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A Model to Predict Treatment Failure in Patients Undergoing Upfront Surgery for Resectable Colorectal Liver Metastases

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Introduction

Patients who recur in the first year after resection of colorectal liver metastases (CRLM) do poorly. The aim of our study was to predict treatment failure in patients undergoing upfront resection with a nomogram.

Methods

Data from patients resected between 1991 and 2019 were randomly split (70:30) into two cohorts. Treatment failure was defined as any recurrence or death within 12 months. A nomogram was constructed using multivariable logistic regression on the training cohort and validated using the testing cohort.

Results

Overall, 783 patients were included. Primary tumor characteristics included 50% left-sided: 75.2% T3/4 and 56.5% node-positive. The median disease-free interval was 10 months, median number of metastases was 1 (1–50), and with a median size of 3.6 cm (0.2–22); 222 (28.3%) patients recurred within 1 year. Recurrence was mostly extrahepatic with or without liver involvement (150/222, 67.6%). Curative-intent treatment was possible in 37.8% of these patients. Primary location, T-stage and node status, disease-free interval, and number and size of metastases were associated with treatment failure. The area under the curve from the validation of the model was 0.6 (95% confidence interval 0.52–0.68). Patients with a high-risk of treatment failure (≥40%) had a worse survival from the landmark time of 12 months from surgery compared with those with low-risk (2-years: 82% vs. 70%; p = 0.0002).

Conclusions

Primary location, T stage, node status, disease-free interval, and number and size of metastases are associated with treatment failure. The survival of patients with a probability of treatment failure ≥40% is unfavorable. Future trials investigating the role of neoadjuvant therapy in these high-risk patients are warranted.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

    Article  PubMed  Google Scholar 

  2. D’Angelica M, Kornprat P, Gonen M, et al. Effect on outcome of recurrence patterns after hepatectomy for colorectal metastases. Ann Surg Oncol. 2011;18(4):1096–103. https://doi.org/10.1245/s10434-010-1409-1

    Article  PubMed  Google Scholar 

  3. Liu W, Zhou JG, Sun Y, et al. The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis. Oncotarget. 2016;7(24):37277–87.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Vigano L, Russolillo N, Ferrero A, et al. Evolution of long-term outcome of liver resection for colorectal metastases: analysis of actual 5-year survival rates over two decades. Ann Surg Oncol. 2012;19(6):2035–44. https://doi.org/10.1245/s10434-011-2186-1

    Article  PubMed  Google Scholar 

  5. de Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250(3):440–8.

    Article  PubMed  Google Scholar 

  6. Kawaguchi Y, Vauthey JN. The landmark series: randomized control trials examining perioperative chemotherapy and postoperative adjuvant chemotherapy for resectable colorectal liver metastasis. Ann Surg Oncol. 2020;27(11):4263–70. https://doi.org/10.1245/s10434-020-08777-z

    Article  PubMed  Google Scholar 

  7. Araujo R, Gonen M, Allen P, et al. Comparison between perioperative and postoperative chemotherapy after potentially curative hepatic resection for metastatic colorectal cancer. Ann Surg Oncol. 2013;20(13):4312–21. https://doi.org/10.1245/s10434-013-3162-8

    Article  PubMed  Google Scholar 

  8. Nordlinger B, Sorbye H, Glimelius B, et al. 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. 2008;371(9617):1007–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nordlinger B, Sorbye H, Glimelius B, et al. 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. 2013;14(12):1208–15.

    Article  CAS  PubMed  Google Scholar 

  10. Benson AB, Venook AP, Al-Hawary MM, et al. NCCN Guidelines Insights: Rectal Cancer, Version 6.2020. J Natl Compr Canc Netw. 2020;18(7):806–15.

    Article  PubMed  Google Scholar 

  11. Benson AB, Venook AP, Al-Hawary MM, et al. NCCN guidelines insights: Colon Cancer Version 2.2018. J Natl Compr Canc Netw. 2018;16(4):359–69.

    Article  PubMed  Google Scholar 

  12. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422.

    Article  PubMed  Google Scholar 

  13. Chua TC, Saxena A, Liauw W, et al. Systematic review of randomized and nonrandomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol. 2010;17(2):492–501. https://doi.org/10.1245/s10434-009-0781-1

    Article  PubMed  Google Scholar 

  14. Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240(6):1052–61.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rubbia-Brandt L, Audard V, Sartoretti P, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15(3):460–6.

    Article  CAS  PubMed  Google Scholar 

  16. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24(13):2065–72.

    Article  CAS  PubMed  Google Scholar 

  17. Aloia T, Sebagh M, Plasse M, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006;24(31):4983–90.

    Article  CAS  PubMed  Google Scholar 

  18. Gallagher DJ, Zheng J, Capanu M, et al. Response to neoadjuvant chemotherapy does not predict overall survival for patients with synchronous colorectal hepatic metastases. Ann Surg Oncol. 2009;16(7):1844–51. https://doi.org/10.1245/s10434-009-0348-1

    Article  PubMed  Google Scholar 

  19. Tan MC, Butte JM, Gonen M, et al. Prognostic significance of early recurrence: a conditional survival analysis in patients with resected colorectal liver metastasis. HPB (Oxford). 2013;15(10):803–13.

    Article  PubMed  Google Scholar 

  20. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lalmahomed ZS, Mostert B, Onstenk W, et al. Prognostic value of circulating tumour cells for early recurrence after resection of colorectal liver metastases. Br J Cancer. 2015;112(3):556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sorbye H. Recurrence patterns after resection of liver metastases from colorectal cancer. Recent Results Cancer Res. 2014;203:243–52.

    Article  PubMed  Google Scholar 

  23. Liu W, Wang HW, Wang K, et al. The primary tumor location impacts survival outcome of colorectal liver metastases after hepatic resection: A systematic review and meta-analysis. Eur J Surg Oncol. 2019;45(8):1349–56.

    Article  PubMed  Google Scholar 

  24. Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: Issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87.

    Article  PubMed  Google Scholar 

  25. Austin PC, Steyerberg EW. Interpreting the concordance statistic of a logistic regression model: Relation to the variance and odds ratio of a continuous explanatory variable. BMC Med Res Methodol. 2012;12:82.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nordlinger B, Van Cutsem E, Gruenberger T, et al. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: Recommendations from an expert panel. Ann Oncol. 2009;20(6):985–92.

    Article  CAS  PubMed  Google Scholar 

  27. Abdalla EK, Vauthey JN. Chemotherapy prior to hepatic resection for colorectal liver metastases: Helpful until harmful? Dig Surg. 2008;25(6):421–9.

    Article  CAS  PubMed  Google Scholar 

  28. Zorzi D, Laurent A, Pawlik TM, et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94(3):274–86.

    Article  CAS  PubMed  Google Scholar 

  29. Adam R, Bhangui P, Poston G, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252(5):774–87.

    Article  PubMed  Google Scholar 

  30. Lehmann K, Rickenbacher A, Weber A, et al. Chemotherapy before liver resection of colorectal metastases: Friend or foe? Ann Surg. 2012;255(2):237–47.

    Article  PubMed  Google Scholar 

  31. Jarnagin WR, D’Angelica M. Systemic therapy for patients with resectable hepatic colorectal metastases: Improving patient selection. Ann Surg Oncol. 2014;21(1):11–2. https://doi.org/10.1245/s10434-013-3312-z

    Article  PubMed  Google Scholar 

  32. Malik HZ, Gomez D, Wong V, et al. Predictors of early disease recurrence following hepatic resection for colorectal cancer metastasis. Eur J Surg Oncol. 2007;33(8):1003–9.

    Article  CAS  PubMed  Google Scholar 

  33. Kaibori M, Iwamoto Y, Ishizaki M, et al. Predictors and outcome of early recurrence after resection of hepatic metastases from colorectal cancer. Langenbecks Arch Surg. 2012;397(3):373–81.

    Article  PubMed  Google Scholar 

  34. Bhogal RH, Hodson J, Bramhall SR, et al. Predictors of early recurrence after resection of colorectal liver metastases. World J Surg Oncol. 2015;13:135.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Takahashi S, Konishi M, Nakagohri T, et al. Short time to recurrence after hepatic resection correlates with poor prognosis in colorectal hepatic metastasis. Jpn J Clin Oncol. 2006;36(6):368–75.

    Article  PubMed  Google Scholar 

  36. Vigano L, Capussotti L, Lapointe R, et al. Early recurrence after liver resection for colorectal metastases: risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6,025 patients. Ann Surg Oncol. 2014;21(4):1276–86. https://doi.org/10.1245/s10434-013-3421-8

    Article  PubMed  Google Scholar 

  37. Imai K, Allard MA, Benitez CC, et al. early recurrence after hepatectomy for colorectal liver metastases: What optimal definition and what predictive factors? Oncologist. 2016;21(7):887–94.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ayez N, van der Stok EP, de Wilt H, et al. 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. 2015;15:180.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Neal CP, Garcea G, Doucas H, et al. Molecular prognostic markers in resectable colorectal liver metastases: A systematic review. Eur J Cancer. 2006;42(12):1728–43.

    Article  CAS  PubMed  Google Scholar 

  40. Brudvik KW, Jones RP, Giuliante F, et al. RAS mutation clinical risk score to predict survival after resection of colorectal liver metastases. Ann Surg. 2019;269(1):120–6.

    Article  PubMed  Google Scholar 

  41. Newhook TE, Overman MJ, Chun YS, et al. Prospective study of perioperative circulating tumor DNA dynamics in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2022. https://doi.org/10.1097/SLA.0000000000005461.

    Article  PubMed  Google Scholar 

  42. Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med. 1999;341(27):2039–48.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Giammauro Berardi MD, PhD, FEBS (HPB), Vinod P. Balachandran MD, Jeffrey Drebin MD, PhD, William R. Jarnagin MD, T. Peter Kingham MD, Kevin C. Soares MD, Alice Wei MD & Michael D’Angelica MD

  2. Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Joanne Chou MPH & Mithat Gonen PhD

Authors
  1. Giammauro Berardi MD, PhD, FEBS (HPB)
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Correspondence to Giammauro Berardi MD, PhD, FEBS (HPB).

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Berardi, G., Chou, J., Gonen, M. et al. A Model to Predict Treatment Failure in Patients Undergoing Upfront Surgery for Resectable Colorectal Liver Metastases. Ann Surg Oncol 30, 2820–2827 (2023). https://doi.org/10.1245/s10434-023-13113-2

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