What is the role of a molecular tumour (tumor) board in radiation oncology?

Role of Molecular Tumour Boards in Radiation Oncology

Molecular tumour boards (MTBs) serve as critical multidisciplinary platforms that integrate genomic profiling into precision oncology, providing systematic interpretation of complex molecular data to guide treatment decisions, including radiation therapy strategies, particularly for patients with rare cancers, limited treatment options, or complex genomic alterations. 1

Primary Functions of MTBs

MTBs provide genomic-informed clinical recommendations through comprehensive biomarker assessments, with the goal of delivering clinically meaningful treatment strategies that can impact morbidity, mortality, and quality of life 1. The core responsibilities include:

• Systematic interpretation of genomic profiling results to translate complex molecular data into actionable clinical recommendations 1
• Treatment strategy development that may influence choices between different therapeutic modalities, including radiation therapy approaches, or facilitate clinical trial enrollment 1
• Educational support for clinicians navigating the evolving landscape of precision oncology 1
• Germline variant interpretation when tumor-detected alterations suggest hereditary implications 1
• Optimization of diagnostic tool utilization to ensure appropriate molecular testing strategies 1

Multidisciplinary Composition

MTBs must encompass interdisciplinary expertise with key roles for oncologists with genomic expertise, pathologists with molecular training, and clinical geneticists to effectively interpret complex genomic data 1. This multidisciplinary approach has been consistently shown to improve clinical outcomes for cancer patients 1.

Patient Selection Criteria for MTB Discussion

MTBs should prioritize cases where interdisciplinary discussion offers the highest potential benefit 1:

High-Priority Cases

• Complex genomic alterations: Cases with concurrent actionable mutations requiring therapy prioritization, or putative resistance biomarkers without established clinical roles 1
• Rare cancers and limited treatment options: ESMO specifically recommends genomic profiling for all advanced rare cancers, where MTB discussion can identify alternative treatment approaches and facilitate clinical trial access 1
• Unexpected genomic findings: Alterations that may yield novel diagnostic information or challenge initial tumor classification 1
• Discordant testing results: Cases with technical or analytical challenges requiring expert interpretation 1

Impact on Treatment Decisions

Cases should be selected based on potential impact on treatment decisions, including situations where genomic findings may influence radiation therapy planning, choice between treatment modalities, or design of personalized multimodality strategies 1

Clinical Outcomes and Quality Benchmarks

Approximately 30% of patients achieve significant clinical benefit from molecular-matched treatment recommendations, particularly when supported by higher degrees of clinical evidence 1. The ESMO Precision Oncology Working Group established quality benchmarks for MTB effectiveness 1:

Treatment Implementation Benchmarks

• Minimum benchmark: At least 10% of patients with MTB-endorsed recommendations receive MTB-guided therapy 1
• Recommended benchmark: At least 25% receiving MTB-guided therapy 1
• Optimal benchmark: At least 33% receiving MTB-guided therapy 1

These benchmarks reflect the feasibility of MTB recommendations and account for real-world barriers including clinical trial eligibility, drug access, and insurance coverage 1.

Integration into Precision Oncology Programs

MTBs function as integral components of comprehensive precision oncology programs, extending beyond case discussions to encompass patient care coordination, clinical trial access, biomarker-driven treatment harmonization, and real-world evidence generation 1. They facilitate:

• Clinical trial enrollment: Matching patients to appropriate investigational therapies based on molecular profiles 1
• Data standardization: Contributing to registries and real-world evidence collection 1
• Peer-to-peer education: Continuous refinement of precision oncology workflows through structured follow-up 1
• Interdisciplinary collaboration: Breaking down silos between medical oncology, radiation oncology, pathology, and genetics 1

Documentation and Follow-up

MTB recommendations must be documented in structured reports that include genomic-informed treatment strategies, management plans for potential germline alterations, and guidance for additional testing 1. Structured follow-up processes should monitor clinical effectiveness of recommendations to continuously improve MTB performance 1.

Common Pitfalls and Considerations

Resource Allocation Challenges

In resource-limited settings, MTBs must carefully select cases where potential benefits align with availability and affordability of diagnostic and therapeutic resources 1. The most common barriers to implementing MTB recommendations include clinical trial ineligibility, inability to access targeted agents, and insurance coverage limitations 2.

Complexity of Molecular Profiles

No two patients typically have identical molecular aberration patterns - in one series, 107 distinct abnormalities were seen only once among 34 patients, with a median of 4 molecular abnormalities per patient 2. This underscores the necessity of expert multidisciplinary interpretation rather than algorithmic approaches.

Adherence and Implementation

When MTB recommendations are followed, clinical outcomes are favorable - adherence rates of 58-81% have been reported, with objective response rates of 67% and median progression-free survival of 6.3 months in patients receiving recommended targeted therapies 3, 4. However, only 39-61% of cases may warrant a change in clinical management based on molecular findings 3.

Practical Implementation for Radiation Oncology

For radiation oncologists specifically, MTB participation provides:

• Molecular context for radiation planning: Understanding driver mutations and resistance mechanisms that may influence radiation dose, fractionation, or combination strategies
• Patient selection for clinical trials: Identifying candidates for trials combining radiation with molecularly targeted agents
• Prognostic information: Molecular profiles that may inform radiation treatment intensity and follow-up strategies
• Educational value: Staying current with evolving biomarker landscape relevant to radiation oncology practice 1

The heterogeneity in MTB structure globally means recommendations should be adapted to institutional requirements, available resources, and the surrounding healthcare system 1.