Importance of training in external beam treatment planning for locally advanced cervix cancer: Report from the EMBRACE II dummy run.

BACKGROUND AND PURPOSE: The EMBRACE II study combines state-of-the-art Image-Guided Adaptive Brachytherapy in cervix cancer with an advanced protocol for external beam radiotherapy (EBRT) which specifies target volume selection, contouring and treatment planning. In EMBRACE II, well-defined EBRT is an integral part of the overall treatment strategy with the primary aim of improving nodal control and reducing morbidity. The EMBRACE II EBRT planning concept is based on improved conformality through relaxed coverage criteria for all target volumes. For boosting of lymph nodes, a simultaneous integrated boost and coverage probability planning is applied. Before entering EMBRACE II, institutes had to go through accreditation. MATERIAL AND METHODS: As part of accreditation, a treatment planning dummy-run included educational blocks and submission of an examination case provided by the study coordinators. Seventy-one centers submitted 123 EBRT dose distributions. Replanning was required if hard constraints were violated or planning concepts were not fully accomplished. Dosimetric parameters of original and revised plans were compared. RESULTS: Only 11 plans violated hard constraints. Twenty-seven centers passed after first submission. 27 needed one and 13 centers needed more revisions. The most common reasons for revisions were low conformality, relatively high OAR doses or insufficient lymph node coverage reduction. Individual feedback on planning concepts improved plan quality considerably, resulting in a median body V43Gy reduction of 158 cm3 from first plan submission to approved plan. CONCLUSION: A dummy-run as applied in EMBRACE II, consisting of training and examination cases enabled us to test institutes' treatment planning capabilities, and improve plan quality.

Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II.

PURPOSE: To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT). METHODS AND MATERIALS: EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared. RESULTS: For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively. CONCLUSIONS: Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency.

Cone beam computed tomography-based monitoring and management of target and organ motion during external beam radiotherapy in cervical cancer.

BACKGROUND AND PURPOSE: Organ motion is a challenge during high-precision external beam radiotherapy in cervical cancer, and improved strategies for treatment adaptation and monitoring of target dose coverage are needed. This study evaluates a cone beam computed tomography (CBCT)-based approach. MATERIALS AND METHODS: In twenty-three patients, individualized internal target volumes (ITVs) were generated from pre-treatment MRI and CT scans with full and empty bladders. The target volumes encompassed high-risk clinical target volume (CTV-T HR) (gross tumor volume + remaining cervix) and low risk (LR) CTV-T (CTV-T HR + uterus + parametriae + upper vagina). Volumetric Modulated Arc Therapy (VMAT) was used to deliver a dose of 45 Gy in 25 fractions. CBCTs were used for setup and for radiation therapists (RTTs) to evaluate the target coverage (inside/outside the planning target volume). CBCTs were reviewed offline. Estimates of the dose delivered with minimum (point) doses across all fractions to CTV-T HR (aim 42.75 Gy) and CTV-T LR (aim 40 Gy) were assessed. In patients with insufficient dose coverage, re-plans were generated based on previous imaging. RESULTS: Median (range) of the ITV-margins (mean of anterior-posterior margins) related to uterus and cervix was 1.2 (0.5-2.2 and 1.0-2.1) cm. RTTs were able to assess the target coverage in 90% of all CBCTs (505/563). With re-planning, one patient had considerable benefit (12.7 Gy increase of minimum dose) to CTV-T LR_vagina, four patients had improved dose to the CTV-T LR_uterus (1.2-1.8 Gy), and 3 patients did not benefit from re-planning. CONCLUSIONS: Daily CBCT-based monitoring of target coverage by the RTTs has proven safe with limited workload. It allows for reduction in the treated volumes without compromising the target dose coverage.