McClaine RJ, Lowy AM, Sussman JJ, et al. Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer

Department of Surgery, University of Cincinnati Medical Center, 234 Goodman Street, Cincinnati, OH 45219, USA.
HPB (Impact Factor: 2.68). 02/2010; 12(1):73-9. DOI: 10.1111/j.1477-2574.2009.00136.x
Source: PubMed


Borderline resectable pancreatic cancers are technically amenable to surgical resection, but are associated with increased risk of locoregional recurrence. Patients with these tumours may be treated with neoadjuvant therapy in an attempt to improve margin-negative resection rates.
The University of Cincinnati Pancreatic Cancer Database was retrospectively reviewed. Borderline resectable disease was defined by the following radiographic criteria: (i) short segment occlusion of the superior mesenteric vein (SMV), portal vein (PV) or SMV/PV confluence; (ii) short segment hepatic artery encasement, or (iii) superior mesenteric artery/coeliac artery abutment of <180 degrees. Patients with resectable disease who had questionable metastatic disease or poor performance status were also included.
Twenty-nine patients met the criteria. Of these, 26 underwent a full course of neoadjuvant therapy. Twelve (46%) underwent surgical resection and 14 had tumour progression or were deemed unresectable at laparotomy. The most common neoadjuvant therapy regimen was gemcitabine-based chemotherapy alone (58%). Of those undergoing surgery, 67% had margin-negative (R0) resections and 42% required venous resection. Median survival was 15.5 months for unresected patients and 23.3 months for resected patients.
Borderline resectable pancreatic tumours can be treated neoadjuvantly, resulting in margin-negative resection and survival rates similar to those in initially resectable disease.

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    • "McClaine et al. reported a 46% rate of surgical resection in a cohort of 26 patients with borderline pancreatic adenocarcinoma who underwent neoadjuvant chemoradiotherapy; 67% of them had a margin free resection. Median survival for resected patients was 23.3 months vs. 15.5 months for non-resected cases [12]. These two studies included a different number of patients; however, the difference was statistically significant in both. "
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    ABSTRACT: Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.
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    ABSTRACT: Facilitation of margin-negative resection is the goal of neoadjuvant therapy regimens used in the treatment of borderline-resectable pancreatic cancer patients. Multiple treatment approaches have shown efficacy in this setting, including neoadjuvant GTX (gemcitabine [Gemzar], docetaxel [Taxotere], and capecitabine [Xeloda]) and radiotherapy (RT). Three-dimensional tumor response may be a more accurate method of assessment compared to traditional 1- and 2-dimensional techniques. We compared these 3 methods in a series of patients who underwent neoadjuvant GTX-RT and surgical resection. This retrospective review included borderline-resectable pancreatic cancer patients treated with neoadjuvant GTX followed by 5-FU chemoradiotherapy with the intent of downstaging to resectability. Tumor was contoured on computed tomography (CT) scans obtained at the following time points: (A) initial staging, (B) CT simulation, and (C) restaging. These contours were used to determine tumor response according to WHO, RECIST, and volumetric criteria. Fourteen patients all experienced a measurable decrease in tumor volume following neoadjuvant therapy and were deemed suitable for at least surgical exploration. Radiotherapy was delivered to a median 50 Gy (range, 45-52 Gy) in 1.8-2.0 Gy fractions via 3-D conformal (21%) or IMRT (79%). The median percent volume changes before and after CT simulation were -3.4% and -52.6%, respectively. The overall median percent change was -54.5%. The corresponding absolute volume changes were -0.42 cm(3) (range, 9.12 to -12.47), -5.31 cm(3) (range, 2.06 to -15.93), and -6.72 cm(3) (range, 0.53 to -15.47), respectively. Response according to WHO, RECIST, and volumetric methods was identical with the exception of 1 patient. This is the first study to quantify volumetric tumor change objectively as a result of neoadjuvant chemoradiotherapy for the treatment of borderline resectable pancreatic cancer. Our data suggest that tumor response to neoadjuvant therapy is essentially equivalent between 1-, 2-, and 3-dimensional assessment methods.
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    ABSTRACT: Neoadjuvant treatment frequently is performed in unresectable/borderline resectable pancreatic cancer. The aim of this study was to retrospectively compare postoperative outcomes and survival of patients who underwent pancreatectomy after neoadjuvant treatment for locally advanced/borderline resectable pancreatic cancer (neoadjuvant treatment group) with those of patients with resectable disease who underwent upfront surgery. Between 2000 and 2008, there were 403 patients who underwent pancreatic cancer resection, 41 (10.1%) patients after neoadjuvant treatment for initially unresectable tumors and 362 (89.9%) patients had upfront surgery. Univariate and multivariable analyses were performed. Mortality/morbidity rates were similar in the 2 groups. Nodal metastases were significantly lower in the neoadjuvant treatment group (31.7% vs 86.2%; P < .001). A complete pathologic response was observed in 13.6% after neoadjuvant treatment. Median disease-specific survival from resection was 35 and 27 months in the neoadjuvant treatment and upfront groups, respectively (P = .74). In the neoadjuvant treatment group survival rates were similar in N0/N1 patients. Postoperative mortality and morbidity do not significantly increase after neoadjuvant treatment. Neoadjuvant treatment in locally advanced pancreatic cancer can lead to an objective pathologic response, but this does not significantly improve survival after resection.
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