Allen Yen

Spare the Bowel, Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix

The standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage. A retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART. The average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage. Based on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.

Optimizing Online Adaptation Timing in the Treatment of Locally Advanced Cervical Cancer

Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared. A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test. Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART. This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume.

Progression-Free Survival Prediction for Locally Advanced Cervical Cancer After Chemoradiotherapy With MRI-based Radiomics

A significant proportion of locally advanced cervical cancer (LACC) patients experience disease progression post chemoradiotherapy (CRT). Currently existing clinical variables are suboptimal predictors of treatment response. This study reported a radiomics-based model leveraging information extracted from magnetic resonance (MR) T2-weighted image (T2WI) to predict the progression-free survival (PFS) for LACC following CRT. Radiomics features were extracted from pre-treatment MR T2WI in 105 LACC patients. Following pre-feature selection and a step forward feature selection method, an optimal feature set was determined with a Cox proportional hazard (CPH) model. The PFS predictions were generated through a radiomics-clinical combined model utilized five repeated nested 5-fold cross-validation (5-fold CV). Disease progression risk was stratified into high- and low-risk groups based on the predicted PFS and assessed by Kaplan-Meier analysis. The radiomics texture feature extracted from MR T2WI significantly predict PFS in LACC after CRT. In comparison with the model using clinical variables alone, the radiomics-clinical combined model achieves significantly improved performance in testing patient cohort, achieving higher C-index (0.748 vs 0.655) and area under the curve (0.798 vs 0.660 for 2-year PFS). Meanwhile, the proposed method significantly differentiated the high- and low-risk patients groups for disease progression (P < 0.001). An MR T2WI-based radiomics and clinical combined model provided improved prognostic capabilities in predicting the PFS for LACC patients treated with CRT, outperforming a model using clinical variables alone. The incorporation of MR T2WI-based radiomics is promising in assisting in personalized management in LACC, indicating the potential of MR T2WI radiomics as imaging biomarker.

Online Adaptive Radiotherapy Cervical Cancer With Reduced Margin for Cervical Cancer

Online adaptive radiotherapy (oART) has demonstrated to be feasible to reduce planning target volume (PTV) margins for cervical cancer. To explore the value of reduced margins in oART for cervical cancer, we conducted a prospective clinical trial to determine the clinical efficacy and toxicity of reduced margins.