LETTER TO Preoperative Gemcitabine-based Chemoradiation Therapy for Resectable and Borderline Resectable Pancreatic Cancer To the Editor: e congratulate the authors not only for their brilliant results but also for highlighting the role of neoadjuvant treatment in the management of patients with pancreatic cancer. The potential benefit of preoperative chemoradiation with or without induction chemotherapy has been long recognized but is commonly avoided in the treatment of resectable lesions because of the potential risk of tumor progression. On the contrary, the borderline resectable group offers a great opportunity to investigate the value of neoadjuvant modalities as the ideal management of these patients is still unknown, differs across the world, and, most importantly, the definition of this condition remains controversial. In this study, the authors applied similar criteria to those suggested by the MD Anderson group in 2006,1 but the resectability status was defined exclusively by the relationship between the arterial structures and the tumor. In particular, only those patients with limited arterial involvement (no more than 180 degrees of circumferential abutment of the vessel) were considered borderline resectable. Ultimately, 54% of patients in the borderlineresectable group were resected after neoadjuvant chemoradiation and a documented, still not necessarily significant, tumor response.2 Indeed, pancreatic cancer is associated with intense stromal reaction and fibrosis, which rarely results in sufficient downstaging to restore a normal tissue plane between the artery and the tumor. It is therefore surprising that only 3 patients in this group required reconstruction of the common hepatic artery.2 As such, it is difficult to reconcile this with an astonishing R0 rate of 98%, even after considering the variation in histopathological reporting across different units, due to the lack of standardization of sampling and processing of periampullary tumors.3 Second, a 34% 5-year survival in this group is a remarkable achievement in support of neoadjuvant chemoradiation.2 It further reiterates that surgical resection is essential
W
Disclosure: The authors declare no conflicts of interest. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000000685
THE
EDITOR
in providing long-term survival. En bloc arterial resection has been successfully and safely performed in high-volume centers, but its value in providing a survival benefit is uncertain. The results of this study should therefore represent a good platform to consider arterial resection and reconstruction in patients where the tumor is not separable from the artery and who have successfully received neoadjuvant treatment. If we are genuinely moving to a more aggressive approach to treat borderline-resectable tumors, and as suggested by Mollberg et al4 in a meta-analysis of arterial resection for pancreatic cancer, we should consider instituting a registry to prospectively assess the surgical and oncological outcomes of patients whose management has until today been considered controversial.
Reena Ravikumar, MBChB, MRCS (Eng) Giuseppe Fusai, MS, FRCS Department of HPB and Liver Transplant Surgery Royal Free London Hospital London, UK [email protected]
REFERENCES 1. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13:1035–1046. 2. Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258:1040– 1050. 3. Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford). 2009;11:282–289. 4. Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254:882–893.
Reply: y colleagues and I appreciate the comments and interest that Drs Ravikumar and Fusai have shown in our article.1 I would like to respond to their comments on behalf of our authors. First, the authors commented on the low frequency we observed (n ¼ 3) of resection and reconstruction of the common hepatic artery (CHA) during the surgery after preoperative chemoradiation therapy (CRT) for borderline resectable pancreatic cancer (PC-BR). There are several potential explanations for this issue. According to the resectability status criteria
M
Disclosure: The authors declare no conflicts of interest. DOI: 10.1097/SLA.0000000000000684
Annals of Surgery Volume 262, Number 6, December 2015
from the MD Anderson Cancer Center group,2 a tumor with abutment or encasement of a short segment of the CHA is included in PC-BR, whereas in our study, a tumor with an abutment less than 180 degrees of the circumference of the CHA was included in PC-BR, and a tumor showing even a short segment of encasement of the CHA was excluded from our study (described in ‘‘Methods-Definition of the Resectability Status’’ in our article).1 Moreover, we also employed a relatively conservative policy for proceeding to laparotomy after the completion of preoperative CRT in PC-BR cases; that is, PC-BR cases were submitted to a subsequent surgery only when the tumors showed at least modest regression of the tumor-arterial abutment according to radiographical examination at the completion of preoperative CRT [but not necessarily enough to qualify as a partial response according to the Response Evaluation Criteria in Solid Tumors (described in ‘‘Methods-Protocol for Preoperative Gemcitabine-Based CRT and Procedures for Subsequent Surgery’’ in our article)].1 Under these conditions, among the 52 PCBR patients who underwent laparotomy after preoperative CRT, 4 patients avoided subsequent surgery because of the presence of local disease during the laparotomy, and among them, 1 patient did not undergo pancreatectomy because of tumor invasion that extended from the root of the CHA to the proper hepatic artery (bifurcation of the right and left hepatic artery). Among the 43 patients who successfully received subsequent surgery after preoperative CRT, preoperative radiographical examination revealed tumor abutment to the CHA in 17 cases: 11 cases of pancreatic head cancer and 6 cases of pancreatic body cancer. In 9 of the 11 cases of pancreatic head cancer, we successfully separated the CHA from the tumors, whereas resection and reconstruction of the hepatic artery was required in the remaining 2 cases. In 4 of the 6 cases of pancreatic body cancer, we performed distal pancreatectomy with en bloc celiac axis resection (DP-CAR),3 whereas we successfully separated the CHA from the tumors and preserved the celiac axis and CHA in the other 2 cases. One patient who received DP-CAR required reconstruction of the hepatic artery. Therefore, 6 (2 with pancreatic head cancer and 4 with pancreatic body cancer) among the 17 patients with PC-BR whose tumor abutment of the CHAwas shown by preoperative radiography required resection of the hepatic artery, and among these, 3 required reconstruction of the hepatic artery. In addition, in previous reports describing preoperative CRT for PC-BR, the frequency of resection and reconstruction of the CHA is not necessarily high. Katz et al4 reported that resection of the CHAwas performed in 2 of 32 patients with PC-BR after preoperative CRT, www.annalsofsurgery.com | e103
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
W
Disclosure: The authors declare no conflicts of interest. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000000685
THE
EDITOR
in providing long-term survival. En bloc arterial resection has been successfully and safely performed in high-volume centers, but its value in providing a survival benefit is uncertain. The results of this study should therefore represent a good platform to consider arterial resection and reconstruction in patients where the tumor is not separable from the artery and who have successfully received neoadjuvant treatment. If we are genuinely moving to a more aggressive approach to treat borderline-resectable tumors, and as suggested by Mollberg et al4 in a meta-analysis of arterial resection for pancreatic cancer, we should consider instituting a registry to prospectively assess the surgical and oncological outcomes of patients whose management has until today been considered controversial.
Reena Ravikumar, MBChB, MRCS (Eng) Giuseppe Fusai, MS, FRCS Department of HPB and Liver Transplant Surgery Royal Free London Hospital London, UK [email protected]
REFERENCES 1. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13:1035–1046. 2. Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258:1040– 1050. 3. Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford). 2009;11:282–289. 4. Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254:882–893.
Reply: y colleagues and I appreciate the comments and interest that Drs Ravikumar and Fusai have shown in our article.1 I would like to respond to their comments on behalf of our authors. First, the authors commented on the low frequency we observed (n ¼ 3) of resection and reconstruction of the common hepatic artery (CHA) during the surgery after preoperative chemoradiation therapy (CRT) for borderline resectable pancreatic cancer (PC-BR). There are several potential explanations for this issue. According to the resectability status criteria
M
Disclosure: The authors declare no conflicts of interest. DOI: 10.1097/SLA.0000000000000684
Annals of Surgery Volume 262, Number 6, December 2015
from the MD Anderson Cancer Center group,2 a tumor with abutment or encasement of a short segment of the CHA is included in PC-BR, whereas in our study, a tumor with an abutment less than 180 degrees of the circumference of the CHA was included in PC-BR, and a tumor showing even a short segment of encasement of the CHA was excluded from our study (described in ‘‘Methods-Definition of the Resectability Status’’ in our article).1 Moreover, we also employed a relatively conservative policy for proceeding to laparotomy after the completion of preoperative CRT in PC-BR cases; that is, PC-BR cases were submitted to a subsequent surgery only when the tumors showed at least modest regression of the tumor-arterial abutment according to radiographical examination at the completion of preoperative CRT [but not necessarily enough to qualify as a partial response according to the Response Evaluation Criteria in Solid Tumors (described in ‘‘Methods-Protocol for Preoperative Gemcitabine-Based CRT and Procedures for Subsequent Surgery’’ in our article)].1 Under these conditions, among the 52 PCBR patients who underwent laparotomy after preoperative CRT, 4 patients avoided subsequent surgery because of the presence of local disease during the laparotomy, and among them, 1 patient did not undergo pancreatectomy because of tumor invasion that extended from the root of the CHA to the proper hepatic artery (bifurcation of the right and left hepatic artery). Among the 43 patients who successfully received subsequent surgery after preoperative CRT, preoperative radiographical examination revealed tumor abutment to the CHA in 17 cases: 11 cases of pancreatic head cancer and 6 cases of pancreatic body cancer. In 9 of the 11 cases of pancreatic head cancer, we successfully separated the CHA from the tumors, whereas resection and reconstruction of the hepatic artery was required in the remaining 2 cases. In 4 of the 6 cases of pancreatic body cancer, we performed distal pancreatectomy with en bloc celiac axis resection (DP-CAR),3 whereas we successfully separated the CHA from the tumors and preserved the celiac axis and CHA in the other 2 cases. One patient who received DP-CAR required reconstruction of the hepatic artery. Therefore, 6 (2 with pancreatic head cancer and 4 with pancreatic body cancer) among the 17 patients with PC-BR whose tumor abutment of the CHAwas shown by preoperative radiography required resection of the hepatic artery, and among these, 3 required reconstruction of the hepatic artery. In addition, in previous reports describing preoperative CRT for PC-BR, the frequency of resection and reconstruction of the CHA is not necessarily high. Katz et al4 reported that resection of the CHAwas performed in 2 of 32 patients with PC-BR after preoperative CRT, www.annalsofsurgery.com | e103
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
