Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer

Abstract

Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Current and future biomarkers for pancreatic adenocarcinoma

“…108,109 For pancreatic cancer, an unfavorable PS is an independent negative prognostic marker. 110,111 Especially with regard to an optimal treatment choice, ECOG PS should be considered as a valuable marker because PDAC patients with poor PS usually do not benefit from combination or intensified chemotherapy regimens such as FOLFIRINOX. 112 Furthermore, patient's age significantly influences survival in pancreatic cancer.…”

<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

“…27 In PDAC, more than 80% of the patients present with metastasis upon diagnosis. [27][28][29] Therefore, many efforts have been made in aims to suppress the metastatic property of PDAC. Metastasis is a complicated multi-step process involves the ability of cancer cell to detach by losing cellto-cell junction and cellular polarity, break away from the extracellular matrix, attain increased motility and increased invasive phenotype.…”

Metastasierung von Pankreastumoren

“…Besonders entscheidend für die Prognose des Pankreaskarzinoms ist die Metastasierung. Diese ist v. a. deshalb von außer-ordentlicher Bedeutung, weil ungefähr die Hälfte aller Pankreaskarzinome bei Diagnose bereits metastasiert sind [22].…”

“…Bei ungefähr 50 % der Patienten liegen daher zum Zeitpunkt der Diagnosestellung bereits Fernmetastasen vor, bei weiteren ca. 30-40 % eine lokal fortgeschrittene Erkrankung, sodass nur 10-20 % der Patienten überhaupt für eine kurative Resektion in Frage kommen [22]. Darüber hinaus versterben 80-90 % der mit kurativer Intention resezierten Patienten schlussendlich im Verlauf der Erkrankung.…”