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. Author manuscript; available in PMC: 2021 Mar 1.
Published in final edited form as: Ann Surg Oncol. 2019 Dec 10;27(3):907–908. doi: 10.1245/s10434-019-08136-7

ASO Author Reflections: Systemic Immune-Inflammation Index (SII) as a Biomarker of Response to Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma

Pranav Murthy 1, Brian A Boone 2
PMCID: PMC7490754  NIHMSID: NIHMS1621145  PMID: 31823171

PAST

Despite the increasing utilization of neoadjuvant therapy for the treatment of pancreatic adenocarcinoma (PDAC), biomarkers of response are limited. Accurate prediction of treatment response is extremely useful in clinical decision making, particularly when considering the duration and selection of individual agents for preoperative treatment. Importantly, cross-sectional imaging fails to predict response accurately or resectability following preoperative treatment.1,2 CA 19-9 is a validated prognostic marker in PDAC patients, with a decrease in CA 19-9 following treatment associated with a higher likelihood of margin negative resection and improved overall survival.3 However, CA 19-9 is not elevated in a significant number of patients with PDAC, resulting in the need for additional biomarkers of treatment response. The systemic immune-inflammation index (SII), calculated using absolute platelet, neutrophil, and lymphocyte counts, has recently emerged as a predictor of survival in patients with pancreatic ductal adenocarcinoma (PDAC) when assessed at diagnosis.4,5 In the current study, we sought to determine whether SII reflected treatment response and outcomes following neoadjuvant treatment for PDAC.

PRESENT

In this retrospective analysis of more than 400 patients, elevated post-treatment SII as a continuous variable and post-treatment SII of greater than 900 were independently associated with worse overall survival.6 In contrast to previous studies, baseline SII in patients who received preoperative treatment was not associated with any clinical outcome, suggesting that neoadjuvant treatment altered the biology and prognostic implications of these immune and inflammatory subsets.4,5 These findings suggest that outcome is determined primarily by how a patient’s SII responds to preoperative treatment, more than the SII at presentation. Administration of 5-FU-based regimens and a greater number of treatment cycles were associated with a greater decrease in SII following treatment. Importantly, change in SII was closely associated with change in CA 19-9 following neoadjuvant treatment, which has important clinical implications. The means by which proinflammatory neutrophils and platelets respond to tumor death and damage, and the facilitatory role of anticancer immune lymphocytes suggests the presence of deeper biologic mechanisms, available for further investigation.7

FUTURE

These findings suggest that the SII is a useful biomarker of response in patients with PDAC receiving treatment with neoadjuvant therapy. Further investigation is required to validate this single-institution analysis before implementation in clinical decision making. Importantly, change in SII was closely associated with change in CA 19-9. Because up to 20% of patients do not express CA 19-9, there may be utility in using SII as a biomarker of response in these patients. Additional study of the prognostic value of SII in this specific patient population is warranted.

Footnotes

DISCLOSURE The authors report no conflicts of interest.

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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