Comprehensive analysis of radiographic, clinical, and inflammatory markers demonstrating changes in lean muscle correlate with outcome in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) who undergo taxane-based chemotherapy (CT)
| Autor: | Anne M. Noonan, Chul Ahn, Gregory B. Lesinski, Matthew R. Farren, Veena Nagar, Michael V. Knopp, Tanios Bekaii-Saab, Daniel H. Ahn |
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| Rok vydání: | 2016 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Chemotherapy Pathology Taxane business.industry Proportional hazards model medicine.medical_treatment Skeletal muscle Metastatic Pancreatic Adenocarcinoma medicine.disease SMA Cachexia Clinical trial medicine.anatomical_structure Internal medicine medicine business |
| Zdroj: | Journal of Clinical Oncology. 34:349-349 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 349 Background: MPDAC is associated with a poor prognosis. The mechanisms of carcinogenesis are complex; involve multiple signaling pathways and inflammatory cytokines that may promote cachexia, a major cause of morbidity and mortality in mPDAC. The purpose of this study is to understand factors related to skeletal muscle changes, and its effect on outcomes in pts with mPDAC. Methods: Pt and clinical data were obtained from a recent prospective clinical trial in mPDAC where all pts received first-line taxane-based CT. We examined changes in modified Glasgow prognostic score, neutrophil lymphocyte ratio, a 32-cytokine panel, weight, and skeletal muscle area (SMA), determined by validated methodology with computed tomography, at baseline and cycle 3. We defined > 6cm2 in SMA, correlating to 1kg of skeletal muscle gain (SMG), as significant. Univariate and multivariate Cox regression models were used to determine the association between laboratory, radiographic and clinical findings with progression free survival (PFS) and overall survival (OS). Results: 66 evaluable pts were included. Independent of clinical response, an OS advantage was seen in pts who experienced significant SMG (p = 0.023) and in patients with nominal SMG (p = 0.012). A numerical benefit in PFS was observed with SMG. Decreases in IFN-a (p = 0.024), IFN-g (p = 0.001) and IL-6 (p = 0.042) were inversely associated with SMG. A comprehensive analysis incorporating all relevant laboratory, radiographic and clinical assessments demonstrated a 4.62-month OS advantage in pts with favorable characteristics vs. those with poor prognostic factors (11.47 versus 6.84 mos., p = 0.0029). Conclusions: SMG, or the reversal of cachexia confers an OS advantage in pts with mPDAC treated with taxane-based CT regardless of clinical response. A comprehensive assessment of muscle change is a precise measurement that can identify pts at greatest risk for muscle loss, which could predict for trmt response and pt outcomes. This merits further investigation as a tool and in trials directed at reversing the process of cachexia. |
| Databáze: | OpenAIRE |
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