Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial

Bruzzi, Matthieu; Auclin, Édouard; Dico, R. Lo; Voron, Thibault; Karoui, Mehdi; Espín, Eloy; Cianchi, Fabio; Weitz, Juergen; Buggenhout, Alexis; Malafosse, Robert; Denimal, F.; Malicot, Karine Le; Vernerey, Déwi; Douard, Richard; Emile, Jean François; Lepage, Côme; Laurent‐Puig, Pierre; Taieb, Julien

doi:10.1245/s10434-019-07513-6

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…Recurrence rate was higher in RAS/BRAF positive patients compared to wild type patients, but the RAS/BRAF mutational status was not associated with a speci c relapse site. In addition, no signi cant difference was found regarding the site of recurrence between KRAS and NRAS mutant cases [17]. Since there was only one NRAS negative patient in the early stage in our study, its effect on the relapse pattern could not be clearly evaluated.…”

Section: Discussionmentioning

confidence: 70%

“…It is known that the RAS and BRAF mutation status has a predictive importance in the use of targeted therapies together with chemotherapy in the treatment of end-stage colon cancer, and the presence of mutation adversely affects the prognosis of the disease [9]. But studies investigating the effect of the presence of mutation on the course of the disease in early stage colon cancer are limited.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers

Kunt

Araz

Yıldırım

et al. 2023

J Gastrointest Canc

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It is known that the RAS and BRAF mutations are predictive for targeted therapies together with chemotherapy in the treatment of metastatic colon cancer and affect negatively the prognosis of the disease. In early stage cancer, however, there are limited studies in the literature about the relationship of this mutational condition with prognosis and relapse pattern of the disease. In this study, in addition to classical risk factors, we evaluated the effects of mutational status on the clinical pattern at recurrence and survival in early stage colon cancer. MethodsPatients who diagnosed with early-stage colon cancer and when following up recurrence or metastasis was detected were included in this study. Patients were divided into two groups as positive and negative RAS/BRAF mutations. Mutation analysis was performed from the early stage tissue of the patients whose mutation was positive at the time of recurrence. The relationship between mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed. ResultsThe number of patients with positive and negative mutations in the early stage were 39 and 40, respectively. 69% of the patients in the mutant group and 70% of the patients in the wild group were in stage 3. Both OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically signi cantly lower in mutant patients. Most patients had distant metastases at the time of recurrence on both sides (61.5% vs. 62.5%, respectively). There was no signi cant difference between mutant and non-mutant patients in terms of distant metastasis and local recurrence rates (p = 0.657). In the mutation re-analysis performed from the early stage tissue of the patients with mutations in the metastatic period, 11.4% of the patients were found to have no mutations. ConclusionPresence of mutation in early stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a signi cant effect on the recurrence pattern. Because of the discordance of earlystage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse, if possible.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers

Kunt

Araz

Yıldırım

et al. 2023

J Gastrointest Canc

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“…Nevertheless, we found a poor median survival of 17.6 months after relapse, consistent with the results observed in patients with resected stage III or IV colorectal tumors [ 36 , 37 ]. The poor OS after relapse might have resulted from the fact that more than half of patients often develop the recurrent disease at multiple sites, which was confirmed to be an indicator of poor survival after recurrence [ 38 ]. Moreover, the rate of liver-limited or lung-limited recurrence reached almost 30%, suggesting that an aggressive adjuvant therapeutic strategy, for example, the intra-arterial chemotherapy, should therefore be developed to prevent post-LRIs recurrence, and repeated LRIs are likely to improve the survival of such patients after a novel effective systemic treatment.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Locoregional Interventions for BRAF V600E Metastatic Colorectal Cancer: A Retrospective Cohort Analysis

Ren

et al. 2021

Biomolecules

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The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22–0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01–1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04–0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21–1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM.

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“…However, single-agent 5-FU-based chemotherapy may be less efficacious in patients with LS, and no survival benefit is seen in stage II MMR-deficient patients, even in the setting of other high-risk features [71]. Interestingly, although CRCs with mutated MMR genes present more commonly with poor differentiation and mucinous features, LS patients experience better stage-matched survival and fewer recurrences compared to sporadic cancers, particularly for cancers in the proximal colon [69,70,72,73]. As mentioned above, MMRdeficient cancers express high levels of tumor-related neoantigens, prompting increased TIL presence [49].…”

Section: Medical Treatmentmentioning

confidence: 99%

Sporadic and Inherited Colorectal Cancer: How Epidemiology and Molecular Biology Guide Screening and Treatment

Glasgow

Hardiman

2021

The ASCRS Textbook of Colon and Rectal Surgery

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Colorectal cancer is caused by the accumulation of a variety of genetic alterations in colonic mucosa. • Colorectal cancer can be hereditary or sporadic (not inherited). Both forms share many of the same genetic alterations. • Multiple hereditary forms of colorectal cancer have an expected phenotype due to the genetic alteration that increases the likelihood of the cancer. • Screening algorithms for colorectal cancer differ between hereditary and sporadic cancer based on the time expected for an adenoma to become a carcinoma in that patient. • Hereditary forms of colorectal cancer are more commonly seen in patients with young onset colorectal cancer. • Treatment algorithms for hereditary colorectal cancer are directed towards removal of the cancer and decreasing future risk of additional cancers.

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Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial

Abstract: Background. Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAF V600E status in stage III CC patients.

Cited by 11 publications

References 25 publications

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers

The Prognostic Value of Locoregional Interventions for BRAF V600E Metastatic Colorectal Cancer: A Retrospective Cohort Analysis

Sporadic and Inherited Colorectal Cancer: How Epidemiology and Molecular Biology Guide Screening and Treatment

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