Karen S. Nkiwane

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run

PURPOSE Upfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS EMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1-10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. RESULTS Overall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. CONCLUSION The comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers.

Dose to the non-involved uterine corpus with MRI guided brachytherapy in locally advanced cervical cancer

BACKGROUND AND PURPOSE This study evaluates the impact of MRI guided adaptive brachytherapy (BT) on uterine corpus dose. MATERIAL AND METHODS 84 patients with median follow-up of 18 months were analysed. MRI based BT was done according to GEC-ESTRO guidelines. Non-involved uterine corpus at the time of BT was contoured and the uterine corpus dose (D90 and D98) was evaluated for (1) standard loading pattern with source loading to the tip of the tandem and (2) optimised dose plan. Tandem lengths and heights of the 85 Gy isodose were recorded. RESULTS Dose optimisation resulted in a reduction of active tandem length of 0.4±0.4 cm leading to lowering the D90 to the non-involved uterine corpus from 63.8±9.5 Gy to 56.7±7.5 Gy EQD2 (p<0.0001). Mean active tandem length was 5.0±1.0 cm, and the height of the 85 Gy isodose was 5.7±1.0 cm in optimised plans. CONCLUSIONS MRI guided dose optimisation lowered the dose to the uterine corpus. However, a total EBRT+BT dose larger than 50 Gy was obtained in 99% of patients. Assuming that 45-50 Gy is sufficient to eradicate microscopic disease, the lowering of uterus corpus dose is not expected to induce additional uterine corpus recurrences in the setting of MRI guided adaptive BT. This hypothesis should be tested in a larger number of patients as e.g. the EMBRACE study.

Use of bladder dose points for assessment of the spatial dose distribution in the posterior bladder wall in cervical cancer brachytherapy and the impact of applicator position

PURPOSE To validate the feasibility and use of dose points to characterize the bladder wall dose distribution and investigate potential impact of the applicator position in cervical cancer brachytherapy. METHODS AND MATERIALS One hundred twenty-eight optimized MRI plans were evaluated. The International Commission of Radiation Units and Measurements (ICRU-38) point doses (B(ICRU)), surrogate for bladder base doses, were compared with D(2cc). Vaginal source to superior-anterior border of the symphysis distances were measured and compared within two groups, namely Group 1-B(ICRU)/D(2cc) ≥1 and Group 2-B(ICRU)/D(2cc) <1. Additionally, points at 1.5 and 2 cm cranial to the B(ICRU), parallel to the tandem and the body axis were analyzed. RESULTS Thirty-seven percent of the patients had the ratio B(ICRU)/D(2cc) of 1 or higher, with the 2cc subvolume at the bladder base (Group 1). In 63%, BICRU/D2cc ratio was lower than 1 and the 2cc, cranial to the bladder base (Group 2). Median vaginal source-to-superior-anterior border of the symphysis line distance was -2 cm (range, -3.7 to +1.2 cm) in Group 1 and +1.8 cm (range, -2 to +4.8 cm) in Group 2 (+ cranial/- caudal direction). There was a high correlation between vaginal sources near the symphysis and the 2cc subvolume at the bladder base. The additional points provided no added value. CONCLUSIONS Location of the 2cc subvolume varies in cervical cancer brachytherapy. Maximum doses are at the bladder base if vaginal sources are also in the vicinity of the bladder base indicated by B(ICRU)/D(2cc) ratio of 1 or higher. Such variation should be considered in dose-effect analyses and intercomparisons, as the same D(2cc) at different bladder locations may correlate with different morbidity profiles and severity Reporting D(2cc) and B(ICRU) doses together therefore remains essential.

Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy

PURPOSE To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients. MATERIALS AND METHODS 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/β 10 Gy and 3 Gy. RESULTS Median V85 Gy, V75 Gy and V60 Gy EQD210 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD210 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm3), intermediate (25-35 cm3) and large (>35 cm3) CTVHR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A. CONCLUSIONS MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTVHR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT.