Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23–24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.
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References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424
Ilic M, Ilic I (2016) Epidemiology of pancreatic cancer. World J Gastroenterol 22(44):9694–9705
Rawla P, Sunkara T, Gaduputi V (2019) Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 10(1):10–27
De La Cruz MS, Young AP, Ruffin MT (2014) Diagnosis and management of pancreatic cancer. Am Fam Phys 89(8):626–632
Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S (2006) Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg 10(4):511–518
Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703
De Ruysscher DPS, Oligometastases DC (2015). In: Peters S (ed) New therapeutic strategies in lung cancers. Springer, Cham
Ghidini M, Petrillo A, Salati M, Khakoo S, Varricchio A, Tomasello G et al (2019) Surgery or locoregional approaches for hepatic oligometastatic pancreatic cancer: myth, hope, or reality? Cancers (Basel). 11:8
Sakaguchi T, Valente R, Tanaka K, Satoi S, Del Chiaro M (2019) Surgical treatment of metastatic pancreatic ductal adenocarcinoma: a review of current literature. Pancreatology 19(5):672–680
Hackert T, Niesen W, Hinz U, Tjaden C, Strobel O, Ulrich A et al (2017) Radical surgery of oligometastatic pancreatic cancer. Eur J Surg Oncol 43(2):358–363
Yasukawa M, Kawaguchi T, Kawai N, Tojo T, Taniguchi S (2017) Surgical treatment for pulmonary metastasis of pancreatic ductal adenocarcinoma: study of 12 cases. Anticancer Res 37(10):5573–5576
Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L et al (2010) Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer 116(24):5608–5618
Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O et al (2009) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol 27(36):6237–6242
Deraco M, Baratti D, Laterza B, Balestra MR, Mingrone E, Macri A et al (2011) Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol 37(1):4–9
Brandl A, Yonemura Y, Glehen O, Sugarbaker PH, Rau B (2020) Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: a multi-institutional cohort from PSOGI. J Clin Oncol 38(4):390
Honoré C, Goéré D, Macovei R, Colace L, Benhaim L, Elias D (2016) Peritoneal carcinomatosis from unusual cancer origins: is there a role for hyperthermic intraperitoneal chemotherapy? J Visc Surg 153(2):101–107
Leigh N, Solomon D, Pletcher E, Labow DM, Magge DR, Sarpel U et al (2020) Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies? World J Surg Oncol 18(1):124
Azzam AZ, Amin TM (2020) Combined Intraoperative Radiotherapy (IORT) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreduction Surgery (CRS) as a Novel Approach in the Management of Resectable Pancreatic Cancer. Gulf J Oncol 1(33):19–26
Tentes AA, Pallas N, Karamveri C, Kyziridis D, Hristakis C (2018) Cytoreduction and HIPEC for peritoneal carcinomatosis of pancreatic cancer. J Buon 23(2):482–487
Schwarz L, Levine EA, Morris D, Spiliotis J, Pocard M, Kianmanesh R et al (2018) CRS with HIPEC for peritoneal carcinomatosis of pancreatic adenocarcinoma. What do we expect? Results of a Multicenter International Study. HPB 20:S324
Farma JM, Pingpank JF, Libutti SK, Bartlett DL, Ohl S, Beresneva T et al (2005) Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion. J Gastrointest Surg 9(9):1346–1353
Tentes AA, Stamou K, Pallas N, Karamveri C, Kyziridis D, Hristakis C (2016) The effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) as an adjuvant in patients with resectable pancreatic cancer. Int J Hypertherm 32(8):895–899
Shiomi H, Naka S, Akabori H, Murakami K, Murata S, Yamamoto H et al (2014) Hyperthermic intraoperative intraperitoneal chemotherapy for advanced pancreatic cancer. HPB 16:610
Satoi S, Fujii T, Yanagimoto H, Motoi F, Kurata M, Takahara N et al (2017) Multicenter phase II study of intravenous and intraperitoneal paclitaxel with S-1 for pancreatic ductal adenocarcinoma patients with peritoneal metastasis. Ann Surg 265(2):397–401
Yonemura Y, Canbay E, Li Y, Coccolini F, Glehen O, Sugarbaker PH et al (2016) A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent. Eur J Surg Oncol 42(8):1123–1131
Sugarbaker PH (1989) Surgical treatment of peritoneal carcinomatosis: 1988 Du Pont lecture. Can J Surg 32(3):164–170
Chua TC, Morris DL, Esquivel J (2010) Impact of the peritoneal surface disease severity score on survival in patients with colorectal cancer peritoneal carcinomatosis undergoing complete cytoreduction and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 17(5):1330–1336
Winer J, Zenati M, Ramalingam L, Jones H, Zureikat A, Holtzman M et al (2014) Impact of aggressive histology and location of primary tumor on the efficacy of surgical therapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 21(5):1456–1462
Yonemura Y, Canbay E, Ishibashi H (2013) Prognostic factors of peritoneal metastases from colorectal cancer following cytoreductive surgery and perioperative chemotherapy. Sci World J 2013:978394
Auer RC, Sivajohanathan D, Biagi J, Conner J, Kennedy E, May T (2020) Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review. Eur J Cancer 127:76–95
Goéré D, Passot G, Gelli M, Levine EA, Bartlett DL, Sugarbaker PH et al (2017) Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI). Int J Hyperth 33(5):520–527
Thomassen I, Lemmens VE, Nienhuijs SW, Luyer MD, Klaver YL, de Hingh IH (2013) Incidence, prognosis, and possible treatment strategies of peritoneal carcinomatosis of pancreatic origin: a population-based study. Pancreas 42(1):72–75
Takahara N, Isayama H, Nakai Y, Sasaki T, Saito K, Hamada T et al (2015) Pancreatic cancer with malignant ascites: clinical features and outcomes. Pancreas 44(3):380–385
Jo JH, Chung MJ, Park JY, Bang S, Park SW, Chung JB et al (2014) Clinical characteristics of long-term survivors of inoperable pancreatic cancer: an 8-year cohort analysis in Korea. Pancreas 43(7):1022–1031
Clark CJ, Traverso LW (2010) Positive peritoneal lavage cytology is a predictor of worse survival in locally advanced pancreatic cancer. Am J Surg 199(5):657–662
Esquivel J, Sticca R, Sugarbaker P, Levine E, Yan TD, Alexander R et al (2007) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement Society of Surgical Oncology. Ann Surg Oncol 14(1):128–133
Tewari M, Hazrah P, Kumar V, Shukla HS (2010) Options of restorative pancreaticoenteric anastomosis following pancreaticoduodenectomy: a review. Surg Oncol 19(1):17–26
Dubé P, Sideris L, Law C, Mack L, Haase E, Giacomantonio C et al (2015) Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms. Curr Oncol 22(2):e100–e112
Downs-Canner S, Ding Y, Magge DR, Jones H, Ramalingam L, Zureikat A et al (2015) A comparative analysis of postoperative pancreatic fistulas after surgery with and without hyperthermic intraperitoneal chemoperfusion. Ann Surg Oncol 22(5):1651–1657
Doud AN, Randle RW, Clark CJ, Levine EA, Swett KR, Shen P et al (2015) Impact of distal pancreatectomy on outcomes of peritoneal surface disease treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 22(5):1645–1650
Schwarz L, Votanopoulos K, Morris D, Yonemura Y, Deraco M, Piso P et al (2016) Is the combination of distal pancreatectomy and cytoreductive surgery with HIPEC reasonable? Results of an international multicenter study. Ann Surg 263(2):369–375
Mizrahi JD, Surana R, Valle JW, Shroff RT (2020) Pancreatic cancer. Lancet 395(10242):2008–2020
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297(3):267–277
Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D et al (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304(10):1073–1081
Goéré D, Glehen O, Quenet F, Guilloit JM, Bereder JM, Lorimier G et al (2020) Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncol 21(9):1147–1154
Klaver CEL, Wisselink DD, Punt CJA, Snaebjornsson P, Crezee J, Aalbers AGJ et al (2019) Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol 4(10):761–770
Sugarbaker PH (2017) Strategies to improve local control of resected pancreas adenocarcinoma. Surg Oncol 26(1):63–70
Ridwelski K, Meyer F, Hribaschek A, Kasper U, Lippert H (2002) Intraoperative and early postoperative chemotherapy into the abdominal cavity using gemcitabine may prevent postoperative occurence of peritoneal carcinomatosis. J Surg Oncol 79(1):10–16
Kamath A, Yoo D, Stuart OA, Bijelic L, Sugarbaker PH (2009) Rationale for an intraperitoneal gemcitabine chemotherapy treatment for patients with resected pancreatic cancer. Recent Pat Anticancer Drug Discov 4(2):174–179
García Santos EP, Padilla Valverde D, Villarejo Campos P, Sánchez García S, Martín Fernández J (2018) HIPEC with gemcitabine as an adjuvant locoregional treatment after radical surgery in pancreatic cancer. Presentation of the clinical trial N-2016-004298-41. Pleura and Peritoneum. 3:sA206.
The Chicago Consensus on Peritoneal Surface Malignancies (2020) Management of Gastric Metastases. Ann Surg Oncol 27(6):1768–1773
Manzanedo I, Pereira F, Rihuete Caro C, Pérez-Viejo E, Serrano Á, Gutiérrez Calvo A et al (2019) Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer with Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP). Ann Surg Oncol 26(8):2615–2621
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AB and PK had the idea for the article; AB and MW performed the literature search and data analysis; AB, MW and MP drafted the manuscript and all authors critically revised the work. PK is guarantor for the project.
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Brind’Amour, A., Webb, M., Parapini, M. et al. The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review. Clin Exp Metastasis 38, 187–196 (2021). https://doi.org/10.1007/s10585-021-10074-2
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DOI: https://doi.org/10.1007/s10585-021-10074-2