Radiation Therapy Quality Assurance (RTQA) of Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer in the PROCLAIM Phase 3 Trial.

PURPOSE: Chemoradiation therapy trials of different tumors, including lung cancer, have shown a correlation between protocol deviations and adverse outcomes. Radiation therapy quality assurance (RTQA) was mandated for all patients treated in the PROCLAIM trial evaluating 2 different chemoradiation therapy regimens. The RTQA results were evaluated from the PROCLAIM study, and the impact of irradiation deviations on efficacy outcomes was investigated. METHODS AND MATERIALS: The study was conducted from 2008 to 2014. Review of the irradiation plan was mandated for all patients. Real-time review was performed prior to irradiation start for the first enrolled patient at each site and randomly in 20% of additional patients, with non-real-time review in the remainder. The RTQA criteria evaluated included planning target volume coverage, dose homogeneity, volume of lung receiving ≥20 Gy, and maximum point dose to spinal cord. RESULTS: Major RTQA violations occurred in 40 of 554 patients, treated at 28 sites. Seven sites treated ≥2 patients with major violations. Stage IIIB disease and larger planning target volume were observed more frequently in patients with major violations. Major violations were more prevalent in sites treating either <6 patients or >15 patients. Patients treated at sites enrolling ≥2 patients with major violations (n = 86) had lower median overall survival (21.1 months vs 29.8 months; hazard ratio, 1.442) and progression-free survival (7.3 months vs 11.3 months; hazard ratio, 1.345) than patients treated at sites without major violations. These findings remained significant for overall survival on multivariate analysis. CONCLUSIONS: Major violations in treatment plans were uncommon in the PROCLAIM study, possibly reflecting mandatory RTQA. The RTQA violations were more frequent in patients requiring more complex chemoradiation therapy plans. Poorer observed outcomes at centers with multiple major violations are hypothesis generating.

PROCLAIM: A phase III study of pemetrexed, cisplatin, and radiation therapy followed by consolidation pemetrexed versus etoposide, cisplatin, and radiation therapy followed by consolidation cytotoxic chemotherapy of choice in locally advanced stage III non-small-cell lung cancer of other than predominantly squamous cell histology.

This clinical trial summary provides the background and rationale for a randomized trial examining the benefits of pemetrexed/ cisplatin chemotherapy combined with radiation followed by consolidation pemetrexed in patients with unresectable stage IIIA/B non-small-cell lung cancer. The rationale for the selection of the control arm is provided, and study design limitations are discussed. The primary outcome is survival, and secondary outcomes include progression-free survival, toxicities, and 1-, 2-, and 3-year survival rates. Radiation quality control is a key component of the trial.