Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study
Background: Colorectal cancer (CRC) is the third most diagnosed cancer globally and the second leading cause of cancer-related deaths. Despite advancements, metastatic CRC (mCRC) has a five-year survival rate below 20%. Next-generation sequencing (NGS) is recommended nowadays to guide mCRC treatment...
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2025-01-01
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| author | Ricardo Roque Rita Santos Luís Guilherme Santos Rita Coelho Isabel Fernandes Gonçalo Cunha Marta Gonçalves Teresa Fraga Judy Paulo Nuno Bonito |
| author_facet | Ricardo Roque Rita Santos Luís Guilherme Santos Rita Coelho Isabel Fernandes Gonçalo Cunha Marta Gonçalves Teresa Fraga Judy Paulo Nuno Bonito |
| author_sort | Ricardo Roque |
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| description | Background: Colorectal cancer (CRC) is the third most diagnosed cancer globally and the second leading cause of cancer-related deaths. Despite advancements, metastatic CRC (mCRC) has a five-year survival rate below 20%. Next-generation sequencing (NGS) is recommended nowadays to guide mCRC treatment; however, its clinical utility when compared with traditional molecular testing in mCRC is debated due to limited survival improvement and cost-effectiveness concerns. Methods: This retrospective study included mCRC patients (≥18 years) treated at a single oncology centre who underwent NGS during treatment planning. Tumour samples were analysed using either a 52-gene Oncomine™ Focus Assay or a 500+-gene Oncomine™ Comprehensive Assay Plus. Variants were classified by clinical significance (ESMO ESCAT) and potential benefit (ESMO-MCBS and OncoKBTM). The Mann–Whitney and Chi square tests were used to compare characteristics of different groups, with significance at <i>p</i> < 0.05. Results: Eighty-six metastatic colorectal cancer (mCRC) patients were analysed, all being MMR proficient. Most cases (73.3%) underwent sequencing at diagnosis of metastatic disease, using primary tumour samples (74.4%) and a focused NGS assay (75.6%). A total of 206 somatic variants were detected in 86.0% of patients, 31.1% of which were classified as clinically significant, predominantly KRAS mutations (76.6%), with G12D and G12V variants as the most frequent. Among 33.7% RAS/BRAF wild-type patients, 65.5% received anti-EGFR therapies. Eleven patients (12.8%) had other actionable variants which were ESCAT level I-II, including four identified as TMB-high, four KRAS G12C, two BRAF V600E, and one HER2 amplification. Four received therapies classified as OncoKbTM level 1–2 and ESMO-MCBS score 4, leading to disease control in three cases. Conclusions: NGS enables the detection of rare variants, supports personalised treatments, and expands therapeutic options. As new drugs emerge and genomic data integration improves, NGS is poised to enhance real-world mCRC management. |
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| id | doaj-art-635fc10e08274d1c883bceadd1ec098f |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-635fc10e08274d1c883bceadd1ec098f2025-08-20T03:43:36ZengMDPI AGDNA2673-88562025-01-0151410.3390/dna5010004Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort StudyRicardo Roque0Rita Santos1Luís Guilherme Santos2Rita Coelho3Isabel Fernandes4Gonçalo Cunha5Marta Gonçalves6Teresa Fraga7Judy Paulo8Nuno Bonito9Medical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalMedical Oncology Department, Coimbra Portuguese Institute of Oncology, 3000-075 Coimbra, PortugalBackground: Colorectal cancer (CRC) is the third most diagnosed cancer globally and the second leading cause of cancer-related deaths. Despite advancements, metastatic CRC (mCRC) has a five-year survival rate below 20%. Next-generation sequencing (NGS) is recommended nowadays to guide mCRC treatment; however, its clinical utility when compared with traditional molecular testing in mCRC is debated due to limited survival improvement and cost-effectiveness concerns. Methods: This retrospective study included mCRC patients (≥18 years) treated at a single oncology centre who underwent NGS during treatment planning. Tumour samples were analysed using either a 52-gene Oncomine™ Focus Assay or a 500+-gene Oncomine™ Comprehensive Assay Plus. Variants were classified by clinical significance (ESMO ESCAT) and potential benefit (ESMO-MCBS and OncoKBTM). The Mann–Whitney and Chi square tests were used to compare characteristics of different groups, with significance at <i>p</i> < 0.05. Results: Eighty-six metastatic colorectal cancer (mCRC) patients were analysed, all being MMR proficient. Most cases (73.3%) underwent sequencing at diagnosis of metastatic disease, using primary tumour samples (74.4%) and a focused NGS assay (75.6%). A total of 206 somatic variants were detected in 86.0% of patients, 31.1% of which were classified as clinically significant, predominantly KRAS mutations (76.6%), with G12D and G12V variants as the most frequent. Among 33.7% RAS/BRAF wild-type patients, 65.5% received anti-EGFR therapies. Eleven patients (12.8%) had other actionable variants which were ESCAT level I-II, including four identified as TMB-high, four KRAS G12C, two BRAF V600E, and one HER2 amplification. Four received therapies classified as OncoKbTM level 1–2 and ESMO-MCBS score 4, leading to disease control in three cases. Conclusions: NGS enables the detection of rare variants, supports personalised treatments, and expands therapeutic options. As new drugs emerge and genomic data integration improves, NGS is poised to enhance real-world mCRC management.https://www.mdpi.com/2673-8856/5/1/4next-generation sequencingcolorectal canceractionable variantstargeted treatmentsreal-world data |
| spellingShingle | Ricardo Roque Rita Santos Luís Guilherme Santos Rita Coelho Isabel Fernandes Gonçalo Cunha Marta Gonçalves Teresa Fraga Judy Paulo Nuno Bonito Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study DNA next-generation sequencing colorectal cancer actionable variants targeted treatments real-world data |
| title | Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study |
| title_full | Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study |
| title_fullStr | Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study |
| title_full_unstemmed | Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study |
| title_short | Outcomes of Broader Genomic Profiling in Metastatic Colorectal Cancer: A Portuguese Cohort Study |
| title_sort | outcomes of broader genomic profiling in metastatic colorectal cancer a portuguese cohort study |
| topic | next-generation sequencing colorectal cancer actionable variants targeted treatments real-world data |
| url | https://www.mdpi.com/2673-8856/5/1/4 |
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