIL across different tumor types. Of 21 identified reviews, 10 were included, covering 93 studies and 11,565 patients. The adjusted incidence rate of severe lymphopenia averaged 26.7% (range: 18.6-88.0%). The pooled aHR for OS was 1.72 (95% CI: 1.33-1.87) for grade ≥3 RIL versus grade 0-2 RIL, and 1.59 (95% CI: 1.31-1.92) for grade 4 RIL versus grade 0-3 RIL. Significant prognostic effects were observed in esophageal, head and neck, pancreatic, cervical, central nervous system, and lung cancers. Genitourinary tumors showed associations with medium-high radiation doses to pelvic and iliac bone marrow. Severe RIL consistently predicts poorer OS, emphasizing the need for prospective studies to address RIL prevention and management, especially in the era of immunotherapy.