Objective:

To outline the evolution and impact of RTOG/NRG trials on clinical standards for CNS tumors.

Approach:

• Foundational era: Established radiotherapy dose, fractionation, and feasibility for gliomas through early investigations.
• Methodological maturation: Developed prognostic stratification and efficient phase II trials to address limitations of radiotherapy intensification.

Key Findings:

• RTOG/NRG trials have significantly influenced evidence-based care for CNS tumors, particularly through the validation of molecular stratification.
• Long-term follow-up from RTOG 94-02 demonstrated that incorporating PCV into radiotherapy doubled survival among patients with 1p19q co-deleted, IDH mutant high-grade gliomas.
• The integration of patient-reported outcomes and cognitive function assessments has become standard in CNS trials.
• Collaborative efforts with other NCTN groups have accelerated trial accrual and evidence generation, enhancing the robustness of findings.

Interpretation:

The trials have evolved to address the complexities of CNS tumors, integrating advanced methodologies and collaborative frameworks as demonstrated through various studies.

Limitations:

• Generalizability of findings may be constrained due to the unique challenges posed by CNS tumors, including biological heterogeneity and infiltrative growth.
• Single-institution studies may not capture the full spectrum of treatment responses, limiting the applicability of findings.

Conclusion:

RTOG/NRG trials have established a robust framework for the treatment of CNS tumors, emphasizing the importance of multi-institutional collaboration and methodological advancements in trial design. Compliance with regulatory standards and ethical considerations has been prioritized throughout the trial processes to ensure the integrity and applicability of findings.