Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Multi-institutional Development and Validation of Contouring Guidelines for Para-aortic Elective Nodal Irradiation in Prostate Cancer Based on Patterns of Involvement on Targeted Molecular Imaging Positron Emission Tomography/Computed Tomography.

PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.

Validating Modern NRG Oncology Pelvic Nodal and Groupe Francophone de Radiothérapie Urologique Prostate Bed Contouring Guidelines for Post-Prostatectomy Salvage Radiation: A Secondary Analysis of the LOCATE Trial.

PURPOSE: We used the patterns of recurrence on 18F-fluciclovine positron emission tomography (PET)-computed tomography (CT) in patients enrolled in the LOCATE trial after prostatectomy to evaluate how well the most recent NRG Oncology and Groupe Francophone de Radiothérapie Urologique (GFRU) contouring recommendations encompassed all sites of recurrence in the prostate fossa and pelvic nodes in comparison to former Radiation Therapy Oncology Group (RTOG) recommendations. METHODS AND MATERIALS: Patients with biochemically recurrent prostate cancer after radical prostatectomy with a positive finding within the prostate fossa or pelvic nodes on 18F-fluciclovine PET/CTs were identified from the LOCATE patient population. Areas of gross disease were delineated. Prostate fossa contours were delineated using both the 2010 RTOG consensus guidelines and the recently published 2020 GFRU consensus guidelines. Pelvic nodes were contoured with both the 2009 RTOG consensus guidelines and the 2020 NRG consensus guidelines. The performance of the contouring guidelines was assessed by determining what proportion of gross recurrent lesions were encompassed completely or marginally. RESULTS: Of the 213 patients within the LOCATE trial, 45 patients were eligible for analysis with positive 18F-fluciclovine PET findings. Of the 30 total prostate fossa recurrences, the 2010 RTOG contour covered 20 (67%) and missed or marginally covered 10 (33%). The 2020 GFRU contour covered 27 recurrences (90%), and missed or marginally covered 3 (10%). Of the 43 total nodal recurrences, the 2009 RTOG pelvic nodal contour covered 29 nodes (67%), and missed or marginally covered 14 (32%). The 2020 NRG pelvic nodal contour covered 43 nodes (100%), with no misses or marginal coverage. CONCLUSIONS: This secondary analysis of the LOCATE trial exemplifies the improved coverage of the latest prostate fossa contouring recommendations from the GFRU. Similarly, it also validates the updated 2020 NRG pelvic nodal contouring guidelines by demonstrating improved coverage of recurrent disease in this patient population.

Osteoradionecrosis of the skull base.

Radiation therapy (RT) is often necessary for the treatment of head and neck cancers. Osteoradionecrosis (ORN) is a rare, but potentially serious complication of RT. RT leads to the destruction of vasculature in radiated tissue causing hypoxia and tissue necrosis. ORN can occur in any bone, but bones with naturally poor blood supply appear to be more susceptible. Bones of the skull base are susceptible, with ORN occurring in the anterior, central, and lateral skull base. Risk factors include cancer type and location, radiation dose, and a variety of patient factors. Patients often present with pain, bleeding, and foul odor and are typically found to have exposed and necrotic bone. Treatment options vary depending on the severity, but typically include pentoxifylline and vitamin E as well as surgical debridement, with less evidence supporting hyperbaric oxygen therapy. Recognition and prompt treatment of ORN will allow for improved patient outcomes.

Impact on treatment time of MRI-based brachytherapy in two implants (4 doses) compared with CT-based brachytherapy in five implants for cervical cancer.

PURPOSE: Concurrent chemoradiotherapy and brachytherapy is the standard of care for locally advanced cervical cancer. Brachytherapy is an integral part of treatment and has improved overall survival. Research is needed to ascertain the planning modalities and schedules to best use resources and optimize treatment time course. We hypothesized that MRI-based brachytherapy when delivered with the described regimen would not prolong, and potentially shorten, overall treatment time as compared with CT-based brachytherapy. METHODS AND MATERIALS: This study was a single-institution retrospective review within the years 2008 through 2018. Patients with cervical cancer of any stage who underwent definitive chemoradiotherapy and either CT- or MRI-based brachytherapy were included. The primary outcome variable for this study was time (in days). Overall treatment time was defined as the number of days from the first until the last day of radiotherapy. Univariate analysis was performed using Stata statistical software. RESULTS: External beam radiotherapy doses were generally 45-50.4 Gy. CT-based and MRI-based brachytherapy were performed in 55 and 49 patients, respectively. The median treatment time for brachytherapy with CT-based planning was 19.0 days and with MRI-based planning was 9.0 days (p < 0.001). The median treatment time for total radiation therapy with CT-based planning was 53 days, and with MRI-based planning was 50 days (p = 0.781). CONCLUSIONS: This study found that MRI-based brachytherapy, when performed with the proposed regimen, did not prolong overall treatment time and significantly decreased time to complete brachytherapy in comparison with CT-based brachytherapy on nonconsecutive days. This regimen favorably impacts timely completion of treatment and uses MRI resources well within the construct of our institution.

A Medicare cost analysis of MRI- versus CT-based high-dose-rate brachytherapy of the cervix: Can MRI-based planning be less costly?

PURPOSE: While some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible. METHODS AND MATERIALS: We identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1-2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost. RESULTS: The median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13-$19,863.03, p < 0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14-$29,511.16, p < 0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p < 0.001). CONCLUSIONS: MRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application.

Delineating the relationship between Point A prescription dose and pelvic lymph node doses in intracavitary high-dose-rate brachytherapy treatment of cervical cancer for use in low- and middle-income countries.

PURPOSE: To define the relationship between the Point A prescription dose and the dose delivered to various pelvic lymph node groups during high-dose-rate (HDR) brachytherapy treatment of cervical cancer. In less developed countries, brachytherapy is often done without three-dimensional image guidance, instead relying on plain radiography and prescription to Point A. A defined relationship between Point A dose and lymph node doses would help physicians in these health care settings to more accurately estimate nodal doses. METHODS AND MATERIALS: Treatment data from 50 fractions of HDR brachytherapy of cervical cancer were reviewed, the pelvic lymph nodes were contoured, and dose-volume histogram parameters were obtained. Dose-volume histogram parameters for each contour were normalized as a percentage of the corresponding Point A dose. All nodal groups were divided into left and right sides, except the presacral nodal group. RESULTS AND CONCLUSIONS: Mean Point A doses were bilateral (Bil) 5.92 Gy ± 0.58, left (L) 5.93 ± 0.59, and right (R) 5.92 ± 0.59. Mean normalized D90 values for the various lymph node groups were as follows-obturator: Bil 20.3% ± 4.5, L 20.5% ± 4.4, and R 20.2% ± 5.2; external iliac: Bil 9.5% ± 2.9, L 10.0% ± 3.1, and R 9.5% ± 3.0; internal iliac: Bil 12.2% ± 3.5, L 12.1% ± 3.4, and R 12.9% ± 4.7; common iliac: Bil 4.3% ± 1.6, L 4.3% ± 1.6, and R 4.3% ± 1.7; and presacral: 8.7% ± 3.4. These relationships can serve as a useful tool for evaluating lymph node doses during HDR brachytherapy of cervical cancer in facilities performing two-dimensional treatment planning and those with limited resources.

Early outcomes and impact of a hybrid IC/IS applicator for a new MRI-based cervical brachytherapy program.

PURPOSE: The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program. METHODS: We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan-Meier method. RESULTS: Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis-free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09). CONCLUSIONS: There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.

Point A vs. HR-CTV D90 in MRI-based cervical brachytherapy of small and large lesions.

PURPOSE: To evaluate the dosimetric benefits of MRI-based brachytherapy in small and large high-risk clinical target volume (HR-CTV) in cervical cancer. METHODS AND MATERIALS: Twenty-eight fractions obtained from sixteen cervical cancer patients treated with MRI-based high-dose-rate brachytherapy with standard tandem and ovoid applicators were used; original fractions were optimized to HR-CTV D90. Fractions were separated based on the median volume into small and large (HR-CTV <25 cm3 or >25 cm3) lesion groups. Retrospective plans prescribed to Point A were created for each fraction. D0.1 cc, D2 cc, and International Commission of Radiation Unit and Measurements (ICRU) points were used to compare Point A vs. HR-CTV D90 plans for bladder, rectum, and sigmoid. RESULTS: In the small lesion group, Point A plans vs. HR-CTV D90 plans had significantly higher D0.1 cc, D2 cc, and ICRU points for bladder, rectum, and sigmoid (p < 0.05). In the large lesion group, there was no significant difference between Point A and HR-CTV D90 plans for D0.1 cc, D2 cc, and ICRU points to the organs at risk (OARs). CONCLUSIONS: The dosimetric advantages to OARs offered by MRI-based brachytherapy with prescription to HR-CTV D90 compared to Point A is most distinct for patients with smaller HR-CTV (<25 cm3). This study demonstrates sufficient tumor coverage with lower doses to OARs in HR-CTV D90 vs. Point A plans in the small lesion group. These improvements were not seen in the large lesion group, indicating a lesser dosimetric advantage of HR-CTV D90 compared to Point A planning when the cervical lesion is >25 cm3. Incorporation of interstitial needles for patients with larger HR-CTV is likely the best method to decrease dose to OARs and improve tumor coverage.

Bladder distension improves the dosimetry of organs at risk during intracavitary cervical high-dose-rate brachytherapy.

PURPOSE: To evaluate dose-volume histograms (DVHs) and dose-surface histograms (DSHs) to analyze bladder distension during cervical brachytherapy. METHODS: Twenty brachytherapy fractions from five cervical cancer patients were selected. For each fraction, empty and full (200cc of contrasted saline) bladder simulation CT scans existed, one of which was used to plan treatment. An alternative plan was then created with the unused scan. DVH for each fraction was generated for the bladder, rectum, sigmoid colon, and small bowel. Mean DVH dose, D0.1cc, and D2cc were calculated for each organ at risk. Plans were then exported to a MATLAB-based program to generate a DSH. RESULTS: Full bladder plans showed no difference in bladder D2cc or D0.1cc compared with empty bladder plans; however, bladder mean DVH dose and DSH dose were both significantly reduced. Full bladder plans showed a significant reduction in small intestine D2cc from 2.81 Gy to 1.83 Gy and reduction in D0.1cc from 4.07 Gy to 2.57 Gy (p < 0.05); similarly, sigmoid D2cc was significantly reduced from 4.24 Gy to 3.87 Gy (p < 0.05) and D0.1cc was reduced from 6.12 Gy to 5.61 Gy (p < 0.05) in full bladder plans. Both small intestine and sigmoid also showed reduced mean DVH and DSH dose in full bladder plans. The rectum showed no significant difference in D2cc, D0.1cc, mean DVH, or DSH dose between plans. CONCLUSIONS: Bladder distension during cervical brachytherapy significantly reduced dose in all DVH and DSH parameters for sigmoid and small intestine with no change in bladder parameters. It reduces dose to organ at risk, but the correlation to toxicity requires further investigation.