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Tumor mutational burden in colorectal cancer: Implications for treatment
Adriana Marques1, Patrícia Cavaco2, Carla Torre1
1Research Institute for Medicines (iMed.ULisboa), Lisboa 1649-003, Portugal; Faculdade de Farmácia, Universidade de Lisboa, Lisboa 1649-003, Portugal.
Abstract:
Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice. Here, we compiled 45 colorectal cancer studies utilizing numerical thresholds for high-TMB. In this group of studies, TMB cut-offs ranged from 6.88 to 41 mut/Mb and were most often set at 10, 17, or 20 mut/Mb. Additionally, we observed divergent TMB definitions and inconsistent disclosure of specific methodological details, which collectively emphasize the substantial lack of harmonization within the field. Ongoing efforts to harmonize TMB assessment will be critical to validate TMB as a predictive marker of immunotherapy response.
Insights
Tumor mutational burden (TMB) shows promise for predicting immunotherapy response in colorectal cancer. However, inconsistent assessment methods across studies hinder its clinical use, necessitating harmonization efforts for reliable biomarker validation.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint inhibitors have transformed advanced solid cancer treatment.
- Their benefit in colorectal cancer is currently restricted to patients with deficient mismatch repair or high microsatellite instability.
- Tumor mutational burden (TMB) is a potential biomarker for predicting immunotherapy response.
Purpose of the Study:
- To analyze numerical thresholds for high TMB across 45 colorectal cancer studies.
- To identify variations in TMB definitions and reporting methodologies.
- To highlight the lack of standardization in TMB assessment.
Main Methods:
- Compilation of 45 colorectal cancer studies that used numerical thresholds for high TMB.
- Analysis of reported TMB cut-offs and definitions.
- Assessment of methodological detail consistency.
Main Results:
- TMB cut-offs in the analyzed studies ranged from 6.88 to 41 mutations per megabase (mut/Mb).
- Commonly used TMB cut-offs were 10, 17, or 20 mut/Mb.
- Significant divergence in TMB definitions and inconsistent reporting of methodological details were observed.
Conclusions:
- The current lack of harmonization in TMB assessment and reporting impedes its routine clinical application.
- Standardization of TMB evaluation is crucial for its validation as a predictive biomarker for immunotherapy response in colorectal cancer.
- Ongoing efforts to harmonize TMB assessment are critical for advancing precision oncology.
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