Predictors, Patterns, and Timing of Recurrence Provide Insight into the Disease Biology of Invasive Carcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms.


Journal

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
ISSN: 1873-4626
Titre abrégé: J Gastrointest Surg
Pays: United States
ID NLM: 9706084

Informations de publication

Date de publication:
11 2022
Historique:
received: 27 04 2022
accepted: 10 07 2022
pubmed: 2 8 2022
medline: 11 11 2022
entrez: 1 8 2022
Statut: ppublish

Résumé

To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN. Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized. Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively. Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7-30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06-8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12-4.60); and N2, HR: 5.67 95%CI (2.93-10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04-13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14-6.21)] emerged as independent predictors. The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner.

Sections du résumé

OBJECTIVES
To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN.
BACKGROUND
Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized.
METHODS
Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively.
RESULTS
Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7-30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06-8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12-4.60); and N2, HR: 5.67 95%CI (2.93-10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04-13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14-6.21)] emerged as independent predictors.
CONCLUSIONS
The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner.

Identifiants

pubmed: 35915375
doi: 10.1007/s11605-022-05428-4
pii: 10.1007/s11605-022-05428-4
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2311-2320

Subventions

Organisme : German Research Foundation
ID : KI 2437/2-1

Informations de copyright

© 2022. The Society for Surgery of the Alimentary Tract.

Références

Kromrey ML, Bülow R, Hübner J, et al. Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut. 2018;67(1):138-145.
doi: 10.1136/gutjnl-2016-313127 pubmed: 28877981
van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol. 2019;16(11):676-689.
doi: 10.1038/s41575-019-0195-x pubmed: 31527862
Adsay V, Mino-Kenudson M, Furukawa T, et al. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. Ann Surg. 2016;263(1):162-177. https://doi.org/10.1097/SLA.0000000000001173
doi: 10.1097/SLA.0000000000001173 pubmed: 25775066
Tanaka M, Fernández-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12(3):183-197. https://doi.org/10.1016/j.pan.2012.04.004
doi: 10.1016/j.pan.2012.04.004 pubmed: 22687371
[5] Tanaka M, Fernández-Del Castillo C, Kamisawa T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17(5):738-753. doi: https://doi.org/10.1016/j.pan.2017.07.007
doi: 10.1016/j.pan.2017.07.007 pubmed: 28735806
Aronsson L, Andersson R, Ansari D. Intraductal papillary mucinous neoplasm of the pancreas - epidemiology, risk factors, diagnosis, and management. Scand J Gastroenterol. 2017;52(8):803-815. https://doi.org/10.1080/00365521.2017.1318948
doi: 10.1080/00365521.2017.1318948 pubmed: 28446039
Mino-Kenudson M, Fernández-del Castillo C, Baba Y, et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut. 2011;60(12):1712-1720. https://doi.org/10.1136/gut.2010.232272
doi: 10.1136/gut.2010.232272 pubmed: 21508421
Waters JA, Schnelldorfer T, Aguilar-Saavedra JR, et al. Survival after resection for invasive intraductal papillary mucinous neoplasm and for pancreatic adenocarcinoma: a multi-institutional comparison according to American Joint Committee on Cancer Stage. J Am Coll Surg. 2011;213(2):275-283. https://doi.org/10.1016/j.jamcollsurg.2011.04.003
doi: 10.1016/j.jamcollsurg.2011.04.003 pubmed: 21601488
Marchegiani G, Andrianello S, Dal Borgo C, et al. Adjuvant chemotherapy is associated with improved postoperative survival in specific subtypes of invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas: it is time for randomized controlled data. HPB (Oxford). 2019;21(5):596-603. https://doi.org/10.1016/j.hpb.2018.09.013
doi: 10.1016/j.hpb.2018.09.013 pubmed: 30366881
Caponi S, Vasile E, Funel N, et al. Adjuvant chemotherapy seems beneficial for invasive intraductal papillary mucinous neoplasms. Eur J Surg Oncol. 2013;39(4):396-403. https://doi.org/10.1016/j.ejso.2012.12.005
doi: 10.1016/j.ejso.2012.12.005 pubmed: 23290583
Turrini O, Waters JA, Schnelldorfer T, et al. Invasive intraductal papillary mucinous neoplasm: predictors of survival and role of adjuvant therapy. HPB (Oxford). 2010;12(7):447-455. https://doi.org/10.1111/j.1477-2574.2010.00196.x
doi: 10.1111/j.1477-2574.2010.00196.x pubmed: 20815853 pmcid: 3030753
McMillan MT, Lewis RS, Drebin JA, et al. The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN). Cancer. 2016;122(4):521-533. https://doi.org/10.1002/cncr.29803
doi: 10.1002/cncr.29803 pubmed: 26587698
Mungo B, Croce C, Oba A, et al. Controversial Role of Adjuvant Therapy in Node-Negative Invasive Intraductal Papillary Mucinous Neoplasm [published online ahead of print, 2020 Aug 2]. Ann Surg Oncol. 2020; https://doi.org/10.1245/s10434-020-08916-6
Amini N, Habib JR, Blair A, et al. Invasive and Non-Invasive Progression after Resection of Non-Invasive Intraductal Papillary Mucinous Neoplasms [published online ahead of print, 2020 Nov 12]. Ann Surg. 2020; https://doi.org/10.1097/SLA.0000000000004488
Rodrigues C, Hank T, Qadan M, et al. Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. Pancreatology. 2020;20(4):722-728. https://doi.org/10.1016/j.pan.2020.03.009
doi: 10.1016/j.pan.2020.03.009 pubmed: 32222340
Psarelli E, Jackson R, et al. Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. JAMA Surg. 2019;154(11):1038–1048. https://doi.org/10.1001/jamasurg.2019.3337
doi: 10.1001/jamasurg.2019.3337 pubmed: 31483448 pmcid: 6727687
Groot VP, Rezaee N, Wu W, et al. Patterns, Timing, and Predictors of Recurrence Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018;267(5):936-945. https://doi.org/10.1097/SLA.0000000000002234
doi: 10.1097/SLA.0000000000002234 pubmed: 28338509
Honselmann KC, Pergolini I, Castillo CF, et al. Timing But Not Patterns of Recurrence Is Different Between Node-negative and Node-positive Resected Pancreatic Cancer. Ann Surg. 2020 Aug;272(2):357-365. https://doi.org/10.1097/sla.0000000000003123 .
doi: 10.1097/sla.0000000000003123 pubmed: 32675550
Habib JR, Kinny-Köster B, Bou-Samra P, et al. Surgical decision making in pancreatic ductal adenocarcinoma: modeling prognosis following pancreatectomy in the era of induction and neoadjuvant chemotherapy. Ann Surg. (Accepted).
Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–99.
doi: 10.3322/caac.21388 pubmed: 28094848
Shimada K, Sakamoto Y, Sano T, Kosuge T, Hiraoka N. Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: a clinicopathologic comparison with a common type of invasive ductal carcinoma. Pancreas. 2006;32(3):281-287. https://doi.org/10.1097/01.mpa.0000202955.33483.e2
doi: 10.1097/01.mpa.0000202955.33483.e2 pubmed: 16628084
Poultsides GA, Reddy S, Cameron JL, et al. Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg. 2010;251(3):470-476. https://doi.org/10.1097/SLA.0b013e3181cf8a19
doi: 10.1097/SLA.0b013e3181cf8a19 pubmed: 20142731
Winter JM, Jiang W, Basturk O, et al. Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (≤20-mm Invasive Component): A Multi-institutional Analysis. Ann Surg. 2016;263(4):793-801. https://doi.org/10.1097/SLA.0000000000001319
doi: 10.1097/SLA.0000000000001319 pubmed: 26135696
Lewis R, Drebin JA, Callery MP, et al. A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma. HPB (Oxford). 2013;15(1):49-60. https://doi.org/10.1111/j.1477-2574.2012.00571.x
doi: 10.1111/j.1477-2574.2012.00571.x pubmed: 23216779
Hayasaki A, Isaji S, Kishiwada M, et al. Survival Analysis in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Chemoradiotherapy Followed by Surgery According to the International Consensus on the 2017 Definition of Borderline Resectable Cancer. Cancers (Basel). 2018;10(3):65. Published 2018 Mar 5. https://doi.org/10.3390/cancers10030065
doi: 10.3390/cancers10030065 pmcid: 5876640
Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011-1024. https://doi.org/10.1016/S0140-6736(16)32409-6
doi: 10.1016/S0140-6736(16)32409-6 pubmed: 28129987
Marchegiani G, Mino-Kenudson M, Ferrone CR, et al. Patterns of Recurrence After Resection of IPMN: Who, When, and How?. Ann Surg. 2015;262(6):1108-1114. https://doi.org/10.1097/SLA.0000000000001008
doi: 10.1097/SLA.0000000000001008 pubmed: 25793719
Chari ST, Yadav D, Smyrk TC, et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology. 2002;123(5):1500-1507. https://doi.org/10.1053/gast.2002.36552
doi: 10.1053/gast.2002.36552 pubmed: 12404225
Hirono S, Shimizu Y, Ohtsuka T, et al. Recurrence patterns after surgical resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas; a multicenter, retrospective study of 1074 IPMN patients by the Japan Pancreas Society. J Gastroenterol. 2020;55(1):86-99. https://doi.org/10.1007/s00535-019-01617-2
doi: 10.1007/s00535-019-01617-2 pubmed: 31463655
Ciprani D, Morales-Oyarvide V, Qadan M, et al. An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN. Pancreatology. 2020;20(4):729-735. https://doi.org/10.1016/j.pan.2020.04.002
doi: 10.1016/j.pan.2020.04.002 pubmed: 32332003
Wasif N, Bentrem DJ, Farrell JJ, et al. Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes. Cancer. 2010;116(14):3369-3377. https://doi.org/10.1002/cncr.25070
doi: 10.1002/cncr.25070 pubmed: 20564064
Chari ST, Yadav D, Smyrk TC, et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology. 2002;123(5):1500-1507. https://doi.org/10.1053/gast.2002.36552
doi: 10.1053/gast.2002.36552 pubmed: 12404225
Maire F, Hammel P, Terris B, et al. Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma. Gut. 2002;51(5):717-722. https://doi.org/10.1136/gut.51.5.717
doi: 10.1136/gut.51.5.717 pubmed: 12377813 pmcid: 1773420
D'Angelica M, Brennan MF, Suriawinata AA, Klimstra D, Conlon KC. Intraductal papillary mucinous neoplasms of the pancreas: an analysis of clinicopathologic features and outcome. Ann Surg. 2004;239(3):400-408. https://doi.org/10.1097/01.sla.0000114132.47816.dd
doi: 10.1097/01.sla.0000114132.47816.dd pubmed: 15075659 pmcid: 1356240
Jang JY, Hwang DW, Kim MA, et al. Analysis of prognostic factors and a proposed new classification for invasive papillary mucinous neoplasms. Ann Surg Oncol. 2011;18(3):644-650. https://doi.org/10.1245/s10434-010-1331-6
doi: 10.1245/s10434-010-1331-6 pubmed: 20924796
Aronsson L, Marinko S, Ansari D, Andersson R. Adjuvant therapy in invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a systematic review. Ann Transl Med. 2019;7(22):689. https://doi.org/10.21037/atm.2019.10.37
doi: 10.21037/atm.2019.10.37 pubmed: 31930090 pmcid: 6944598
Mungo B, Croce C, Oba A, et al. Controversial Role of Adjuvant Therapy in Node-Negative Invasive Intraductal Papillary Mucinous Neoplasm. Ann Surg Oncol. 2021;28(3):1533-1542. https://doi.org/10.1245/s10434-020-08916-6
doi: 10.1245/s10434-020-08916-6 pubmed: 32743713
Worni M, Akushevich I, Gloor B, et al. Adjuvant radiotherapy in the treatment of invasive intraductal papillary mucinous neoplasm of the pancreas: an analysis of the surveillance, epidemiology, and end results registry. Ann Surg Oncol. 2012;19(4):1316-1323. https://doi.org/10.1245/s10434-011-2088-2
doi: 10.1245/s10434-011-2088-2 pubmed: 22002799
Swartz MJ, Hsu CC, Pawlik TM, et al. Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. Int J Radiat Oncol Biol Phys. 2010;76(3):839-844. https://doi.org/10.1016/j.ijrobp.2009.02.071
doi: 10.1016/j.ijrobp.2009.02.071 pubmed: 19647950

Auteurs

Joseph R Habib (JR)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Benedict Kinny-Köster (B)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Neda Amini (N)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Sami Shoucair (S)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

John L Cameron (JL)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Elizabeth D Thompson (ED)

Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Elliot K Fishman (EK)

Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ralph H Hruban (RH)

Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ammar A Javed (AA)

Division of Hepatobiliary and Pancreatic Surgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.

Jin He (J)

Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Christopher L Wolfgang (CL)

Division of Hepatobiliary and Pancreatic Surgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA. Christopher.Wolfgang@nyulangone.org.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH