Surgery Improves Survival After Neoadjuvant Therapy for Borderline and Locally Advanced Pancreatic Cancer: A Single Institution Experience.
Adenocarcinoma
/ drug therapy
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Combined Modality Therapy
Female
Fluorouracil
Humans
Irinotecan
Leucovorin
Male
Middle Aged
Neoadjuvant Therapy
Oxaliplatin
Pancreatectomy
Pancreatic Neoplasms
/ drug therapy
Retrospective Studies
Survival Rate
Sweden
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
pubmed:
5
4
2019
medline:
11
3
2021
entrez:
5
4
2019
Statut:
ppublish
Résumé
Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated. A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017. Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival. All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection.
Sections du résumé
OBJECTIVE
Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC).
SUMMARY BACKGROUND DATA
It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated.
METHODS
A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017.
RESULTS
Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival.
CONCLUSIONS
All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection.
Identifiants
pubmed: 30946073
pii: 00000658-202103000-00027
doi: 10.1097/SLA.0000000000003301
doi:
Substances chimiques
folfirinox
0
Oxaliplatin
04ZR38536J
Irinotecan
7673326042
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
579-586Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Hartwig W, Werner J, Jäger D, et al. Improvement of surgical results for pancreatic cancer. Lancet Oncol 2013; 14:e476–485.
Sun H, Ma H, Hong G, et al. Survival improvements in patients with pancreatic cancer by decade: a period analysis of the SEER database, 1981–2010. Sci Rep 2014; 4:1–10. 6747.
Neoptolemos JP, Stocken DD, Friess H, et al. European Study Group for Pancreatic Cancer. A randomised trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Eng J Med 2004; 350:1200–1210.
Neoptolemos JP, Moore MJ, Cox TF, et al. European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA 2012; 308:147–156.
Neoptolemos JP, Palmer DH, Ghaneh P, et al. European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomized, phase 3 trial. Lancet 2017; 389:1011–1024.
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013; 310:1473–1481.
Ueno H, Kosuge T, Matsuyama Y, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer 2009; 101:908–915.
Conroy T, Desseigne F, Ychou M, et al. for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Eng J Med 2011; 364:1817–1825.
Mahaseth H, Brutcher E, Kauh J, et al. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 2013; 42:1311–1315.
Boone BA, Steve J, Krasinskas AM, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol 2013; 108:236–241.
Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicentre prospective observational cohort. Ann Surg Oncol 2015; 22:295–301.
Sadot E, Doussot A, O’Reilly EM, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol 2015; 22:3512–3521.
Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 2016; 17:801–810.
Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol 2015; 22:1153–1159.
Gemenetzis G, Groot VP, Blair AB, et al. Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection. Ann Surg 2018.
Michelakos T, Pergolini I, Fernández-Del Castillo C, et al. Predictors of respectability and survival in patients with borderline and locally advanced pancreatic cancer who underwent neoadjuvant treatment with FOLFIRINOX. Ann Surg 2017.
Hacket T, Sachsenmaier M, Hinz U, et al. Locally advanced pancreatic cancer. Neoadjuvant therapy with FOLFIRINOX results in resectability in 60% of the patients. Ann Surg 2016; 264:457–463.
van Veldhuisen E, Vogel JA, Klopmaker S, et al. Added value of Ca 19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. HPB 2018; 20:605–611.
Petrelli F, Coinu A, Borgonovo K. et al, on behalf of Gruppo Italiano per lo Studio dei carcinoma dell’Apparato Digerente (GISCAD). FOLFIRINOX-based neoadjuvant therapy in borderline-resectable or unresectable pancreatic cancer. Pancreas 2015; 44:515–521.
Ferrone C, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 2015; 261:12–17.
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Eng J Med 2013; 369:1691–1703.
Chin V, Nagrial A, Sjoquist K, et al. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Review 2018; 3:CD011044.
Kim S, Signorovich JE, Yang H, et al. Comparative effectiveness of nab-paclitaxel plus gemcitabine vs FOLFIRINOX in metastatic pancreatic cancer: a retrospective nationwide chart review in the United States. Adv Ther 2018; 35:1564–1577.
Peterson SL, Husnain M, Pollack T, et al. Neoadjuvant Nab-paclitaxel and gemcitabine in borderline resectable and unresectable pancreatic adenocarcinoma in patients who are ineligible for FOLFIRINOX. Anticancer Res 2018; 38:4035–4039.
Habermehl D, Kessel K, Welzel T, et al. Neoadjuvant chemoradiation with gemcitabine for locally advanced pancreatic cancer. Radiat Oncol 2012; 7:28.
Papavasiliou P, Hoffman JP. Cohen et al. Impact of preoperative therapy on patterns of recurrence in pancreatic cancer. HPB (Oxford) 2014; 16:34–39.
Schorn S, Demir IE, Samm N, et al. Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma. BJS Open 2018; 2:52–61.
Verbeke C, Häberle L, Lenggenhager D, et al. Pathology assessment of pancreatic cancer following neoadjuvant treatment: time to move on. Pancreatology 2018; 18:467–476.
Lee SM, Katz MHG, Liu L, et al. Validation of a proposed tumor regression grading scheme for pancreatic ductal adenocarcinoma after neoadjuvant therapy as a prognostic indicator of survival. Am J Surg Pathol 2016; 40:1653–1660.
Vechiarelli S, Machini M, Grassi E, et al. Comparing recist and Choi's criteria to evaluate radiological response to chemotherapy in patients with advanced pancreatic cancer. J Clin Oncol 2013; 31: (15 Suppl.): e15069.
Bockhorn M, Uzunoglu FG, Adham M. et al, for the International Study Group of Pancreatic Surgery. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2014; 155:977–988.
Shrikhande SV, Kleef J, Reiser C, et al. Pancreatic resection for M1 pancreatic ductal adenocarcinoma. Ann Surg Oncol 2007; 14:118–127.
Del Chiaro M, Segersvärd R, Rangelova E, et al. Cattel-Braasch maneuver combined with artery-first approach for superior mesenteric-portal vein resection during pancreatectomy. J Gastrointest Surg 2015; 19:2264–2268.
Zhou Y, Zhang Z, Liu Y, et al. Pancreatectomy combined with superior mesenteric-portal vein resection for pancreatic cancer: a meta-analysis. World J Surg 2012; 36:884–891.
Kleive D, Sahakyan MA, Berstad AE, et al. Trends in indications, complications and outcomes for venous resection during pancreaticoduodenectomy. Br J Surg 2017; 104:1558–1567.
Malleo G, Maggino L, Marchegiani G, et al. Pancreatectomy with venous resection for pT3 head adenocarcinoma: perioperative outcomes, recurrence pattern and prognostic implications of histologically confirmed vascular infiltration. Pancreatology 2017; 17:847–857.
Boggi U, Del Chiaro M, Croce C, et al. Prognostic implications of tumor invasion or adhesion to peripancreatic vessels in resected pancreatic cancer. Surgery 2009; 146:869–881.
Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systemic review and meta-analysis. Ann Surg 2011; 254:882–893.
Del Chiaro M, Rangelova E, Halimi A, et al. Pancreatectomy with arterial resection is superior to palliation in patients with borderline resectable or locally advanced pancreatic cancer. HPB (Oxford) 2018; 21:219–225.
Westermark S, Rangelova E, Ansorge C, et al. Cattell-Braasch maneuver combined with local hypothermia during superior mesenteric artery resection in pancreatectomy. Langenbecks Arch Surg 2016; 401:1241–1247.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Pancreatic adenocarcinoma (Version2.2018). Available at: NCCN.org. Accessed July 10, 2018.
Evans DB, Farnell MB, Lillemoe KD, et al. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009; 16:1736–1744.
von Elm E, Altman DG, Egger M, et al. STROBE Initiative Int J Surg 2014; 12:1495–1499.
Isaji S, Mizuno S, Windsor JA, et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma. Pancreatology 2018; 18:2–11.
Tamburrino D, Partelli S, Crippa S, et al. Selection criteria in resectable pancreatic cancer: a biological and morphological approach. World J Gastroenterol 2014; 20:11210–11215.