Image-based longitudinal assessment of external beam radiation therapy for gynecological malignancies
This thesis consists of two studies. Study 1 is an assessment of dose-volume metrics of an 18F-FDG PET adaptive radiation therapy for vulvar and cervical cancer patients.Study 2 is an evaluation of cumulative dose distributions from external beam radiation therapy using CT-to-CBCT deformable image registration (DIR) for cervical cancer patients.
Study 1: Assessment of dose-volume metrics of an 18F-FDG PET adaptive radiation therapy for vulvar and cervical cancer patientsPurpose: Adaptive radiation therapy (ART) enables treatment to be modified with the goal of improving the dose distribution to the patient due to changes in anatomy. Fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) is used for staging, treatment planning, and assessing treatment response, but can also be used to adapt treatment. In an adaptive PET/CT study, an additional PET/CT scan is acquired for planning purposes after a certain prescribed dose has been delivered. The intratreatment PET/CT is used to re-contour the volumes and create a new treatment plan that is used to deliver the remaining dose for the treatment. The goal of adaptive radiation therapy (ART) is to reduce the dose to normal tissues while maintaining the prescribed dose to the adapted PTV. Materials and Methods: In this IRB-approved protocol, patients with vulvar and cervical cancer received a planning PET/CT and an intratreatment PET/CT. Radiation therapy consisted of either intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with 1.8 Gy once daily to a total of 45 to 50.4 Gy and simultaneous integrated boosts (SIB) to involved pelvic or para-aortic (PA) lymph nodes. The primary tumor was treated to 64.4 to 66.4 Gy with sequential boosts for the vulvar cancer patients. Cervical cancer patients were boosted with brachytherapy. SIB dose ranged from a total of 64.4 Gy to 66.4 Gy in 25 fractions determined by the treating physician and organs-at risk (OAR) tolerance. An intratreatment PET/CT was obtained at 12-20 fractions when the delivered dose was between 30 to 36 Gy. All patients were re-planned with revised OAR, gross tumor volume (GTV) and planning target volume (PTV) contours. The same dose goals remained on the adapted plan. Dosimetric metrics for OARs were compared using the Wilcoxon signed rank test. The criteria for determining statistical significance was established as a p-value less than 0.05. Results: In the vulvar analysis, out of 20 eligible patients, ART resulted in significant reductions in OAR doses. For bladder, max dose (Dmax) median reduction (MR) was 1.1 Gy ((IQR 0.48 – 2.3 Gy), p < 0.001) and for D2cc MR was 1.5 Gy ((IQR 0.51 – 2.1 Gy), p < 0.001). For bowel, Dmax MR was 1.0 Gy ((IQR 0.11 – 2.9 Gy), p < 0.001), for D2cc MR was 0.39 Gy ((IQR 0.023 – 1.7 Gy), p < 0.001), and for D15cc MR was 0.19 Gy ((IQR 0.026 – 0.47 Gy), p = 0.002)). For rectum, mean dose (Dmean) MR was 0.66 Gy ((IQR 0.17 – 1.7 Gy) p = 0.006) and for D2cc MR was 0.46 Gy ((IQR 0.17 – 0.80 Gy), p = 0.006). Thirty-seven cervical patients were analyzed. ART resulted in significant reductions in OAR doses. For bladder, max dose (Dmax) median reduction (MR) was 0.89 Gy ((IQR 0.23 – 2.14 Gy), p = 0.001) and for D2cc MR was 0.38 Gy ((IQR 0.12 – 1.36 Gy), p<0.0001). For bowel, Dmax MR was 3.27 Gy ((IQR 0.50 – 5.41 Gy), p < 0.0001). For D2cc MR was 2.09 Gy ((IQR 0.30 – 4.97 Gy), p < 0.0001), and for D15cc MR was 0.57 Gy (IQR 0.22 – 2.07 Gy)). For rectum, Dmean MR was 0.13 Gy ((IQR 0.09 – 0.24 Gy) p = 0.0025), and for D2cc MR was 0.44 Gy ((IQR 0.14 – 1.02 Gy), p < 0.0001). Conclusions: Based on the analysis and response to ART of 20 eligible patients with vulvar cancer and 37 eligible patients with cervical cancer, it can be concluded that ART resulted in a significant reduction in OAR doses, including bladder, bowel, and rectum. Overall, these findings suggest that ART can effectively reduce the radiation dose to OARs and improve treatment outcomes for patients with gynecological cancers.
Study 2: Evaluation of cumulative dose distributions from external beam radiation therapy using CT-to-CBCT deformable image registration (DIR) for cervical cancer patients Purpose: Organ motion during radiation therapy in the pelvic region can potentially lead to uncertainties with the dose delivered to critical organs during fractionated treatment. The purpose of this study is to investigate, by means of using deformable image registration (DIR) and dose summation techniques, the differences between the planning dose and the delivered dose as calculated from the longitudinal cone-beam CT (CBCT) images for cervical cancer patients. Materials and Methods: Cervical cancer patients treated with external beam radiation therapy (EBRT) received a planning CT (pCT) and five CBCTs, once every five fractions of treatment. The “Merged CBCT” feature in MIM Maestro (MIM Software, Cleveland, OH) was performed between the pCT and each CBCT to generate an extended field-of-view (FOV) CBCT (mCBCT). A free-form multi-modality DIR was then performed between the pCT and the mCBCT to deform the pCT structures onto the mCBCT. DIR-generated bladder and rectum contours were further adjusted by a physician, and Dice Similarity Coefficients (DSC) were calculated between the two. After deformation, the investigated doses on the mCBCT were: 1) recalculated in Eclipse TPS (Varian Medical Systems, Palo Alto, CA) using original plan parameters (ecD), and 2) deformed from planning dose (pD) using the deformation matrix (mdD). Dose summation was performed to the first week’s mCBCT. Bladder D2cc, Dmax, Dmean, V45, and D50, rectum D2cc, Dmax, Dmean, and D50, and PTV45 D90 and D98 were compared between the three calculated doses. Dose distributions were compared in terms of dose volume histograms (DVHs) and gamma analysis. The Wilcoxon signed rank test was used to compare dosimetric metrics with statistical significance defined at p < 0.05. Results: For the ten patients analyzed, the average DSC were 0.72 ± 0.15 for bladder and 0.80 ± 0.11 for rectum. For most cases, only the superior and inferior slices were edited by physician. Regardless of the method of dose calculation (ecD or mdD), D2cc (bladder and rectum), and D90 and D98 (PTV45) were within 5% of pD for at least 9 out of 10 patients. For one patient each for bladder, rectum, and PTV45, the agreement was worse than 5%, with the largest difference of 15.3% for bladder D2cc in a patient with large bladder filling differences. For the Eclipse calculated dose on the merged CBCT (ecD) and t;he MIM deformed dose on merged CBCT (mdD), the bladder Dmax was within 5% for 8 out of 10 patients, and rectum Dmax was within 5% for 7 out of 10 patients. All 10 patients for ecD and mdD were >5% for bladder V45 due to the large variations in bladder volume throughout treatment. Statistically significant differences for bladder D2cc between the ecD and the mdD (p = 0.047). For bladder D50, significant differences between pD and ecD (p = 0.009) and ecD and mdD (p = 0.005). Statistically significant differences for rectum D2cc between the pD and ecD (p = 0.028) as well as ecD and mdD (p = 0.005). Statistically significant differences for D98 between the pD and ecD (p = 0.028) and pD and mdD (p = 0.007). The gamma analysis between the ecD and pD matched 90% of the voxels for 3 out of 10 patients and between the mdD and pD for 1 out of 10 patients. Conclusions: In this study, we evaluated cumulative doses based on weekly CBCTs using a commercially-available DIR software. Using DIR and the new Merged CBCT feature, we determined that reporting the initial planning dose would not introduce a more than 5% difference in 90% of cases studied. Our results indicate that the mdD produces similar dose values as the ecD for the OARs and PTV. The proposed workflow should be used on a case-by-case basis when the weekly CBCT shows marked difference in organs-at-risk from the planning CT.
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