1. Prolonged chemotherapeutic down-staging before resection was associated with improved survival in patients with previously inoperable pancreatic cancers.
2. SMAD4 protein loss correlated significantly with overall survival.
Evidence Rating Level: 2 (Good)
Study Rundown: Pancreatic cancer is one of the most deadly malignancies, and pancreatic ductal adenocarcinoma in particular has a 5.8% 5-year overall survival (OS. Patients with locally invasive disease may be treated with downstaging chemotherapy to reduce vascular involvement, but this approach is not yet standardized and produces variable results. In this study, the authors investigated the effect of a median 7.1 months (range 5.4-9.6 months) of chemotherapy before resection, and found 75.5% of patients to be lymph-node negative, with a median OS of 40.1 months (range 22.7-65.9 months). Additionally, multivariate modeling of prognostic biomarkers showed SMAD4 protein loss to affect OS. This study provides good evidence for modifying treatment practices for advanced pancreatic cancer, with plenty of pathologic and outcome data. A more detailed analysis of the effect of duration of chemotherapy on outcomes would be prudent, as the range spanned more than four months and may include a threshold.
Relevant Reading: Treatment options for advanced pancreatic cancer: a review
In-Depth [retrospective cohort study]: All patients from UCLA diagnosed from 1992-2011 with initially unresectable stage III pancreatic ductal adenocarcinoma who underwent resection after down-staging were included in the analysis (n=49). All patients were initially unresectable owing to tumor vascular involvement. Most received a multidrug regimen based on gemcitabine or 5-FU, and most also received a pylorus-sparing Whipple. Resolution of vascular involvement occurred in 15 patients. Most patients (75.5%) had lymph node-negative disease at time of resection, which correlated with longer survival. Patients with negative lymph nodes after resection may have experienced a longer duration of chemotherapy (this finding was not statistically significant). Recurrence occurred in 49% of cases, only 12.5% of which was local. SMAD4 and stromal miR-21 correlated with OS on univariate Cox analysis, but only SMAD-4 was significant in the multivariate model (HR 9.3, 95%CI 2.0-42.5, p=0.004).
By Mariya Samoylova and Allen Ho
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