Background/Objectives: ABO/Rh blood groups and systemic inflammation are each linked to cancer biology and prognosis, yet their combined and interactive prognostic value has not been clarified in small-cell lung cancer (SCLC). We investigated the distribution of ABO/Rh blood groups in SCLC, their association with baseline complete blood count (CBC)–derived inflammatory indices, and the prognostic significance of blood group–inflammation interactions for treatment response and survival outcomes. Methods: This retrospective study included 158 patients with SCLC with available ABO/Rh typing and pretreatment CBC data. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), and systemic inflammation response index (SIRI) were calculated using standard formulas. Treatment response was assessed according to RECIST v1.1 and categorized as response (CR/PR) versus non-response (SD/PD). Progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression models incorporating interaction terms. Results: Patients with blood group O exhibited consistently lower baseline inflammatory indices compared with non-O blood groups. Non-O blood group status and higher SIRI independently predicted chemoradiotherapy non-response. Among the evaluated indices, SIRI demonstrated superior diagnostic performance compared with SII, NLR, and PLR. Similarly, non-O blood group status and higher SIRI were independently associated with increased risks of progression and mortality. In joint analyses, compared with blood group O and low SIRI (reference), the highest risk of progression was observed in patients with blood group AB × high SIRI (HR 14.67), followed by blood groups A × high SIRI (HR 10.38) and B × high SIRI (HR 7.95). A similar pattern was observed for mortality, with the highest risk in patients with blood group AB × high SIRI (HR 22.76), followed by blood groups A × high SIRI (HR 13.93) and B × high SIRI (HR 12.41). Conclusions: ABO blood group is associated with distinct inflammatory profiles in SCLC. Elevated SIRI independently predicts treatment non-response and adverse survival, and its prognostic effect varies by blood group, underscoring the role of host biology in modulating systemic inflammation.
Yıldız et al. (Wed,) studied this question.