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Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma.

ABSTRACT: Pancreatic cancer is characterized by a high rate of metastatic spread and overall poor prognosis. Yet 30% of patients have progressive local disease at the time of death, and local progression can cause significant morbidity. Approximately 30-40% of patients present with locally advanced pancreatic cancer (LAPC) that is not surgically resectable, and the optimal treatment for these patients continues to evolve. The role of radiation in the management of LAPC is an area of controversy, and the recent LAP07 randomized trial reported no survival benefit of radiation following gemcitabine plus or minus erlotinib. However, the efficacy of modern systemic regimens has improved since the design of the LAP07 study, and radiation therapy may be of greater benefit in the context of more effective systemic therapy. Advances in radiation delivery including the increasing use of stereotactic body radiation therapy (SBRT) have the potential to improve outcomes through dose escalation and better treatment tolerability. In addition, the combination of radiation therapy and immune therapy is an area of promising research. These advances suggest that radiation therapy will continue to play an integral role in the management of LAPC.

SUBMITTER: Blakaj A

PROVIDER: S-EPMC6286948 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma.

Blakaj Adriana A Stein Stacey M SM Khan Sajid A SA Johung Kimberly L KL

Journal of gastrointestinal oncology 20181201 6

Pancreatic cancer is characterized by a high rate of metastatic spread and overall poor prognosis. Yet 30% of patients have progressive local disease at the time of death, and local progression can cause significant morbidity. Approximately 30-40% of patients present with locally advanced pancreatic cancer (LAPC) that is not surgically resectable, and the optimal treatment for these patients continues to evolve. The role of radiation in the management of LAPC is an area of controversy, and the r ...[more]

PMID: 30603121

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Project description:PurposeStereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.Patients and methodsWe retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.ResultsA total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.ConclusionsLAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.

Project description:IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3-28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4-30.3) and 16.7 months (95% CI: 13.0-20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042-3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.

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Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma.

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Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma.

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