Using the Systemic Immune-Inflammation Index (SII) as a Mid-Treatment Marker for Survival among Patients with Stage-III Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3-4) is a significant predictor of survival, and if the effect of PEM vs. ETO differs by quartile (Q) level of SII. Hazard-ratios (HR) for survival were estimated using a proportional hazards model, accounting for the underlying correlated structure of the data. A total of 548 patients were included in our analysis. The median age at baseline was 59 years. Patients were followed for a median of 24 months. Adjusting for age, body mass index, sex, race, and chemotherapy regimen, SII was a significant mid-treatment predictor of both overall (adjusted HR (aHR) = 1.6, p < 0.0001; OS) and progression-free (aHR = 1.3, p = 0.0072; PFS) survival. Among patients with mid-RT SII values above the median (6.8), those receiving PEM (vs. ETO) had superior OS (p = 0.0002) and PFS (p = 0.0002). Our secondary analysis suggests that SII is an informative mid-treatment marker of OS and PFS in locally advanced non-squamous NSCLC.