Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.386
Peer-review started: October 26, 2023
First decision: December 2, 2023
Revised: December 14, 2023
Accepted: January 10, 2024
Article in press: January 10, 2024
Published online: February 15, 2024
Cancer-related inflammation manifests both at the site of the tumor and systemically, releasing acute phase proteins and circulating immune cells into the bloodstream. Against this inflammatory backdrop, the systemic inflammatory response index (SIRI) based on neutrophil, monocyte, and lymphocyte counts, has emerged as a prognostic factor in pancreatic cancer. Its utility extends to predicting overall survival (OS) in those undergoing chemotherapy, reflecting the status of both the immune response and systemic inflammation. One of the most conspicuous and clinically evident outcomes of the pro-inflammatory state is the anorexia-cachexia syndrome. While malnutrition and cachexia are acknowledged as adverse prognostic factors, the correlation between serum pro-inflammatory mediators and nutritional parameters, as well as the combined or individual contribution of each to prognosis, has yet to be clearly defined.
For patients with advanced pancreatic cancer, the systemic inflammatory response triggered by the disease often precipitates malnutrition. This is evident in cancer cachexia, a multifactorial hypermetabolic state characterized by involuntary weight loss, skeletal muscle depletion, and potentially, reduction in body fat. Unfortunately, traditional nutritional interventions might not effectively counteract this condition.
The primary objective of this pilot study, conducted as part of the PANTHEIA-Spanish Society of Medical Oncology (SEOM) initiative, is to analyze the utility of SIRI as a prognostic factor for response in patients with metastatic pancreatic cancer and to investigate its association with weight loss.
This study included patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained 15 d before initiation chemotherapy. Originating from the PANTHEIA-SEOM initiative, a multicentric, observational, study promoted by the SEOM Real World-Evidence work group, our pilot research seeks to bridge this knowledge gap. Specifically, we focused on the interplay between weight loss and the inflammatory state as demarcated by SIRI.
We examined the survival outcomes of patients based on weight loss prior to diagnosis. The median OS for patients who experienced a weight loss > 5% in the three months before diagnosis was notably shorter than for those who did not, 6 mo compared to 19 mo, respectively, P = 0.003. However, within the low SIRI subgroup (< 2.3 × 10³/L), patients with low albumin levels (< 3.5 g/dL) tended to have worse OS (9 mo) compared to those with higher albumin levels (16 mo, P = 0.869). In patients with high SIRI values, albumin levels did not significantly affect survival outcomes. In the exploratory analysis of survival outcomes based on weight loss and SIRI values, the most striking difference was among patients with low SIRI levels (< 2.3 × 103/L): Those without weight loss of > 5% had a median OS of 20 mo compared to 11 mo for those who did have a weight loss of > 5%. In this pilot study, an elevated SIRI was suggested to be predictive of lower OS, progression free survival, and increased weight loss.
Our findings indicate a significant correlation between elevated SIRI levels and decreased survival in patients with metastatic pancreatic cancer, with a notable association with weight loss. Furthermore, SIRI emerges as an independent prognostic factor of survival. By viewing SIRI as an emblem of systemic inflammation, we shed light on its potential link with the nutritional trajectories of these patients.
This revelation is paramount, as discerning the intricate web of systemic inflammation, weight loss and the cachexia-anorexia syndrome could pave the way for early interventions, potentially enhancing patient prognosis.