17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The borderline resectable/locally advanced pancreatic ductal adenocarcinoma: What should be the surgeon's choice?

      article-commentary
      ,
      Endoscopic Ultrasound
      Medknow Publications & Media Pvt Ltd

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          INTRODUCTION In 2006, MD Anderson group published a new classification of pancreatic ductal adenocarcinoma (PDAC) that took into account the degree of neoplastic involvement of peripancreatic vessels.[1] According to that, PDAC was classified as resectable, borderline resectable (BR), or locally advanced (LA).[1] From its introduction, this classification has been universally adopted, allowing a standardization of terminology used by different pancreatic centers. If, in case of resectable PDAC, upfront radical surgery followed by adjuvant chemotherapy is the gold standard treatment,[2] on the other hand, the optimal treatment strategy of patients with BR and LA-PDAC is complex, and it is still matter of debate. BORDERLINE RESECTABLE PANCREATIC CANCER BR-PDAC is defined as a tumor with abutment, encasement, or occlusion of superior mesenteric vein or portal vein, abutment of superior mesenteric artery (SMA) <180°, and abutment or short segment encasement of common hepatic artery.[1] Two questions about the optimal treatment for BR-PDAC are still open: Is it oncologically more effective to perform an upfront surgery followed by adjuvant treatment or a neoadjuvant treatment followed by radical surgery? In case of neoadjuvant treatment, what is the best strategy to adopt (chemotherapy, radiochemotherapy, chemotherapy + radiochemotherapy)? The adoption of a neoadjuvant protocol treatment followed by radical surgery for BR-PDAC has some theoretical advantages: (a) early treatment of micrometastatic disease; (b) selection of patients with localized disease and more favorable tumor biology, who are most likely to benefit from surgical resection; and (c) increased likelihood of an R0 resection. In the last decade, many retrospective studies evaluating the results of neoadjuvant treatments followed by radical surgery for BR-PDAC have been published.[3 4 5] In 2008, Katz et al.[4] evaluated 160 patients with BR-PDAC: 78% of them completed the neoadjuvant protocol, and 41% of them underwent pancreaticoduodenectomy. R0 resection was obtained in 94% of resected cases. Median survival was 40 months for patients who underwent preoperative therapy followed by surgery and 13 months for patients who did not undergo pancreaticoduodenectomy (P < 0.001). This study, as others published in the last years, demonstrated that the neoadjuvant approach allowed for the identification of a subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group. According to these results, even in the absence of randomized controlled trials, the trend of many pancreatic surgeons during the last years has been to adopt a neoadjuvant approach for patients affected by BR-PDAC. The debate on the most effective neoadjuvant treatment scheme is currently unsolved. Conventionally, chemoradiation for BR-PDAC with gemcitabine- or 5-fluorouracil-based protocols along with radiotherapy has been adopted,[6] showing resection rates of approximately 30%.[7] With the introduction of other regimens, such as FOLFIRINOX or nab-paclitaxel,[8 9 10 11] resection rates of up to 60% were achieved. Unfortunately, there are no randomized studies comparing these approaches, and consequently, evidence-based recommendations on the best treatment option cannot be given. However, a FOLFIRINOX-based regimen seems to be the most promising approach. LOCALLY ADVANCED PANCREATIC CANCER LA-PDAC is defined as a tumor with >180° abutment or encasement of the SMA, long segment common hepatic artery abutment, and encasement of the celiac axis as well as a nonreconstructible portal vein/superior mesenteric vein.[1] For many years, LA-PDAC has been considered an unresectable disease, and gemcitabine monotherapy (sometimes combined with radiotherapy) has been the standard palliative treatment.[12] In the last years, the advent of more effective chemotherapeutic agents and the skills of the surgeons to perform arterial resections during pancreatectomy led to a change of this approach. Recently, the superiority of FOLFIRINOX over gemcitabine monotherapy in patients with metastatic pancreatic cancer was demonstrated.[13] The comparable poor prognosis of LA-PDAC and the lack of beneficial therapies have also led to the administration of FOLFIRINOX, sometimes combined with radiotherapy, in these subset of patients. A systematic review on clinical outcomes after FOLFIRINOX-based treatment for LA-PDAC demonstrated a 28% resection rate, of which 77% were R0, and a median overall survival ranging between 8.9 and 25.0 months.[14] These data suggest that FOLFIRINOX-based treatment is indeed a promising option for patients with LA-PDAC, with acceptable toxicity (23% Grade 3–4 complications). Future unselected prospective cohort studies are needed to determine the exact role for FOLFIRINOX in LA-PDAC. The increasing rate of resection after neoadjuvant treatment for LA-PDAC is also a consequence of a more aggressive surgical attitude. In the last years, many studies reporting the experience with arterial resection during pancreatectomy have been published. However, the benefit of this kind of approach is still questionable according to the available literature. Published series of arterial resections during pancreaticoduodenectomy are small, often including heterogeneous anatomical reconstructions.[15 16] Such studies reported a not negligible morbidity and mortality, perhaps countering any potential oncologic benefits.[16] CONCLUSIONS BR-PDAC represents an interdisciplinary treatment challenge. Recent literature focuses on the utility of neoadjuvant treatment in this subset of cases, to obtain better oncological results. LA-PDAC was previously thought not to be amenable to surgery. However, the evolution of vascular reconstruction techniques combined with administration of active neoadjuvant therapy has allowed for the conversion of some cases to potentially resectable disease.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          Borderline resectable pancreatic cancer: the importance of this emerging stage of disease.

          Patients with borderline resectable pancreatic adenocarcinoma (PA) include those with localized disease who have tumor or patient characteristics that preclude immediate surgery. There is no optimal treatment schema for this distinct stage of disease, so the role of surgery is undefined. We defined patients with borderline resectable PA as fitting into one of three distinct groups. Group A comprised patients with tumor abutment of the visceral arteries or short-segment occlusion of the Superior Mesenteric Vein. In group B, patients had findings suggestive but not diagnostic of metastasis. Group C patients were of marginal performance status. Patients were treated initially with chemotherapy, chemoradiation, or both; those of sufficient performance status who completed preoperative therapy without disease progression were considered for surgery. Between October 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy (< 50% viable tumor) was seen in 37 (56%) of 66 patients. Median survival was 40 months for the 66 patients who completed all therapy and 13 months for the 94 patients who did not undergo pancreatectomy (p < 0.001). This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy.

            With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of "borderline resectability." In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer

              Background FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. Methods The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. Results Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3–4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3–4 toxicity. Conclusions Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.
                Bookmark

                Author and article information

                Journal
                Endosc Ultrasound
                Endosc Ultrasound
                EUS
                Endoscopic Ultrasound
                Medknow Publications & Media Pvt Ltd (India )
                2303-9027
                2226-7190
                December 2017
                : 6
                : Suppl 3
                : S87-S89
                Affiliations
                [1]Pancreatic Surgery, Humanitas University, Humanitas Research Hospital, Rozzano MI, Italy
                Author notes
                Address for correspondence Dr. Alessandro Zerbi, Humanitas University, Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano MI, Italy. E-mail: alessandro.zerbi@ 123456hunimed.eu
                Article
                EUS-6-87
                10.4103/eus.eus_69_17
                5774082
                f5c12aa2-1852-4acc-a784-d7f2f7c3c833
                Copyright: © 2017 Spring Media Publishing Co. Ltd

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 12 July 2017
                : 31 August 2017
                Categories
                Commentary

                Comments

                Comment on this article