Contour variation is a primary source of error when delivering post prostatectomy radiotherapy: Results of the Trans-Tasman Radiation Oncology Group 08.03 Radiotherapy Adjuvant Versus Early Salvage (RAVES) benchmarking exercise.

INTRODUCTION: Variation in target volume delineation from clinical trial protocols has been shown to contribute to poorer patient outcomes. A clinical trial quality assurance framework can support compliance with trial protocol. Results of the TROG 08.03 RAVES benchmarking exercise considering variation from protocol, inter-observer variability and impact on dosimetry are reported in this paper. METHODS: Clinicians were required to contour and plan a benchmarking case according to trial protocol. Geometric pjmirometers including volume, Hausdorff Distance, Mean Distance to Agreement and DICE similarity coefficient were analysed for targets and organs at risk. Submitted volumes were compared to a STAPLE and consensus 'reference' volume for each structure. Dosimetric analysis was performed using dose volume histogram data. RESULTS: Benchmarking exercise submissions were received from 96 clinicians. In total 205 protocol variations were identified. The most common variation was inadequate contouring of the CTV in 84/205 (41%). The CTV volume ranged from 65.3 to 193.1 cm3 with a median of 113.2 cm3 . The most common dosimetric protocol variation related to rectal dosimetry. The mean submitted rectal volume receiving 40 Gy and 60 Gy, respectively, was 56.14% ± 5.55% and 30.25% ± 6.15%. When corrected to the protocol defined length the mean rectal volume receiving 40 Gy was 60.8% ± 7.92%, while the volume receiving 60 Gy was 33.86% ± 8.21%. CONCLUSION: Variations from protocol were found in the RAVES benchmarking exercise, most notably in CTV and rectum delineation. Inter-observer variability was evident. Incorrect delineation of the rectum impacted on dosimetric compliance with protocol.

Optimizing Radiation Therapy Quality Assurance in Clinical Trials: A TROG 08.03 RAVES Substudy.

PURPOSE: To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. METHODS AND MATERIALS: RAVES (Radiation Therapy-Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol required remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. RESULTS: Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P=.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P=.02) and site level (OR 0.72, P=.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P=.05). CONCLUSION: Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation and clinician experience.