{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:20:34Z","timestamp":1793215234202,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and \u2018other events\u2019, i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LNhigh (ypN3 lymph node stage or a lymph node ratio &gt;20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LNhigh was an independent risk factor for \u2018other events\u2019. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LNhigh were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies.<\/jats:p>","DOI":"10.3390\/cancers13184626","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:00:44Z","timestamp":1631707244000},"page":"4626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2073-4485","authenticated-orcid":false,"given":"Irene A.","family":"Caspers","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"},{"name":"Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Sikorska","sequence":"additional","affiliation":[{"name":"Department of Biometrics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-0180","authenticated-orcid":false,"given":"Astrid E.","family":"Slagter","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy M.","family":"van Amelsfoort","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-2221","authenticated-orcid":false,"given":"Elma","family":"Meershoek-Klein Kranenbarg","sequence":"additional","affiliation":[{"name":"Department of Biometrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis J. H.","family":"van de Velde","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pehr","family":"Lind","sequence":"additional","affiliation":[{"name":"Department of Oncology, Stockholm S\u00f6der Hospital, 118 83 Stockholm, Sweden"},{"name":"Department of Oncology and Pathology, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-1273","authenticated-orcid":false,"given":"Marianne","family":"Nordsmark","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin P. M.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"},{"name":"Department of Radiation Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna W.","family":"van Sandick","sequence":"additional","affiliation":[{"name":"Department of Surgery, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Cats","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-0760","authenticated-orcid":false,"given":"Nicole C. T.","family":"van Grieken","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/S0140-6736(18)32557-1","article-title":"Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2\/3 trial","volume":"393","author":"Homann","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa055531","article-title":"Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer","volume":"355","author":"Cunningham","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Seyfried, F., von Rahden, B.H., Miras, A.D., Gasser, M., Maeder, U., Kunzmann, V., Germer, C.-T., Pelz, J.O., and Kerscher, A.G. (2015). Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin\u2013a longitudinal experience from a prospectively collected database of 1108 patients. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1081-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.jamcollsurg.2014.03.062","article-title":"Rates and patterns of recurrence after curative intent resection for gastric cancer: A United States multi-institutional analysis","volume":"219","author":"Spolverato","year":"2014","journal-title":"J. Am. Coll. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejso.2012.12.013","article-title":"Risk factors of peritoneal recurrence in eso-gastric signet ring cell adenocarcinoma: Results of a multicentre retrospective study","volume":"39","author":"Messager","year":"2013","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s10120-019-00956-6","article-title":"Recurrence after preoperative chemotherapy and surgery for gastric adenocarcinoma: A multicenter study","volume":"22","author":"Mokadem","year":"2019","journal-title":"Gastric Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/s10120-021-01160-1","article-title":"Synchronous peritoneal metastases of gastric cancer origin: Incidence, treatment and survival of a nationwide Dutch cohort","volume":"24","author":"Koemans","year":"2021","journal-title":"Gastric Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Koemans, W., Luijten, J., van der Kaaij, R., Grootscholten, C., Snaebjornsson, P., Verhoeven, R., and van Sandick, J. (2020). The metastatic pattern of intestinal and diffuse type gastric carcinoma\u2013A Dutch national cohort study. Cancer Epidemiol., 69.","DOI":"10.1016\/j.canep.2020.101846"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3109\/0284186X.2013.850740","article-title":"Chemotherapy as palliative treatment for peritoneal carcinomatosis of gastric origin","volume":"53","author":"Thomassen","year":"2014","journal-title":"Acta Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/jso.26366","article-title":"Tumor characteristics and clinical outcome of peritoneal metastasis of gastric origin treated with a hyperthermic intraperitoneal chemotherapy procedure in the PERISCOPE I trial","volume":"123","author":"Koemans","year":"2021","journal-title":"J. Surg. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10120-019-00978-0","article-title":"Peritoneal metastasis in gastric cancer: Results from the German database","volume":"23","author":"Rau","year":"2020","journal-title":"Gastric Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.ejso.2018.06.036","article-title":"Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis","volume":"44","author":"Caro","year":"2018","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Marano, L., Marrelli, D., Sammartino, P., Biacchi, D., Graziosi, L., Marino, E., Coccolini, F., Fugazzola, P., Valle, M., and Federici, O. (2021). Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of \u2018Italian Peritoneal Surface Malignancies Oncoteam\u2014SICO\u2019. Ann. Surg. Oncol., 1\u201311.","DOI":"10.1245\/s10434-021-10157-0"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Koemans, W., Van Der Kaaij, R., Boot, H., Buffart, T., Veenhof, A., Hartemink, K., Grootscholten, C., Snaebjornsson, P., Retel, V., and van Tinteren, H. (2019). Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II). BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5640-2"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brenkman, H., P\u00e4eva, M., Van Hillegersberg, R., Ruurda, J., and Haj Mohammad, N. (2019). Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer\u2014A Systematic Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101685"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Glehen, O., Passot, G., Villeneuve, L., Vaudoyer, D., Bin-Dorel, S., Boschetti, G., Piaton, E., and Garofalo, A. (2014). GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: A randomized and multicenter phase III study. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-183"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1002\/bjs.11588","article-title":"Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results","volume":"107","author":"Kaaij","year":"2020","journal-title":"J. Br. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/jso.24405","article-title":"Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration","volume":"114","author":"Chang","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1245\/s10434-019-07624-0","article-title":"Gastric cancer peritoneal carcinomatosis risk score","volume":"27","author":"Ji","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Riihim\u00e4ki, M., Hemminki, A., Sundquist, K., Sundquist, J., and Hemminki, K. (2016). Metastatic spread in patients with gastric cancer. Oncotarget, 7.","DOI":"10.18632\/oncotarget.10740"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/ijc.28373","article-title":"Peritoneal carcinomatosis of gastric origin: A population-based study on incidence, survival and risk factors","volume":"134","author":"Thomassen","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dikken, J.L., van Sandick, J.W., Swellengrebel, H.M., Lind, P.A., Putter, H., Jansen, E.P., Boot, H., van Grieken, N.C., van de Velde, C.J., and Verheij, M. (2011). Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-329"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/S1470-2045(18)30132-3","article-title":"Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): An international, open-label, randomised phase 3 trial","volume":"19","author":"Cats","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.ejso.2018.02.004","article-title":"Surgical morbidity and mortality after neoadjuvant chemotherapy in the CRITICS gastric cancer trial","volume":"44","author":"Claassen","year":"2018","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma: An attempt at a histo-clinical classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_27","unstructured":"Amin, M.B., Edge, S.B., and Greene, F.L. (2017). AJCC Cancer Staging Manual, Springer. [8th ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.annonc.2020.11.004","article-title":"Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial","volume":"32","author":"Hartgrink","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_29","first-page":"710","article-title":"Microscopic peritoneal carcinomatosis in gastric cancer: Prevalence, prognosis and predictive factors","volume":"15","author":"Pasqual","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Chang, K.K., Yoon, C., Tang, L.H., Strong, V.E., and Yoon, S.S. (2018). Lauren histologic type is the most important factor associated with pattern of recurrence following resection of gastric adenocarcinoma. Ann. Surg., 267.","DOI":"10.1097\/SLA.0000000000002040"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10120-018-0875-1","article-title":"Impact of upfront randomization for postoperative treatment on quality of surgery in the CRITICS gastric cancer trial","volume":"22","author":"Claassen","year":"2019","journal-title":"Gastric Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Slagter, A.E., Jansen, E.P.M., van Laarhoven, H.W.M., van Sandick, J.W., van Grieken, N.C.T., Sikorska, K., Cats, A., Muller-Timmermans, P., Hulshof, M., and Boot, H. (2018). CRITICS-II: A multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4770-2"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Leong, T., Smithers, B.M., Michael, M., Gebski, V., Boussioutas, A., Miller, D., Simes, J., Zalcberg, J., Haustermans, K., and Lordick, F. (2015). TOPGEAR: A randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG\/TROG\/EORTC\/NCIC CTG). BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1529-x"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Coccolini, F., Celotti, A., Ceresoli, M., Montori, G., Marini, M., Catena, F., and Ansaloni, L. (2016). Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer\u2014effects on overall and disease free survival. J. Gastrointest. Oncol., 7.","DOI":"10.21037\/jgo.2016.06.05"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S2468-1253(19)30239-0","article-title":"Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): A multicentre, open-label, randomised trial","volume":"4","author":"Klaver","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kwon, S.J. (2011). Evaluation of the 7th UICC TNM staging system of gastric cancer. J. Gastric Cancer, 11.","DOI":"10.5230\/jgc.2011.11.2.78"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/18\/4626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:13Z","timestamp":1760166013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/18\/4626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":36,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cancers13184626"],"URL":"https:\/\/doi.org\/10.3390\/cancers13184626","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]}}}