OA24.01 Radiotherapy Quality Assurance of Concurrent Chemoradiotherapy in PROCLAIM Phase III Trial

Trials of chemoradiotherapy for different tumors, including lung cancer, have shown a correlation between protocol deviations and adverse outcomes. Radiation quality assurance (RTQA) was mandated for all patients treated in the PROCLAIM (NCT00686959) trial evaluating two different chemoradiotherapy regimens. The study was open to accrual between 2008-2012. Planned chemoradiotherapy dose was 60-66 Gy in daily 2 Gy fractions. Quality was assessed through review of radiation treatment plans and monitoring of protocol violations. Review of the radiation plan was mandated for all patients; prior to radiation start for the first enrolled patient at each site. Real-time review was performed randomly in 20% of additional patients with nonreal-time review performed for the remainder. Parameters assessed for major violations per protocol included: <95% of planned total volume (PTV) received by 93% of prescribed dose; >1 cm3 contiguous volume within or outside the PTV received >115% of prescribed dose; V20 (volume of lung receiving ≥20 Gy) >38%; and maximum point dose to spinal cord of >48 Gy. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kapan-Meier methodology and groups were compared by log-rank test and Cox proportional hazard modeling. Of 598 patients randomized in 126 investigational sites, 554 received study assigned chemoradiotherapy. The median dose delivered was 66 Gy, with 92.6% of patients receiving planned chemoradiotherapy dose (60-66 Gy). A total of 40 patients, enrolled at twenty-eight sites had major RTQA violations. Seven sites enrolled ≥2 patients with major violations. Patients with major violations has a higher incidence of Stage IIIB disease (70.0% vs. 50.6%) and larger tumors (median planned PTV=653 vs. 523cc) than patients with no violations. Patients treated at sites with ≥2 patients with violations (n=86), had a lower median OS (median 21.1 vs. 29.8 months; HR 1.442) and median PFS (median 7.3 vs. 11.3 months; HR 1.345) than patients at sites where none had violations. Major chemoradiotherapy protocol violations were uncommon in the PROCLAIM study, which may be a reflection of the mandatory RTQA. Protocol violations were more frequent in patients with Stage IIIB and larger tumors, which generally require more complex chemoradiotherapy plans. The observation of discrepant outcomes at centers with multiple major RTQA violations is hypothesis-generating but should be interpreted with caution due to the small number of patients.