PubMed · 3285792
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B Beutler, A Cerami. 1988. Cachectin, cachexia, and shock.. https://doi.org/10.1146/annurev.me.39.020188.000451
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PURPOSE: To develop and internally validate the PANTHEIA-SIRI prognostic model, which integrates log-transformed systemic inflammation response index (SIRI) with clinical predictors, to estimate overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line chemotherapy. METHODS: We used data from the multicenter PANTHEIA-SEOM registry. OS was defined from chemotherapy start. The model was fitted as a Weibull accelerated failure time model in the survival-analysis population with multiple imputation. Predictors were log-transformed baseline SIRI, modeled with restricted cubic splines, ECOG, tumor burden, chemotherapy regimen, and anorexia-cachexia syndrome. Internal validation used a separate, non-overlapping cohort from the same registry; the centers contributing to each cohort are listed in a supplementary annex. TRIPOD was followed. Discrimination was assessed with Harrell´s C-index and calibration with IPCW Brier scores and IPA. RESULTS: The derivation cohort comprised 672 patients with SIRI data (593 analyzed for survival) across 22 Spanish hospitals (2015-2025); 80.1% had died after a median OS of 9.9 months. The imputation-pooled derivation C-index was 0.654 (95% CI, 0.627-0.681); optimism-corrected, 0.629. Internal validation used 62 separate patients from the same registry; 96.8% had died after a median OS of 9.2 months. The validation C-index was 0.603 (95% CI, 0.518-0.687). Calibration was adequate at 6 and 12 months. CONCLUSIONS: The PANTHEIA-SIRI model provides individualized OS estimates in mPDAC with routine clinical predictors. Its open-access calculator ( https://pantheia-siri.shinyapps.io/calc/ ) may support prognostic communication, treatment-intensity selection, and supportive-care planning. Routine clinical implementation will require further validation in larger, fully independent cohorts.
Cancer cachexia is a syndrome with weight loss, anorexia, and loss of host body cell mass. Tumor cachexia may be an early symptom of a neoplasm. Low food intake is the main reason for weight loss. Surgery, chemotherapy and radiation remain primary therapeutic modalities to overcome cancer cachexia. Artificial nutrition is able to avoid progressive weight loss; nutrition alone may not preserve fat-free body cell mass. Parenteral nutrition reduces perioperative morbidity and mortality. Nutritional support failed to show a benefit in patients with malignancies which are treated with therapeutic radiation or chemotherapy. For patients with unresectable neoplasms of the upper GI-tract conventional palliative regimens (bougienage, laser, etc.) do not support a satisfactory nutritional state. Ambulatory enteral tube feeding via percutaneous endoscopic gastrotomy (PEG) as an adjunct to therapy is useful and safe in providing adequate fluid and substrates.
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