{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:05:23Z","timestamp":1769421923034,"version":"3.49.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["surg case rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Management of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept\u2009+\u2009FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>The patient was a 37\u00a0year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab\u2009+\u2009FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab\u2009+\u2009FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept\u2009+\u2009FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2\u00a0years during aflibercept\u2009+\u2009FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2\u00a0years and 3\u00a0months after the last operation (6\u00a0years since initiation of treatment), without additional chemotherapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept\u2009+\u2009FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab. <\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40792-024-02033-2","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:01:51Z","timestamp":1728360111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RAS mutant transverse colon cancer with multiple liver metastases achieving long-term disease-free survival with postoperative maintenance therapy with aflibercept\u2009+\u2009FOLFIRI and four repeated radical resections: a case report"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1895-9226","authenticated-orcid":false,"given":"Yasushi","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Otake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiro","family":"Ryujin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuho","family":"Ebata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Harima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Natsugoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Yoshiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuro","family":"Kawazoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensuke","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Zaitsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Hisamatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Ando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Oki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoharu","family":"Yoshizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"2033_CR1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.4240\/wjgs.v13.i8.756","volume":"13","author":"Y Kitano","year":"2021","unstructured":"Kitano Y, Hayashi H, Matsumoto T, Kinoshita S, Sato H, Shiraishi Y, et al. Borderline resectable for colorectal liver metastases: present status and future perspective. World J Gastrointest Surg. 2021;13:756\u201363.","journal-title":"World J Gastrointest Surg"},{"key":"2033_CR2","doi-asserted-by":"publisher","first-page":"8198","DOI":"10.1245\/s10434-021-10220-w","volume":"28","author":"F Giuliante","year":"2021","unstructured":"Giuliante F, Vigan\u00f2 L, De Rose AM, Mirza DF, Lapointe R, Kaiser G, et al. Liver-first approach for synchronous colorectal metastases: analysis of 7360 patients from the livermetsurvey registry. Ann Surg Oncol. 2021;28:8198\u2013208.","journal-title":"Ann Surg Oncol"},{"key":"2033_CR3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s41416-023-02496-4","volume":"130","author":"H-J Schmoll","year":"2023","unstructured":"Schmoll H-J, Mann J, Meinert F, Garlipp B, Borchert K, Vogel A, et al. Efficacy and quality of life for FOLFOX\/bevacizumab +\/\u2212 irinotecan in first-line metastatic colorectal cancer\u2014final results of the AIO CHARTA trial. Br J Cancer. 2023;130:233\u201341.","journal-title":"Br J Cancer"},{"key":"2033_CR4","doi-asserted-by":"publisher","first-page":"171","DOI":"10.21037\/atm-21-6731","volume":"10","author":"C Shen","year":"2022","unstructured":"Shen C, Hu H, Cai Y, Ling J, Zhang J, Wu Z, et al. mFOLFOXIRI with or without bevacizumab for conversion therapy of RAS\/BRAF\/PIK3CA mutant unresectable colorectal liver metastases: the FORBES non-randomized phase II trial. Ann Transl Med. 2022;10:171.","journal-title":"Ann Transl Med"},{"key":"2033_CR5","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.3892\/ol.2016.5068","volume":"12","author":"J Alcaide","year":"2016","unstructured":"Alcaide J, Delgado M, Leger\u00e9n M, Jurado JM, Blancas I, Pereda T, et al. Efficacy and safety of aflibercept in metastatic colorectal cancer pretreated with bevacizumab: a report of five cases. Oncol Lett. 2016;12:3127\u201334.","journal-title":"Oncol Lett"},{"key":"2033_CR6","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/S1470-2045(15)70127-0","volume":"16","author":"J Tabernero","year":"2015","unstructured":"Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16:499\u2013508.","journal-title":"Lancet Oncol"},{"key":"2033_CR7","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s11523-016-0447-4","volume":"11","author":"M Scartozzi","year":"2016","unstructured":"Scartozzi M, Vincent L, Chiron M, Cascinu S. Aflibercept, a new way to target angiogenesis in the second line treatment of metastatic colorectal cancer (mCRC). Target Oncol. 2016;11:489\u2013500.","journal-title":"Target Oncol"},{"key":"2033_CR8","doi-asserted-by":"publisher","first-page":"109","DOI":"10.4240\/wjgs.v2.i4.109","volume":"2","author":"G Kir","year":"2010","unstructured":"Kir G, Gurbuz A, Karateke A, Kir M. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma. World J Gastrointest Surg. 2010;2:109\u201316.","journal-title":"World J Gastrointest Surg"},{"key":"2033_CR9","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","volume":"27","author":"E Van Cutsem","year":"2016","unstructured":"Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386\u2013422.","journal-title":"Ann Oncol"},{"key":"2033_CR10","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00595-021-02403-5","volume":"52","author":"M Sugiyama","year":"2022","unstructured":"Sugiyama M, Uehara H, Shin Y, Shiokawa K, Fujimoto Y, Mano Y, et al. Indications for conversion hepatectomy for initially unresectable colorectal cancer with liver metastasis. Surg Today. 2022;52:633\u201342.","journal-title":"Surg Today"},{"key":"2033_CR11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01225","author":"C Cremolini","year":"2020","unstructured":"Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, et al. Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus bevacizumab as initial therapy of unresectable metastatic colorectal cancer. J Clin Oncol. 2020. https:\/\/doi.org\/10.1200\/JCO.20.01225.","journal-title":"J Clin Oncol"},{"key":"2033_CR12","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12957-017-1123-6","volume":"15","author":"M D\u2019Hondt","year":"2017","unstructured":"D\u2019Hondt M, Lucidi V, Vermeiren K, Van Den Bossche B, Donckier V, Sergeant G. The interval approach: an adaptation of the liver-first approach to treat synchronous liver metastases from rectal cancer. World J Surg Oncol. 2017;15:54.","journal-title":"World J Surg Oncol"},{"key":"2033_CR13","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/hpb.12083","volume":"16","author":"VWT Lam","year":"2014","unstructured":"Lam VWT, Laurence JM, Pang T, Johnston E, Hollands MJ, Pleass HCC, et al. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. HPB. 2014;16:101\u20138.","journal-title":"HPB"},{"key":"2033_CR14","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s10147-022-02259-w","volume":"28","author":"J Watanabe","year":"2023","unstructured":"Watanabe J, Terazawa T, Yamane S, Kazama H, Uetake H, Yoshino T. Aflibercept with FOLFIRI in Japanese patients with metastatic colorectal cancer: results of a post-marketing surveillance. Int J Clin Oncol. 2023;28:130\u20138.","journal-title":"Int J Clin Oncol"},{"key":"2033_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040844","author":"K Muro","year":"2020","unstructured":"Muro K, Salinardi T, Singh AR, Macarulla T. Safety of Aflibercept in metastatic colorectal cancer: a literature review and expert perspective on clinical and real-world data. Cancers. 2020. https:\/\/doi.org\/10.3390\/cancers12040844.","journal-title":"Cancers"},{"key":"2033_CR16","doi-asserted-by":"publisher","first-page":"3499","DOI":"10.1200\/JCO.2012.42.8201","volume":"30","author":"E Van Cutsem","year":"2012","unstructured":"Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausov\u00e1 J, Macarulla T, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499\u2013506.","journal-title":"J Clin Oncol"},{"key":"2033_CR17","doi-asserted-by":"publisher","first-page":"766","DOI":"10.3389\/fonc.2019.00766","volume":"9","author":"A Ottaiano","year":"2019","unstructured":"Ottaiano A, Capozzi M, Tafuto S, De Stefano A, De Divitiis C, Romano C, et al. Folfiri-aflibercept vs. folfiri-bevacizumab as second line treatment of RAS mutated metastatic colorectal cancer in real practice. Front Oncol. 2019;9:766.","journal-title":"Front Oncol"},{"key":"2033_CR18","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1002\/cam4.1903","volume":"8","author":"A Fern\u00e1ndez Montes","year":"2019","unstructured":"Fern\u00e1ndez Montes A, Mart\u00ednez Lago N, Covela R\u00faa M, de la C\u00e1mara GJ, Gonz\u00e1lez Villaroel P, M\u00e9ndez M\u00e9ndez JC, et al. Efficacy and safety of FOLFIRI\/aflibercept in second-line treatment of metastatic colorectal cancer in a real-world population: Prognostic and predictive markers. Cancer Med. 2019;8:882\u20139.","journal-title":"Cancer Med"},{"key":"2033_CR19","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1158\/1078-0432.CCR-19-1985","volume":"26","author":"E Van Cutsem","year":"2020","unstructured":"Van Cutsem E, Paccard C, Chiron M, Tabernero J. Impact of prior bevacizumab treatment on VEGF-A and PlGF levels and outcome following second-line aflibercept treatment: biomarker post hoc analysis of the VELOUR trial. Clin Cancer Res. 2020;26:717\u201325.","journal-title":"Clin Cancer Res"},{"key":"2033_CR20","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00268-017-4265-3","volume":"42","author":"J Bellier","year":"2018","unstructured":"Bellier J, De Wolf J, Hebbar M, Amrani ME, Desauw C, Leteurtre E, et al. Repeated resections of hepatic and pulmonary metastases from colorectal cancer provide long-term survival. World J Surg. 2018;42:1171\u20139.","journal-title":"World J Surg"},{"key":"2033_CR21","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s40792-020-00913-x","volume":"6","author":"K Matsuishi","year":"2020","unstructured":"Matsuishi K, Miyamoto Y, Hiyoshi Y, Tokunaga R, Imai K, Hayashi H, et al. Ongoing 5\u00a0year+ survival after multiple metastasectomies, followed by CAPOX plus bevacizumab, for metastatic colorectal cancer. Surg Case Rep. 2020;6:149.","journal-title":"Surg Case Rep"},{"key":"2033_CR22","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.ijsu.2017.11.032","volume":"48","author":"D Heise","year":"2017","unstructured":"Heise D, Bayings W, Tuinhof A, Eickhoff R, Kroh A, Ulmer F, et al. Long-term outcome and quality of life after initial and repeat resection of colorectal liver metastasis: a retrospective analysis. Int J Surg. 2017;48:281\u20135.","journal-title":"Int J Surg"},{"key":"2033_CR23","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1007\/s00384-013-1670-4","volume":"28","author":"HP Neeff","year":"2013","unstructured":"Neeff HP, Drognitz O, Holzner P, Klock A, Bronsert P, Hopt UT, et al. Outcome after repeat resection of liver metastases from colorectal cancer. Int J Colorectal Dis. 2013;28:1135\u201341.","journal-title":"Int J Colorectal Dis"},{"key":"2033_CR24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/jso.20803","volume":"96","author":"F Erroi","year":"2007","unstructured":"Erroi F, Scarpa M, Angriman I, Cecchetto A, Pasetto L, Mollica E, et al. Ovarian metastasis from colorectal cancer: prognostic value of radical oophorectomy. J Surg Oncol. 2007;96:113\u20137.","journal-title":"J Surg Oncol"},{"key":"2033_CR25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.athoracsur.2016.08.084","volume":"103","author":"T Hishida","year":"2017","unstructured":"Hishida T, Tsuboi M, Okumura T, Boku N, Ohde Y, Sakao Y, et al. Does repeated lung resection provide long-term survival for recurrent pulmonary metastases of colorectal cancer? results of a retrospective japanese multicenter study. Ann Thorac Surg. 2017;103:399\u2013405.","journal-title":"Ann Thorac Surg"},{"key":"2033_CR26","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1007\/s00595-013-0735-x","volume":"44","author":"H Ozawa","year":"2014","unstructured":"Ozawa H, Kotake K, Kobayashi H, Kobayashi H, Sugihara K. Prognostic factors for peritoneal carcinomatosis originating from colorectal cancer: an analysis of 921 patients from a multi-institutional database. Surg Today. 2014;44:1643\u201350.","journal-title":"Surg Today"},{"key":"2033_CR27","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1002\/cam4.5195","volume":"12","author":"K Bang","year":"2023","unstructured":"Bang K, Kim JE, Kim TW, Kim SY, Lim S-B, Park IJ, et al. Clinical outcomes of curative surgical resection of peritoneal metastasis in patients with colorectal cancer: a long-term follow-up study. Cancer Med. 2023;12:2861\u20138.","journal-title":"Cancer Med"}],"container-title":["Surgical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40792-024-02033-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40792-024-02033-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40792-024-02033-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:05:16Z","timestamp":1728360316000},"score":1,"resource":{"primary":{"URL":"https:\/\/surgicalcasereports.springeropen.com\/articles\/10.1186\/s40792-024-02033-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2033"],"URL":"https:\/\/doi.org\/10.1186\/s40792-024-02033-2","relation":{},"ISSN":["2198-7793"],"issn-type":[{"value":"2198-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"28 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"231"}}