Prognostic Impact of ABO/Rh Blood Group-Systemic Inflammation Indices Interactions in Small-Cell Lung Cancer

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.