Prognostic Significance of Surgical Margin Size After Neoadjuvant FOLFOX and/or FOLFIRI for Colorectal Liver Metastases

J Gastrointest Surg. 2017 Nov;21(11):1831-1840. doi: 10.1007/s11605-017-3557-0. Epub 2017 Sep 7.

Abstract

Purpose: Optimal margin size when resecting colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin size in patients who received neoadjuvant FOLFOX and/or FOLFIRI prior to resection of CRLM.

Methods: Clinicopathologic factors were collected for patients who underwent curative liver resections for CRLM between 4/2004-1/2016 and received neoadjuvant oxaliplatin and/or irinotecan and 5-FU (FOLFOX, FOLFIRI). Margins were categorized as < 1, ≥ 1-< 5, ≥ 5-< 10, or ≥ 10 mm and evaluated for association with overall survival (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (< 1 mm) or negative (≥ 1 mm) and similarly evaluated.

Results: Of 227 patients, the median age was 58 years and most had synchronous (80%) lesions. The majority had colon cancers (75%). Margin sizes were 13% < 1 mm, 27% ≥ 1-< 5 mm, 23% ≥ 5-< 10 mm, 36% ≥ 10 mm. Most (63%) received chemotherapy post-liver resection. Five-year OS and DFS were 54% (95% CI 46-62%) and 22% (95% CI 16-28%), respectively. Positive margins significantly increased the risk of death without post-liver resection chemotherapy (HR = 3.32, p = 0.0077), but not with post-liver resection chemotherapy (HR = 1.00, p = 0.99). Negative margin sizes of ≥ 1-< 5, ≥ 5-< 10, and ≥ 10 mm were not significant predictors of OS (p > 0.05).

Conclusion: Patients undergoing liver resection for CRLM should receive post-resection chemotherapy if negative margins (≥ 1 mm) cannot be achieved. For patients receiving FOLFOX and/or FOLFIRI chemotherapy, wider margins did not improve OS.

Keywords: Colorectal liver metastases; Neoadjuvant chemotherapy; Surgical margin.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use
  • Hepatectomy
  • Humans
  • Irinotecan
  • Leucovorin / therapeutic use
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Margins of Excision*
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Prognosis
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol