Image Guided Brachytherapy Quality Assurance on NRG GY017, an NRG Oncology Clinical Trial Investigating the Sequencing of Immunotherapy and Chemoradiation for Locally Advanced Cervical Cancer

Purpose/Objective(s)

NRG GY-017 is a randomized Phase I trial of the anti-PD-L1 antibody atezolizumab administered neoadjuvantly and concurrently (Arm A) or concurrently with chemo RT (Arm B) in patients with node positive locally advanced cervical cancer, with 3 total cycles on each arm. All subjects were treated with PALN extended field external beam radiation therapy (EBRT) and brachytherapy (BT) boost. This trial is a pharmacodynamics study, 3D image-based BT was strongly recommended, and a quality assurance workflow was specified in the protocol. Herein, we report the BT dosimetry results from the NRG GY-017 trial and practice patterns from the participating centers in this trial.

Materials/Methods

All patients were to be treated with 3D image based HDR or PDR BT following EBRT either with point or volume directed plans. The 2D LDR BT was also allowed. CT or MR images were used to delineate the target volume. MRI based target delineation was recommended for identifying the GTV. The MRI could be reused by superimposition for CT based planning, if only CT images for subsequent fractions are used with the applicator in place. Each participating center was to submit brachytherapy plans via TRIAD after the BT course was complete. The clinical trial QA center compiled the BT fractions for each trial patient using the trial specific dosimetry evaluation template. The expert physician scored the contours and plans as per protocol, variation acceptable or major deviation.

Results

Forty patients were enrolled from 9 institutions among designated “safety lead-in” participating centers for this trial in the United States. But 32 patients from 7 institutions had evaluable BT dosimetry results. Twenty-one BT submissions (66%) were completed during the trial period and the rest of the data were submitted after the trial was closed. For the applicator use, 19 patients (59%) had intracavitary only, and 13 (41%) patients had supplemental interstitial (hybrid) or interstitial applications. Point dose directed planning was performed for 4 patients and 28 patients had volume directed plans (n = 28; 87.5%). For imaging use, 2 patients had MRI plans submitted, and the rest of the patients had CT planning. 31 patients had HDR BT with 27.5 Gy-30 Gy in either 4 or 5 fractions, while 1 patient had LDR BT. For the dose constraints compliance per protocol, there were 7 patients with 9 events scored as major deviations (22%), 7 events exceeding critical organ dose limits and 2 events deviating from the target dose.

Conclusion

Brachytherapy on this trial showed a wide range of practice patterns and suggest that BT trial-specific quality assurance review and standardized data submission processes may have the potential to enhance quality and safety for clinical trials. This report presents the first modern GYN BT trial dosimetry results, guiding future GYN BT trial data collection and quality assurance processes.