Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations

Renaud, Stéphane; Seitlinger, Joseph; Lawati, Yaseen Al; Guerrera, Francesco; Falcoz, Pierre‐Emmanuel; Massard, Gilbert; Ferri, Lorenzo; Spicer, Jonathan

doi:10.1097/sla.0000000000002829

Cited by 34 publications

(29 citation statements)

References 34 publications

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“…Patients with wild‐type tumors had a similar risk of recurrence irrespective of the surgical technique. Similarly, Renaud et al found that KRAS patients who underwent lung metastasectomy had a lower risk of pulmonary recurrence and longer survival. Patients with wild‐type tumors had a similar risk of recurrence irrespective of the surgical technique (anatomical vs nonanatomical).…”

Section: Resultsmentioning

confidence: 91%

Mutation status and surgical selection

Margonis

Kreis

Wolfgang

et al. 2019

Journal of Surgical Oncology

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Current evidence cannot support denying metastasectomy in otherwise resectable patients solely based on their overall KRAS or BRAF mutational status. The combination of KRAS or BRAF mutational status with certain clinicopathologic characteristics has defined groups of patients who may not derive benefit from metastasectomy, but external validation is needed. The effect of certain KRAS or BRAF variants on survival may be more pronounced and therefore future studies should consider them for surgical selection.

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Section: Resultsmentioning

confidence: 91%

Mutation status and surgical selection

Margonis

Kreis

Wolfgang

et al. 2019

Journal of Surgical Oncology

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“…The histology and genotype of the primary tumor are among the most important factors in prognosis and survival after PM. The mechanism of metastasis varies depending on the histological type of the tumor: colorectal metastases have a high rate of pleural invasion, and of interstitial and aerogenous spread of floating cancer cells, which are in turn associated with a high rate of local recurrence [24]. Melanoma does not show pleural invasion, but is associated with a higher probability of perivascular growth and an increased incidence of lymphangitic spread [25].…”

Section: Discussionmentioning

confidence: 99%

Which factors significantly reduce long-term survival after pulmonary metastasectomy?

Seyrek¹,

Cansever²,

Bedirhan³

2021

Curr Thorac Surg

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Background: In this study, a survival analysis was performed of patients who underwent pulmonary metastasectomy over the past 10 years in our clinic. We aimed to elucidate the factors that significantly affected overall survival and identify subgroups of patients who may not benefit from pulmonary metastasectomy. Materials and Methods: We retrospectively reviewed 68 patients with a history of extra-thoracic malignancy who underwent pulmonary metastasectomy between January 2009 and December 2018. The overall survival rate was analyzed according to age, sex, histological type of the primary tumor, metastatic side, surgical approach type, pulmonary resection type, number of nodules resected, diseasefree interval, and nodal status. Results: The actuarial survival rate after pulmonary metastasectomy was 78% (95% confidence interval [CI]: 71-84) at 2 years and 48% (95% CI: 41-52) at 5 years. Patients with disease free interval < 12 months had a far worse survival rate (p = 0.001). Patients with sarcoma had a significantly worse prognosis than those with epithelial tumors or melanoma (p = 0.001). Patients with negative nodal status had a significantly better prognosis (p = 0.001), while patients with metastatic hilar lymph nodes also had significantly better survival compared to patients with metastatic mediastinal lymph nodes (N2) (p = 0.001). Conclusions: Tumor histology is the main determinant of overall survival and prognosis after pulmonary metastasectomy. The presence of multiple metastases in different unilateral lobes and N2 disease appeared to be the worst prognostic factors. Patients with either of these two significant negative prognostic factors should be evaluated carefully via a multidisciplinary approach and pulmonary metastasectomy should be performed only in selected patients.

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“…(95%CI:55%-58% , I 2 :97.6) for WT and mKRAS groups respectively. The overall prevalence of thoracic metastases based on four articles (24,25,27,28) was 20%(95%CI:16%-24% , I 2 :80.7) and 22%…”

Section: Sub-group Analysismentioning

confidence: 99%

KRAS and BRAF Mutations as survival prognostic factors for Metastatic Colorectal Cancer patients after Lung metastasectomy: A Systematic Review and Meta-Analysis

Shahramian¹,

Parooie²,

Salarzaei³

2020

Preprint

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Introduction While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. Therefore, in this paper, we conduct a systematic review and meta-analysis of retrospective and prospective studies to evaluate whether KRAS or BRAF mutation status can be independent predictors in colorectal cancer patients undergoing complete lung metastasis surgery.Methods A systematic literature review was performed to identify articles reporting overall survival (OS) of patients who underwent lung metastasectomy for colorectal cancer lung metastases (CRLM), stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis.Results 9 studies, including 1833 patients, were eligible for the meta-analysis. Based on the random effect model, the total frequency of KRAS mutations in 1305 patients who had undergone the lung metastasectomy was 45% and the total 5-year OS in these patients was 55.7%. five of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). the rate of KRAS mutations were lower in the studies with higher male to female ratio. There was statistically significant linear trend in univariate meta-regression to explain effect size variation by male to female ratio of study with coefficient = 0.47 (95% CI 0.03, 0.91), P = 0.03. disease free survival (DFS), thoracic metastases and origin of primary tumor were significantly influenced by KRAS mutation status.Conclusions Our meta-analysis confirms the KRAS mutation as a strong and predictive biomarker which makes overall survival lower in patients with colorectal cancer undergoing pulmonary metastasis surgery. Certainly, this interesting evidence represents the first step towards a deeper understanding of the molecular mechanisms underlying tumor behavior and patient outcomes in a subgroup of clinically selected colorectal cancer patients. By considering tumor molecular characteristics and other clinical-pathological factors, our results confirm the use of new therapeutic models to predict outcomes of patients undergoing colorectal lung metastasis surgery and to isolate both systemic and loco-regional treatment strategies.

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Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations

Abstract: AR seems to improve both the OS and TTPR in LM of CRC harboring KRAS mutations.

Cited by 34 publications

References 34 publications

Mutation status and surgical selection

Mutation status and surgical selection

Which factors significantly reduce long-term survival after pulmonary metastasectomy?

KRAS and BRAF Mutations as survival prognostic factors for Metastatic Colorectal Cancer patients after Lung metastasectomy: A Systematic Review and Meta-Analysis

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