Margin status and neoadjuvant chemoradiation in patients with borderline resectable pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 304-304
Author(s):  
Pavlos Papavasiliou ◽  
Jonathan R Piposar ◽  
Rodrigo Arrangoiz ◽  
Kathryn T Chen ◽  
Fang Zhu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Free Survival ◽  
Positive Margin ◽  
Neoadjuvant Chemoradiation ◽  
Margin Status ◽  
Negative Margin ◽  
Resectable Pancreatic Cancer ◽  
Consensus Definition ◽  
Borderline Resectable ◽  
Positive Margins

304 Background: The objective of this study was to examine the effect of margin status and neoadjuvant therapy in determining outcomes for borderline resectable (BLR) pancreatic cancer and how neoadjuvant chemoradiation impacts margin of resection. Methods: A retrospective chart review was conducted to identify patients who underwent resection for BLR pancreatic cancer based on the AHPBA/SSO/SSAT consensus definition. Outcomes including overall survival (OS) and disease free survival (DFS) were determined based on margin status, location of positive margin (artery, vein, or pancreas), and receipt of neoadjuvant chemoradiation. Results: One hundred and three patients who met the definition of BLR pancreatic cancer and underwent resection between April 1993 and July 2010 were reviewed. Mean age at diagnosis was 65 with a median follow up time of 19.7 months. Neoadjuvant chemoradiation was administered in 49.5% of patients. Twenty-five percent of patients underwent portal and/or superior mesenteric vein resection, and 7% hepatic artery resection. Microscopic positive margin rate was 54%. Median OS was 17.2 months for patients with positive margins versus 24.9 months for patients with negative margins (p=0.003). Median DFS was 13.1 months for patients with positive margins versus 18.6 months for patients with negative margins (p=0.001). There was no difference in OS or DFS for patients with positive margins based on location or number of positive margins. Of the patients who received neoadjuvant chemoradiation, 61.7% had a negative margin of resection versus a 38.3% negative margin of resection rate for patients who did not receive neoadjuvant chemoradiation (p=0.02). Among patients with a positive margin, there was no difference in OS or DFS with or without neoadjuvant chemoradiation. Conclusions: A positive margin of resection, irrespective of location or number, is associated with worse outcome in patients with BLR pancreatic cancer. The use of neoadjuvant chemoradiation is associated with higher rates of margin free resection.

Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 280-280
Author(s):  
Jose Mario Pimiento ◽  
Tai Hutchinson ◽  
Jill M. Weber ◽  
Manish R. Patel ◽  
Pamela Joy Hodul ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Multimodality Therapy ◽  
Cancer Center ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

280 Background: Multimodality therapy has been advocated for borderline resectable pancreatic cancer (BRCP); however, specific regimens vary widely by institution. Outcomes of these interventions need to be examined to inform future investigation of the optimal therapy for these patients. This study represents the experience of multimodality therapy for BRPC at an NCI designated cancer center. Methods: We identified all patients (pts) with operable pancreatic ductal adenocarcinoma (PDA) from 2006 to 2011. Patients were divided into two groups: resectable group and BRPC group as per the NCCN and AHPBA consensus guidelines. Primary outcomes were resection rate, microscopic negative margin (R0) resection rate, overall survival (OS), and disease free survival (DFS). Fisher's exact and chi-square were used for group comparison while Kaplan-Meier estimates was used for survival analysis. Results: 160pts were identified with operable PDA. 100 (63%) pts had resectable tumors, and 60 (37%) pts had borderline resectable tumors. Neoadjuvant therapy (NT) was administered to 0% in the group with resectable tumors, and 100% in the group with borderline resectable tumors. The resection rate was 100% in pts with resectable tumors and 58% in pts with borderline resectable tumors. R0 resection rates were 80% in the resectable tumors and 97% in the borderline resectable tumors following NT. Perioperative mortality was <1% (1/125) for resectable tumors and 0% in borderline resectable tumors. Median OS was 22.6 months (m) for pts that had resectable tumors and 13.9m for all pts with borderline resectable tumors (p=0.017); however, the median OS for resected pts with borderline resectable tumors was 21.5m (p=0.6). Improved DFS was seen in patients with resectable tumors when compared with resected borderline resectable tumors (15 vs. 9.5m; p=0.04). Conclusions: Multimodality therapy leads to high rates of R0 resections in borderline resectable pancreatic cancer; however 42% of patients progressed during NT. The overall survival for patients with resected borderline resectable pancreatic cancer following NT is similar to patients who undergo resection for resectable pancreatic cancer.

Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4125-4125 ◽  
Author(s):  
Matthew H. G. Katz ◽  
Gauri R. Varadhachary ◽  
Todd W. Bauer ◽  
Nicolas Acquavella ◽  
Nipun B. Merchant ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Treatment ◽  
Safety Data ◽  
Neoadjuvant Chemoradiation ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Resectable Disease ◽  
Post Surgery ◽  
Grade 3 ◽  
To Receive

4125 Background: Pancreatic cancer (PC) is a challenging target for immunotherapy.Tumor-infiltrating lymphocytes (TILs) do not reach the PC cells in significant numbers due to the presence of stroma and a suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of TILs in the PC microenvironment. We hypothesized that combination of CRT and pembrolizumab can lead to further increase in TILs and their activation. Methods: Patients with resectable or borderline resectable PC have been randomized 2:1 to the investigational treatment (Arm A) to receive pembrolizumab 200mg IV every 3 weeks on days 1, 22, and 43 during concurrent CRT with capecitabine (825 mg/m2 orally twice daily, Monday-Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days) or Arm B to receive only concurrent CRT with capecitabine. Restaging CT scan or MRI is performed at 4-6 weeks after completion of neoadjuvant treatment, and patients with resectable disease will undergo surgical resection. Here we report the preliminary safety data based on 22 enrolled patients. Results: As of February 3-2017,22 patients have been enrolled (14 Arm A and 8 Arm B). 50% of the patients had resectable disease (7 arm A; 4 arm B) and the other 50% had borderline resectable disease (7 Arm A; 4 arm B). Post-neoadjuvant therapy, 6 patients had unresectable disease (3 on each arm), and 14 patients underwent surgery (10 arm A and 4 arm B). There were 7 grade 3 treatment-related toxicities in Arm A (5 patients): 2 grade 3 diarrhea attributed to CRT; 4 grade 3 lymphopenias attributed to pembrolizumab, CRT or the combination; and one patient had elevated alkaline phosphatase probably related to the combination that met the definition of DLT and resolved after holding the treatment and receiving steroids. There was only one grade 3 toxicity on Arm B: lymphopenia attributed to CRT. No grade 4 toxicities have been reported on either arm. There were no major surgical complications reported within 30 days post-surgery. Conclusions: The combination of CRT and pembrolizuamb is safe based on the presented data. Clinical trial information: NCT02305186.

scholarly journals 960 Randomized multicenter study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1010-A1010
Author(s):  
Osama Rahma ◽  
Mathew Katz ◽  
Todd Bauer ◽  
Brian Wolpin ◽  
Chee-Chee Stucky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Immune Cell ◽  
Neoadjuvant Chemoradiation ◽  
Cancer Center ◽  
Functional Responses ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable

BackgroundPancreatic cancer (PC) is a challenging target for immunotherapy due to its immune-suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of tumor-infiltrating lymphocytes (TILs). We hypothesized that the combination of CRT and pembrolizumab can further expand and activate TILs.MethodsPatients with resectable or borderline resectable PC were randomized 2:1 to the investigational treatment (Arm A) of pembrolizumab 200mg IV every 3 weeks concurrently with CRT (capecitabine 825 mg/m2 orally twice daily and radiation 50.4 Gy in 28 fractions over 28 days) or CRT only (Arm B) prior to surgical resection. The primary endpoints were safety and difference in TILs density between Arm A and B assessed using multiplexed immunofluorescence on resected tumor specimens. As a correlate analysis, single cell RNA-sequencing (scRNA-seq) was performed to quantify gene expression in T cells from tumors and peripheral blood, and to track expanded T cell clonotypes in these compartments (n=4 patients Arm A; n=3 patients Arm B). The study was amended after enrollment of 37 patients to allow FOLFIRINOX prior to CRT, given changes in standard of care.Results37 patients were enrolled (24 Arm A, 13 Arm B). After neoadjuvant therapy, 13 patients had unresectable disease (9 on A, 4 on B), and 24 patients underwent surgery and were evaluable for the TILs primary endpoint (17 arm A, 7 arm B). The mean difference (A-B) in CD8+ T cell density was 36 cells/mm2 (95% CI -85 to 157, stdev 130) (p 0.48). Additional analysis did not show significant differences in activated cytotoxic T cells, regulatory T cells, M1- or M2-like polarized macrophages, or granulocytes. The median recurrence free survival (RFS) was 18.2 months on Arm A and 14.1 on Arm B (p 0.41). Overall survival was 27.8 months on Arm A and 24.3 on Arm B (p 0.68) with a median follow up of 2.2 years. The most common grade 3 treatment-related toxicities were lymphopenia reported in 29% on Arm A and 31% on Arm B, respectively followed by diarrhea in 8% on Arm A attributed to CRT. scRNA-seq revealed clonal expansion and expression of co-inhibitory markers among TIL subsets.ConclusionsThe combination of CRT and pembrolizumab is safe. Preliminary analysis shows that the addition of pembrolizumab to CRT has minimal effects on intratumoral densities of TILs and other immune cell populations. Single cell transcriptome analyses enable in-depth characterization of the functional responses of T cells to pembrolizumab in the setting of CRT.AcknowledgementsThis study was funded by MerckTrial RegistrationNCT02305186Ethics ApprovalThe study was conducted at 6 sites: University of Virginia, Dana Farber Cancer Institute, MD Anderson Cancer Center (MDACC), Mayo Clinic, Hartford Healthcare Cancer Center, and University of Miami. Written informed consent was provided by the study participants and the protocol was approved by the relevant local IRBs in each site.

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