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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2019

Open Access 01-07-2019 | Metastasis | Gastrointestinal Oncology

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study

Authors: Judith E. K. R. Hentzen, MD, Koen P. Rovers, MD, Hendrien Kuipers, BSc, Willemijn Y. van der Plas, BSc, Lukas B. Been, MD, PhD, Frederik J. H. Hoogwater, MD, PhD, Robert J. van Ginkel, MD, PhD, Patrick H. J. Hemmer, MD, Gooitzen M. van Dam, MD, PhD, Ignace H. J. T. de Hingh, MD, PhD, Schelto Kruijff, MD, PhD

Published in: Annals of Surgical Oncology | Issue 7/2019

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Abstract

Background

Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC.

Methods

Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien–Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan–Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis.

Results

The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18–2.26).

Conclusions

Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.
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Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods, and major patterns in GLOBACAN 2012. Int J Cancer. 2015;136:359–86.CrossRef
2.
Chu DZ, Lang NP, Thompson C, Osteen PK, Westbrook KC. Peritoneal carcinomatosis in nongynecologic malignancy: a prospective study of prognostic factors. Cancer. 1989;63:364–7.CrossRefPubMed
3.
Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88:358–63.CrossRefPubMed
4.
Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89:1545–50.CrossRefPubMed
5.
Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128:2717–25.CrossRefPubMed
6.
Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence, and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012;99:699–705.CrossRefPubMed
7.
Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg. 2006;243:212–22.CrossRefPubMedPubMedCentral
8.
Razenberg LG, Lemmens VE, Verwaal VJ, Punt CJ, Tanis PJ, Creemers GJ, de Hingh IH. Challenging the dogma of colorectal peritoneal metastases as an untreatable condition: results of a population-based study. Eur J Cancer. 2016;65:113–20.CrossRefPubMed
9.
Razenberg LG, van Gestel YR, Lemmens VE, de Hingh IH, Creemers GJ. Bevacizumab in addition to palliative chemotherapy in patients with peritoneal carcinomatosis of colorectal origin: a nationwide population-based study. Clin Colorectal Cancer. 2016;15:41–6.CrossRef
10.
Pelz JO, Chua TC, Esquivel J, et al. Evaluation of best supportive care and systemic chemotherapy as treatment stratified according to the retrospective peritoneal surface disease severity score (PSDSS) for peritoneal carcinomatosis of colorectal origin. BMC Cancer. 2010;10:689.CrossRefPubMedPubMedCentral
11.
Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-Year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15:2426–32.CrossRefPubMed
12.
Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–5.CrossRefPubMed
13.
Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ III. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.CrossRefPubMed
14.
Van Oudheusden TR, Nienhuijs SW, Luyer MD, Nieuwenhuijzen GA, Lemmens VE, Rutten HJ, de Hingh IH. Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: a systematic review. Eur J Surg Oncol. 2015;41:1269–77.CrossRefPubMed
15.
Baratti D, Kusamura S, Pietrantonio F, Guaglio M, Niger M, Deraco M. Progress in treatments for colorectal cancer peritoneal metastases during the years 2010–2015: a systemic review. Crit Rev Oncol Hematol. 2016;100:209–22.CrossRefPubMed
16.
Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systemic review of morbidity and mortality. Ann Surg. 2009;249:900–7.CrossRefPubMed
17.
Kuijpers AM, Mirck B, Aalbers AG, et al. Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol. Ann Surg Oncol. 2013;20:4224–30.CrossRefPubMedPubMedCentral
18.
Frøysnes IS, Larsen SG, Spasojevic M, Dueland S, Flatmark K. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis in Norway: prognostic factors and oncologic outcome in an national patient cohort. J Surg Oncol. 2016;114:222–7.CrossRefPubMed
19.
Braam HJ, van Oudheusden TR, de Hingh IH, Nienhuijs SW, Boerma D, Wietzer MJ, van Ramshorst B. Patterns of recurrence following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. J Surg Oncol. 2014;109:841–7.CrossRefPubMed
20.
Teo MC, Ching Tan GH, Lim C, Chia CS, Tham CK, Soo KC. Colorectal peritoneal carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: the experience of a tertiary Asian Center. Asian J Surg. 2015;38:65–73.CrossRefPubMed
21.
Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–8.CrossRefPubMed
22.
Kwakman R, Schrama AM, van Olmen JP, et al. Clinocpathological parameters in patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer metastases: a meta-analysis. Ann Surg. 2016;263:1102–11.CrossRefPubMed
23.
Cashin PH, Dranichnikov F, Mahteme H. Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy treatment of colorectal peritoneal metastases: cohort analysis of high-volume disease and cure rate. J Surg Oncol. 2014;110:203–6.CrossRefPubMed
24.
Sugarbaker PH. Cytoreductive surgery plus hyperthermic perioperative chemotherapy for selected patients with peritoneal metastases from colorectal cancer: a new standard of care or an experimental approach? Gastroenterol Res Pract. 2012;2012:309417.PubMedPubMedCentral
25.
Yonemura Y, Elnemr A, Endou Y, Ishibashi H, Mizumoto A, Miura M, Li Y. Surgical results of patients with peritoneal carcinomatosis treated with cytoreductive surgery using a new technique named aqua dissection. Gastroenterol Res Pract. 2012;2012:521487.PubMedPubMedCentral
26.
Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92.CrossRefPubMed
27.
Verwaal VJ, van Ruth S, Witkamp A, Boot H, van Slooten G, Zoetmulder FA. Long-term survival of peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2005;12:65–71.CrossRefPubMed
28.
Sugarbaker PH, Averbach AM, Jacquet P, Stuart OA, Stephens AD. Hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) with mitomycin C. Surg Technol Int. 1996;5:245–9.PubMed
29.
Sugarbaker PH. Technical handbook for the integration of cytoreductive surgery and perioperative intraperitoneal chemotherapy into the surgical management of gastrointestinal and gynecologic malignancy. 4th ed. Ludann Company, Grand Rapids, MI, 2005.
30.
Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.CrossRefPubMed
31.
Elias D, Faron M, Iuga BS, et al. Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers. Ann Surg. 2015;261:157–63.CrossRefPubMed
32.
Hompes D, D’Hoore A, van Cutsem E, et al. The treatment of peritoneal carcinomatosis of colorectal cancer with complete cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) with oxaliplatin: a Belgian multicentre prospective phase II clinical study. Ann Surg. 2012;19:2186–94.CrossRef
33.
Rovers KP, Simkens GA, Punt CJ, van Dieren S, Tanis PJ, de Hingh IH. Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review. Crit Rev Oncol Hematol. 2017;114:53–62.CrossRefPubMed
34.
Chia CS, Tan GH, Lim C, Soo KC, Teo MC. Prospective quality of life study for colorectal cancer patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2016;23:2905–13.CrossRefPubMed
35.
McQuellon RP, Loggie BW, Fleming RA, Russell GB, Lehman AB, Rambo TD. Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal carcinomatosis. Eur J Surg Oncol. 2001;27:65–73.CrossRefPubMed
36.
McQuellon RP, Danhauer SC, Russell GB, Shen P, Fenstermaker J, Stewart JH, Levine EA. Monitoring health outcomes following cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. Ann Surg Oncol. 2007;14:1105–13.CrossRefPubMed
37.
McQuellon RP, Loggie BW, Lehman AB, Russell GB, Fleming RA, Shen P, Levine EA. Long-term survivorship and quality of life after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. Ann Surg Oncol. 2003;10:155–62.CrossRefPubMed
38.
Schmidt U, Dahlke MH, Klempnauer J, Schlitt HJ, Piso P. Perioperative morbidity and quality of life in long-term survivors following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol. 2005;31:53–8.CrossRefPubMed
39.
Tuttle TM, Zhang Y, Greeno E, Knutsen A. Toxicity and quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2006;13:1627–32.CrossRefPubMed
40.
Hill AR, McQuellon RP, Russell GB, Shen P, Stewart JH IV, Levine EA. Survival and quality of life following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis of colonic origin. Ann Surg Oncol. 2011;18:3673–9.CrossRefPubMedPubMedCentral
41.
Hinkle NM, Botta V, Sharpe JP, Dickson P, Deneve J, Munene G. The impact of early recurrence on quality of life after cytoreduction and HIPEC. Am Surg. 2017;83:633–9.PubMed
42.
Simkens GA, van Oudheusden TR, Luyer MD,Nienhuijs SW, Nieuwenhuijzen GA, Rutten HJ, de Hingh IH. Serious postoperative complications affect early recurrence after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis. Ann Surg Oncol. 2015;22:2656–62.CrossRefPubMed
43.
Goere D, Malka D, Tzanis D, et al. Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg. 2013;257:1065–71.CrossRefPubMed
44.
Koningsrainer I, Horvath P, Struller F, Forkl V, Koningsrainer A, Beckert S. Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies. Langenbecks Arch Surg. 2013;398:745–9.CrossRef
45.
Baratti D, Kusamura S, Iusco D, et al. Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: a two-center study of 101 patients. Dis Colon Rectum. 2014;57:858–68.CrossRefPubMed
46.
De Sousa E Melo F, Wang X, Jansen M, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med. 2013;19:614–8.CrossRef
47.
Sadanandam A, Lyssiotis CA, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med. 2013;19:619–25.CrossRefPubMedPubMedCentral
48.
Sadanandam A, Wang X, de Sousa E Melo F, Gray JW, Vermeulen L, Hanahan D, Medema JP. Reconciliation of classification systems defining molecular subtypes of colorectal cancer: interrelationships and clinical implications. Cell Cycle. 2014;13:353–7.
49.
Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med. 2013;10:e1001453.CrossRefPubMedPubMedCentral
50.
van Dam GM, Themelis G, Crane LM, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med. 2011;17:1315–9.CrossRefPubMed
51.
Tummers QR, Hoogstins CE, Gaarenstroom KN, et al. Intraoperative imaging of folate receptor alpha-positive ovarian and breast cancer using the tumor-specific agent EC17. Oncotarget. 2016;7:32144–55.CrossRefPubMedPubMedCentral
52.
de Boer E, Warram JM, Tucker MD, et al. In vivo fluorescence immunohistochemistry: localization of fluorescently labeled cetuximab in squamous cell carcinomas. Sci Rep. 2015;5:10169.CrossRefPubMedPubMedCentral
53.
Boogerd LSF, Hoogstins CES, Schaap DP, et al. Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study. Lancet Gastroenterol Hepatol. 2018;3:181–91.CrossRefPubMed
54.
Harlaar NJ, Koller M, de Jongh SJ, et al. Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study. Lancet Gastroenterol Hepatol. 2016;1:283–90.CrossRefPubMed
Metadata
Title
Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study
Authors
Judith E. K. R. Hentzen, MD
Koen P. Rovers, MD
Hendrien Kuipers, BSc
Willemijn Y. van der Plas, BSc
Lukas B. Been, MD, PhD
Frederik J. H. Hoogwater, MD, PhD
Robert J. van Ginkel, MD, PhD
Patrick H. J. Hemmer, MD
Gooitzen M. van Dam, MD, PhD
Ignace H. J. T. de Hingh, MD, PhD
Schelto Kruijff, MD, PhD
Publication date
01-07-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07294-y

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