Dataset Information

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

ABSTRACT:

Background

Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied.

Methods

This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status.

Results

Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups.

Conclusions

There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status.

Clinical trial registration

NCT01531621/EudraCT2011-003158-24.

SUBMITTER: Uutela A

PROVIDER: S-EPMC9381729 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

Uutela Aki A Osterlund Emerik E Halonen Päivi P Kallio Raija R Ålgars Annika A Salminen Tapio T Lamminmäki Annamarja A Soveri Leena-Maija LM Ristamäki Raija R Lehtomäki Kaisa K Stedt Hanna H Heervä Eetu E Muhonen Timo T Kononen Juha J Nordin Arno A Ovissi Ali A Kytölä Soili S Keinänen Mauri M Sundström Jari J Nieminen Lasse L Mäkinen Markus J MJ Kuopio Teijo T Ristimäki Ari A Isoniemi Helena H Osterlund Pia P

British journal of cancer 20220524 4

<h4>Background</h4>Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied.<h4>Methods</h4>This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status.<h4>Results</h4>P ...[more]

PMID: 35610367

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Project description:Colorectal cancer (CRC) patients frequently develop liver metastases. Different treatment strategies are available according to the timing of appearance, the burden of metastatic disease, and the performance status of the patient. Systemic treatment (ST) represents the cornerstone of metastatic disease management. However, in select cases, combined ST and surgical resection can lead to remarkable survival outcomes. In the present multicentric cohort study, we explored the efficacy of a conversion strategy in a selected population of left-sided RAS/BRAF wild-type CRC patients with liver-limited metastatic disease.MethodsThe primary endpoint was to compare survival outcomes of patients undergoing ST not leading to surgery, liver resection after conversion ST, and hepatic resection with perioperative ST. Furthermore, we explored survival outcomes depending on whether the case was discussed within a multidisciplinary team.ResultsBetween 2012 and 2020, data from 690 patients respecting the inclusion criteria were collected. Among these, 272 patients were deemed eligible for the analysis. The conversion rate was 24.1% of cases. Fifty-six (20.6%) patients undergoing surgical resection after induction treatment (i.e., ultimately resectable) had a significant survival advantage compared to those receiving systemic treatment not leading to surgery (176 pts, 64.7%) (5-year OS 60.8% and 11.7%, respectively, Log Rank test p < 0.001; HR = 0.273; 95% CI: 0.16-0.46; p < 0.001; 5-year PFS 22.2% and 6.3%, respectively, Log Rank test p < 0.001; HR = 0.447; 95% CI: 0.32-0.63; p < 0.001). There was no difference in survival between ultimately resectable patients and those who had liver resection with perioperative systemic treatment (potentially resectable-40 pts) (5-year OS 71.1%, Log Rank test p = 0.311. HR = 0.671; 95% CI: 0.31-1.46; p = 0.314; 5-year PFS 25.7%, Log Rank test p = 0.305. HR = 0.782; 95% CI: 0.49-1.25; p = 0.306).ConclusionsIn our selected population of left-sided RAS/BRAF wild-type colorectal cancer patients with liver-limited disease, a conversion strategy was confirmed to provide a survival benefit. Patients not deemed surgical candidates at the time of diagnosis and patients judged resectable with perioperative systemic treatment have similar survival outcomes.

Project description:ImportanceAspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2), suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type neoplastic cells.ObjectiveTo examine whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation.Design and settingWe collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 1, 2006, for cancer incidence and until January 1, 2012, for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for colorectal carcinoma incidence according to BRAF mutation status.Main outcomes and measuresIncidence of colorectal cancer cases according to tumor BRAF mutation status.ResultsAmong 127,865 individuals, with 3,165,985 person-years of follow-up, we identified 1226 incident rectal and colon cancers with available molecular data. Compared with nonuse, regular aspirin use was associated with lower BRAF-wild-type cancer risk (multivariable HR, 0.73; 95% CI, 0.64 to 0.83; age-adjusted incidence rate difference [RD], -9.7; 95% CI, -12.6 to -6.7 per 100,000 person-years). This association was observed irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation. In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer (multivariable HR, 1.03; 95% CI, 0.76 to 1.38; age-adjusted, incidence RD, 0.7; 95% CI, -0.3 to 1.7 per 100,000 person-years: P for heterogeneity = .037, between BRAF-wild-type vs BRAF-mutated cancer risks). Compared with no aspirin use, aspirin use of more than 14 tablets per week was associated with a lower risk of BRAF-wild-type cancer (multivariable HR, 0.43; 95% CI, 0.25 to 0.75; age-adjusted incidence RD, -19.8; 95% CI, -26.3 to -13.3 per 100,000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (P for heterogeneity = .005).Conclusions and relevanceRegular aspirin use was associated with lower risk of BRAF-wild-type colorectal cancer but not with BRAF-mutated cancer risk. These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin. Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings.

Dataset Information

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

Similar Datasets

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