Dataset Information

Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment.

ABSTRACT:

Objective

Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown.

Design

We conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up.

Results

The RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type.

Conclusion

This prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.

SUBMITTER: Wang F

PROVIDER: S-EPMC9185813 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment.

Wang Feng F Huang You-Sheng YS Wu Hao-Xiang HX Wang Zi-Xian ZX Jin Ying Y Yao Yi-Chen YC Chen Yan-Xing YX Zhao Qi Q Chen Shifu S He Ming-Ming MM Luo Hui-Yan HY Qiu Miao-Zhen MZ Wang De-Shen DS Wang Feng-Hua FH Xu Mingyan M Li Yu-Hong YH Xu Rui-Hua RH

Gut 20210906 7

<h4>Objective</h4>Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown.<h4>Design</h4>We conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tum ...[more]

PMID: 34489309

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Project description:BackgroundSurgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC.Patients and methodsPatients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy.ResultsFifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively.ConclusionsPatients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible.Trial registrationClinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

Dataset Information

Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment.

Objective

Design

Results

Conclusion

Publications

Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment.

Similar Datasets

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