Long-term data from the NRG-RTOG 0617 trial dampened the idea of intensified locoregional radiotherapy (RT) in patients with stage III non-small cell lung cancer (NSCLC), as that group had significantly worse survival with dose-escalated RT, potentially related to increased toxicity from higher irradiation of the heart and lung. Consequently, researchers explored individualized/adaptive dose-intensified RT in patients with local tumor progression and/or recurrence.
The phase II NRG-RTOG1106/ECOG-ACRIN 6697 trial (NCT01507428) tested whether mid-treatment FDG-PET/CT could guide individualized/adaptive dose-intensified RT with the aim of improving and predicting outcomes. The study, published in the Journal of Clinical Oncology, revealed that while the adaptive approach was feasible and safe, it did not significantly improve efficacy outcomes.
Study Details and Findings
The trial randomized patients to either standard RT (60 Gy/30 fractions) or FDG-PET–guided adaptive treatment, stratified by substage, primary tumor size, and histology. Patients in the adaptive arm received an individualized, intensified boost RT dose to residual metabolically active areas, resulting in a mean RT dose of 71 Gy in 30 fractions and a mean lung dose of 17.9 Gy.
The primary therapeutic endpoint was 2-year centrally reviewed freedom from local-regional progression (FFLP). The results showed no significant difference in centrally reviewed 2-year FFLP between the standard (59.5%) and adaptive arms (54.6%; P=0.66). There were also no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P>0.4).
Implications and Future Directions
The authors concluded that midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes. They hypothesize that radiation dose selection needs even greater individualization, on the basis of intrinsic radiosensitivity defined in each patient, and that RT planning should consider the risks of cumulative irradiation of circulating lymphocytes. Greater attention to radiation dose to the heart and great vessels is needed in future studies.
Jonathan P.S. Knisely, MD, a radiation oncologist at Weill Cornell Medicine, suggested that the findings provide promise for patients so treated to further benefit from post-treatment immunotherapy with durvalumab (Imfinzi).
Diversity in Clinical Trials
Notably, the study had a relatively high percentage of Black enrollees (approximately 12%), addressing the underrepresentation of minority populations in clinical trials. Researchers emphasized the importance of addressing spiritual beliefs and logistical factors that influence the decision-making process of Black patients regarding clinical trial participation.
