Contour prognostic model for predicting survival after resection of colorectal liver metastases: development and multicentre validation study using largest diameter and number of metastases with <i>RAS</i> mutation status

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.

Section: Ras Mutations and Prognosis After Crlm Treatmentmentioning

confidence: 99%

Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases

Rhaiem

Rached

Tashkandi

et al. 2022

“…The CRS is included for reference as most prognostic models used the CRS to compare the performance of their models [11]. Twelve prognostic models incorporating RAS mutation status as a predictor of outcomes after resection of CRLM have been published since 2017 [19][20][21][22][23][24][25][26][27][28][29][30]. Ten models were developed and validated by including patients from 2000 onwards, which parallels key developments in systemic chemotherapy such as the introduction of irinotecan and oxaliplatin as components of cytotoxic combination therapy and the use of biological agents such as bevacizumab, cetuximab, and panitumumab [4].…”

Section: Prognostic Models Incorporating Ras Mutation Statusmentioning

confidence: 99%

“…Although the most recent, largest, and longest longitudinal study to date by Buisman et al, 2020 included patients from a long inclusion period (1992-2019) to estimate 10-year overall survival, the cohort largely reflects contemporary patient selection and treatment as most patients (82.0%) underwent resection after 2000 [30]. Nine studies included a validation cohort [21][22][23][25][26][27][28][29][30]. The predicted outcome was overall survival in eight studies and recurrence-free survival in four studies.…”

Section: Prognostic Models Incorporating Ras Mutation Statusmentioning

confidence: 99%

“…At the other end of the spectrum, a C-statistic of one indicates that the prediction model always discriminates against patients who experience the outcome compared to those who do not [32]. The model by Buisman et al to predict 10-year overall survival documented the highest C-statistic (0.73) in its development cohort, while the remaining nine studies reported a C-statistic between 0.6 and 0.7 [20][21][22][23][25][26][27][28][29][30]. Calibration refers to a model's accuracy of risk estimates and indicates the extent to which expected and observed outcomes agree [33].…”

Section: Assessing the Performance Of Prediction Models Incorporating...mentioning

confidence: 99%

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Prognostic Models Incorporating RAS Mutation to Predict Survival in Patients with Colorectal Liver Metastases: A Narrative Review

Wong

Diakos

Molloy

et al. 2022

Recurrence and survival vary widely among patients who undergo curative-intent resection of colorectal liver metastases (CRLM). Prognostic models provide estimated probabilities of these outcomes and allow the effects of multiple potentially interacting variables to be adjusted and assessed simultaneously. Although many prognostic models based on clinicopathologic factors have been developed since the 1990s to predict survival after resection of CRLM, these models vary in their predictive performance when applied to contemporary cohorts. Rat sarcoma viral oncogene homolog (RAS) mutation status is routinely tested in patients with metastatic colorectal cancer to predict response to anti-epidermal growth factor therapy. In addition, mutations in RAS predict survival and recurrence in patients undergoing hepatectomy for CRLM. Several recent prognostic models have incorporated RAS mutation status as a surrogate of tumor biology and combined revised clinicopathologic variables to improve the prediction of recurrence and survival. This narrative review aims to evaluate the differences between contemporary prognostic models incorporating RAS mutation status and their clinical applicability in patients considered for curative-intent resection of CRLM.

“…Of note, many of the current prognostic models lack external validation, which can inform whether a model can be generalized outside the cohort that was used to train it. Furthermore, the plethora of new prognostic models that incorporate genetic information mandates studies that will compare model performance [ 9 , 10 , 11 , 12 ].…”

mentioning

confidence: 99%

Prognostic and Therapeutic Implications of Tumor Biology in Colorectal Liver Metastases

Kamphues

Beyer

Margonis

2021

Prognostic models allow clinicians to predict survival outcomes, facilitate patient–physician discussions, and identify subgroups with potentially distinct prognoses. Although such prognostic stratification cannot directly predict treatment benefit, it can help to inform clinical decision making. This editorial will discuss potential avenues for these topics in the context of colorectal cancer liver metastases (CRLM)[...]