Kevin Albuquerque

The role for vaginal cuff brachytherapy boost after external beam radiation therapy in endometrial cancer

To evaluate the role and technique of a vaginal cuff brachytherapy (VB) boost to adjuvant external beam (EB) radiation for endometrial cancer through a systematic review. Relevant trials were identified through a systematic search of the literature. A total of 21 prospective and retrospective studies which had a patient cohort undergoing EB + VB was identified to evaluate for rates of vaginal and pelvic recurrences, overall survival, and toxicity. Additional database studies were utilized to demonstrate differences in local control and overall survival between EB and EB + VB. While there is limited prospective evidence to guide the use of a VB boost after EB, the evidence suggests that patients with a higher risk of a vaginal recurrence such as those with cervical stromal involvement in select Stage III patients may derive local control and survival benefits from a VB boost. Additional individual risk factors such as grade, histology, extent of invasion, margin status, age, and the use of lower doses of EB should be considered when deciding when to add a VB boost.

Predicting which patients may benefit from the hybrid intracavitary+interstitial needle (IC/IS) applicator for advanced cervical cancer: A dosimetric comparison and toxicity benefit analysis

The purpose of this study is to compare the predicted rate of local control and bladder and rectum toxicity rates for image-guided adaptive brachytherapy plans using a tandem and ovoid (T/O) applicator versus using a simulated hybrid intracavitary/interstitial tandem and ring applicator with needles (T/R + N) for patients with locally advanced cervical cancer (LACC). Patients with ≥ FIGO Stage IIB locally advanced cervical cancer treated with T/O from a single institution were included. Simulated treatment plans were created with a T/R + N applicator for the best high-risk clinical target volume (CTV) coverage and minimal dose to organs at risk. Three-year local control rate was estimated using published dose-volume effect relationships. Next, the high-risk CTV EQD2 D90 of T/R + N plans were calculated, and bladder and rectum toxicity rates were estimated. Analysis was performed in subpatient groups defined based on tumor volume and ratio of maximal and minimal tumor radii (RR) that reflects tumor shape asymmetry. Improvements in predicted local control rate for the T/R + N were 0.8, 4.1, 1.6, and 3.9% for groups with tumor volume <35 cc, ≥35 cc, RR < 2.0, and ≥2.0, respectively, with the latter three being statistically significant. Predicted reductions in Grade 2-4 toxicity rates of bladder and rectum were significant in all groups except bladder toxicity in tumor volume <35 cc, when T/R + N plans were normalized to the same CTV coverage as the T/O plans. Comparing unnormalized T/R + N plans and T/O plans, predicted toxicity reductions were significant in all groups except rectum toxicity in RR ≥ 2.0. Predicted reduction of toxicity rate was larger for patients with large tumor or large tumor RR, although some reductions were relatively small. Cases with large tumor (volume ≥35 cc) or large tumor asymmetry (RR ≥ 2.0) would probably benefit more from the use of hybrid applicators.

Updating and Optimizing Anatomic Atlases for Elective Radiation of Para-Aortic Lymph Nodes in Cervical Cancer

Previous studies have proposed 2 different contouring guidelines for the prophylactic radiation of para-aortic lymph nodes (PANs) for locally advanced cervical cancer. Because PAN-mapping atlases in current literature are limited to small patient samples and nodal populations, we updated the PAN atlas with a large data set of positron emission tomography (PET)-positive PANs on PET/computed tomography (CT) from patients with cervical cancer. We identified 176 PET-positive PANs on pretreatment PET/CT of 47 patients with diagnosed International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer. PANs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). PAN clinical target volume (CTV) contours were drawn for all patients based on previously published guidelines by Takiar (CTV-T) and Keenan (CTV-K) and nodal volumetric coverage was assessed. We identified 94 LPA nodes (54%), 71 AC nodes (40%), and 11 (6%) RPC nodes. CTV-T had improved nodal center coverage of 97.6% compared with 85.0% for CTV-K (P < .001). Nodal center coverage for CTV-K and CTV-T (with corresponding PAN) were 79 (84.0%) and 93 (99.0%) LPA nodes (P = .001), 64 (90.1%) and 68 (95.8%) AC nodes (P = .221), and 5 (45.5%) and 9 (81.8%) RPC nodes (P = .134), respectively. Additionally, our updated PAN atlas identified nodal centers anterior to the aorta and inferior vena cava that are not covered by CTV-T but covered by CTV-K due to the 10 mm anterior aortic expansion of CTV-K. We have updated the PAN anatomic map of 176 PET-positive nodes from 47 patients and demonstrated that CTV-T has significantly better PAN coverage over CTV-K for posterior LPA and retrocaval regions for our data set. Additionally, we suggest a modification that includes a blend of CTV-T and CTV-K to provide optimal coverage for the mapped nodes anterior to the great vessels in our data set.

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.

Change in image-guided planning strategies over time impacts oncologic and survival outcomes for intracavitary cervical cancer brachytherapy

Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional nonvolumetric (NV) dosimetry system to three-dimensional computed tomography (CT) and/or magnetic resonance imaging (MRI)-based planning techniques. The purpose of this study is to retrospectively evaluate the relative improvements in image-guided planning strategies over time with regards to dosimetry, survival, and toxicity. A single site retrospective review of 95 locally advanced cervical cancer patients treated with concurrent chemoradiation and high dose rate BT from 2009 to 2016 were divided into three BT planning groups: point-A based NV dosimetry using CT imaging (n = 37), CT-based volumetric dosimetry (n = 33), and MRI-based volumetric dosimetry (n = 25). Overall survival (OS), progression free survival (PFS), and pelvic control (PC) at 5 years were plotted using Kaplan-Meier curves. Univariate and multivariate (MVA) cox proportional-hazards models calculated hazard-ratios (HZ). Finally, acute and late grade 3-4 toxicities were compared between the cohorts. Both MRI and CT had significantly less D2cc to bowel (p < 0.001) and sigmoid (p < 0.001) compared to NV-based planning. On MVA, age (<60 vs. ≥60 years) was significant for worse 5-year OS (HZ: 2.48) and PC (HZ: 5.25). MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and PC (HZ: 0.16). There was no significant difference in grade ≥3 toxicities between the cohorts. CT and MRI-based 3D planning had significantly less D2cc to bowel and sigmoid. MRI-based planning had significant improvement in 5-year OS, PFS, and LC compared to NV on MVA.

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening—a prospective vaginal length and dose correlation

Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

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.