Evaluating Combinations of Biological and Clinicopathologic Factors Linked to Poor Outcomes in Resected Colorectal Liver Metastasis: An External Validation Study

期刊论文
发表日期：

2024年10月8日

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Kazunari Sasaki,
Jane Wang,
Carsten Kamphues,
Stefan Buettner,
Johan Gagniere,
Victoria Ardilles,
Katsunori Imai,
Doris Wagner,
Ioannis Pozios,
Dimitris Papakonstantinou,
Emmanouil Pikoulis,
Efstathios Antoniou,
Daisuke Morioka,
Inger Marie Løes,
Per Eystein Lønning,
Peter Kornprat,
Federico N. Aucejo,
Hideo Baba,
Eduardo de Santibañes,
Klaus Kaczirek,
Richard Burkhart,
Itaru Endo,
Katharina Beyer,
Martin E. Kreis,
Timothy M. Pawlik,
Georgios Antonios Margonis

摘要

Background

Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be “biologically” futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies.

Patients and Methods

We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes.

Results

The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months.

Conclusion

The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease.