nach oben

International Journal of Clinical Oncology

Erschienen in:

14.09.2021 | Original Article

Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases

verfasst von: Mizuki Ninomiya, Yasunori Emi, Takashi Motomura, Takahiro Tomino, Tomohiro Iguchi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Takashi Nishizaki, Hidefumi Higashi, Hiroyuki Kuwano

Erschienen in: International Journal of Clinical Oncology | Ausgabe 12/2021

Einloggen, um Zugang zu erhalten

Abstract

Background

The role of preoperative neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CRLM) remains undetermined. This study aimed to assess the efficacy of NAC in patients with resectable CRLM, especially in high-risk subgroups for recurrence, with special reference to synchronicity and the CRLM grade in the Japanese classification system.

Methods

A retrospective analysis of a multi-institutional cohort who was diagnosed with resectable CRLM was performed. CRLM was classified into three grades (A, B, and C) according to the combination of H stage (H1: ≤ 4 lesions and ≤ 5 cm, H2: ≥ 5 lesions or > 5 cm, H3: ≥ 5 lesions and > 5 cm), nodal status of the primary tumor (pN0/1: ≤ 3 metastases, pN2: ≥ 4 metastases), and the presence of resectable extrahepatic metastases.

Results

Among 222 patients with resectable CRLM, 97 (43.7%) had synchronous CRLM. The surgical failure-free survival (SF-FS) of patients with synchronous CRLM (without NAC) was significantly worse than that of patients with metachronous CRLM (P = 0.0264). The SF-FS of patients with Grade B/C was also significantly worse than that of Grade A (P = 0.0058). Among the 53 patients with synchronous and Grade B/C CRLM, 31 were assigned to NAC, and all of them underwent liver surgery. In this high-risk subgroup, the SF-FS and OS in the NAC group were significantly better than those in the upfront surgery group (P < 0.0001 and P = 0.0004, respectively).

Conclusions

Patients with synchronous and Grade B/C CRLM could be good candidates for indication of NAC.

Nur mit Berechtigung zugänglich

Hallet J, Sa Cunha A, Adam R et al (2016) Factors influencing recurrence following initial hepatectomy for colorectal liver metastases. Br J Surg 103:1366–1376. https://doi.org/10.1002/bjs.10191CrossRefPubMed

Primrose J, Falk S, Finch-Jones M et al (2014) Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial. Lancet Oncol 15:601–611. https://doi.org/10.1016/S1470-2045(14)70105-6CrossRefPubMed

Kopetz S, Chang GJ, Overman MJ et al (2009) Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 27:3677–3683. https://doi.org/10.1200/JCO.2008.20.5278CrossRefPubMedPubMedCentral

Saiura A, Yamamoto J, Hasegawa K et al (2012) Liver resection for multiple colorectal liver metastases with surgery up-front approach: bi-institutional analysis of 736 consecutive cases. World J Surg 36:2171–2178. https://doi.org/10.1007/s00268-012-1616-yCrossRefPubMed

Hebbar M, Pruvot FR, Romano O et al (2009) Integration of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases from colorectal cancer. Cancer Treat Rev 35:668–675. https://doi.org/10.1016/j.ctrv.2009.08.005CrossRefPubMed

Folprecht G, Gruenberger T, Bechstein WO et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11:38–47. https://doi.org/10.1016/S1470-2045(09)70330-4CrossRefPubMed

Beppu T, Emi Y, Tokunaga S et al (2014) Liver resectability of advanced liver-limited colorectal liver metastases following mFOLFOX6 with bevacizumab (KSCC0802 study). Anticancer Res 34:6655–6662PubMed

Oki E, Emi Y, Yamanaka T et al (2019) Randomised phase II trial of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab as first-line treatment for colorectal liver metastasis (ATOM trial). Br J Cancer 121:222–229. https://doi.org/10.1038/s41416-019-0518-2CrossRefPubMedPubMedCentral

Wang ZM, Chen YY, Chen FF et al (2015) Peri-operative chemotherapy for patients with resectable colorectal hepatic metastasis: a meta-analysis. Eur J Surg Oncol 41:1197–1203. https://doi.org/10.1016/j.ejso.2015.05.020CrossRefPubMed

10.

Bonney GK, Coldham C, Adam R et al (2015) Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; an international multi-center data analysis using LiverMetSurvey. J Surg Oncol 111:716–724. https://doi.org/10.1002/jso.23899CrossRefPubMed

11.

Zhu D, Zhong Y, Wei Y et al (2014) Effect of neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. PLoS ONE 9:1–6. https://doi.org/10.1371/journal.pone.0086543CrossRef

12.

Hirokawa F, Asakuma M, Komeda K et al (2019) Is neoadjuvant chemotherapy appropriate for patients with resectable liver metastases from colorectal cancer? Surg Today 49:82–89. https://doi.org/10.1007/s00595-018-1716-xCrossRefPubMed

13.

Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 371:1007–1016. https://doi.org/10.1016/S0140-6736(08)60455-9CrossRefPubMedPubMedCentral

14.

Nordlinger B, Sorbye H, Glimelius B et al (2013) Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 14:1208–1215. https://doi.org/10.1016/S1470-2045(13)70447-9CrossRefPubMed

15.

Ichida H, Mise Y, Ito H et al (2019) Optimal indication criteria for neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. World J Surg Oncol 17:1–9. https://doi.org/10.1186/s12957-019-1641-5CrossRef

16.

Yamaguchi T, Mori T, Takahashi K et al (2008) A new classification system for liver metastases from colorectal cancer in Japanese multicenter analysis. Hepatogastroenterology 55:173–178PubMed

17.

Shinto E, Takahashi K, Yamaguchi T et al (2015) Validation and modification of the Japanese Classification System for liver metastases from colorectal cancer: a multi-institutional study. Ann Surg Oncol 22:3888–3895. https://doi.org/10.1245/s10434-015-4470-yCrossRefPubMed

18.

Yamashita K, Watanabe M, Mine S et al (2018) The impact of the Charlson comorbidity index on the prognosis of esophageal cancer patients who underwent esophagectomy with curative intent. Surg Today 48:632–639. https://doi.org/10.1007/s00595-018-1630-2CrossRefPubMed

19.

Hwang M, Jayakrishnan TT, Green DE et al (2014) Systematic review of outcomes of patients undergoing resection for colorectal liver metastases in the setting of extra hepatic disease. Eur J Cancer 50:1747–1757. https://doi.org/10.1016/j.ejca.2014.03.277CrossRefPubMed

20.

Oba M, Hasegawa K, Shindoh J et al (2016) Survival benefit of repeat resection of successive recurrences after the initial hepatic resection for colorectal liver metastases. Surgery 159:632–640. https://doi.org/10.1016/j.surg.2015.09.003CrossRefPubMed

21.

Oba M, Hasegawa K, Matsuyama Y et al (2014) Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure. Ann Surg Oncol 21:1817–1824. https://doi.org/10.1245/s10434-014-3504-1CrossRefPubMed

22.

Allard MA, Nishioka Y, Beghdadi N et al (2019) Multicentre study of perioperative versus adjuvant chemotherapy for resectable colorectal liver metastases. BJS open 3:678–686. https://doi.org/10.1002/bjs5.50174CrossRefPubMed

23.

Ratti F, Fuks D, Cipriani F et al (2019) Timing of perioperative chemotherapy does not influence long-term outcome of patients undergoing combined laparoscopic colorectal and liver resection in selected upfront resectable synchronous liver metastases. World J Surg 43:3110–3119. https://doi.org/10.1007/s00268-019-05142-4CrossRefPubMed

24.

Hewes JC, Dighe S, Morris RW et al (2007) Preoperative chemotherapy and the outcome of liver resection for colorectal metastases. World J Surg 31:353–364. https://doi.org/10.1007/s00268-006-0103-8CrossRefPubMed

25.

Nishioka Y, Shindoh J, Yoshioka R et al (2017) Clinical impact of preoperative chemotherapy on microscopic cancer spread surrounding colorectal liver metastases. Ann Surg Oncol 24:2326–2333. https://doi.org/10.1245/s10434-017-5845-zCrossRefPubMed

26.

Beppu T, Sakamoto Y, Hasegawa K et al (2012) A nomogram predicting disease-free survival in patients with colorectal liver metastases treated with hepatic resection: multicenter data collection as a project study for hepatic surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 19:72–84. https://doi.org/10.1007/s00534-011-0460-zCrossRefPubMed

27.

Okuno M, Hatano E, Seo S et al (2014) Indication for neoadjuvant chemotherapy in patients with colorectal liver metastases based on a nomogram that predicts disease-free survival. J Hepatobiliary Pancreat Sci 21:881–888. https://doi.org/10.1002/jhbp.149CrossRefPubMed

28.

Ayez N, van der Stok EP, de Wilt H et al (2015) Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial. BMC Cancer 15:1–7. https://doi.org/10.1186/s12885-015-1199-8CrossRef

Titel: Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases
verfasst von: Mizuki Ninomiya
Yasunori Emi
Takashi Motomura
Takahiro Tomino
Tomohiro Iguchi
Hiroto Kayashima
Noboru Harada
Hideaki Uchiyama
Takashi Nishizaki
Hidefumi Higashi
Hiroyuki Kuwano
Publikationsdatum: 14.09.2021
Verlag: Springer Singapore
Erschienen in: International Journal of Clinical Oncology / Ausgabe 12/2021
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-021-02024-5

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases