A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer.

INTRODUCTION: The purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODS: This cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTS: The 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze ("mild/moderate" 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently "excellent/good" with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently "extremely easy" with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSION: This randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Novel Form of Breast Intraoperative Radiation Therapy with CT-Guided High-Dose-Rate Brachytherapy: Interim Results of a Prospective Phase-II Clinical Trial.

BACKGROUND: Precision breast intraoperative radiation therapy (PB-IORT) is a novel method of IORT that uses customized CT-based treatment plans and high-dose-rate (HDR) brachytherapy. We conducted a phase-II multi-institution trial to evaluate the efficacy of PB-IORT. STUDY DESIGN: Between 2015 and 2022, 3 centers enrolled women aged 45 years and older with invasive or in situ carcinoma measuring 3 cm or smaller and N0 status (n = 358). Breast-conserving surgery was performed, and a multilumen balloon catheter was placed in the lumpectomy bed. CT images were used to create customized HDR brachytherapy plans that delivered 12.5 Gy to the tumor bed. The primary outcome assessed was the 5-year rate of index quadrant tumor recurrence. An interim analysis was conducted after one-third of eligible participants completed 5 years of follow-up. This trial is registered with clinicaltrials.gov (NCT02400658). RESULTS: The cohort comprised 153 participants with a median age of 64 years and median follow-up time of 5.9 years. The estimated 5-year index quadrant tumor recurrence rate and overall survival were 5.08% (95% CI 2.23 to 9.68) and 95.1%, respectively. Locoregional (ipsilateral breast and axilla) and distant recurrence rates were each 1.96%. Seven deaths occurred during the first 5 years of follow-up, with only 1 attributable to breast cancer. Overall, 68.6% of patients experienced any adverse effects, and 4 cases of breast-related severe toxicities were observed. CONCLUSIONS: This study presents the results of a planned interim analysis of a phase-II trial investigating PB-IORT and demonstrates the efficacy and safety of single-fraction, CT-based, HDR brachytherapy after breast-conserving surgery. These findings provide valuable insights into the use of PB-IORT as a treatment modality.

AAPM medical physics practice guideline 13.a: HDR brachytherapy, part A.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee April 28, 2022.

Evaluating the relationship between vaginal apex "dog ears" and patterns of recurrence in endometrial cancer following adjuvant image guided vaginal cuff brachytherapy.

PURPOSE: The aim of this investigation is to characterize vaginal apex "dog ears" and their association with patterns of treatment failure in patients with endometrial cancer treated with adjuvant high-dose-rate (HDR) single-channel vaginal cuff brachytherapy (VCB). METHODS: A retrospective review of patients treated with HDR VCB from 2012 to 2021 for medically operable endometrial cancer at a single institution was conducted. Dog ears, defined as tissue at the apex extending at least 10 mm from the brachytherapy applicator were identified on CT simulation images. Fisher exact test and a multivariate logistic regression model evaluated the association between factors of interest with treatment failure. Vaginal cuff failure free survival (VCFFS) was calculated from first brachytherapy to vaginal cuff recurrence (VCR). RESULTS: A total of 219 patients were reviewed. In this sample, 57.5% of patients met criteria for having dog ears. In total, 13 patients (5.9%) developed a VCR. There was no statistically significant difference in the rate of VCR between patients with and without dog ears (7.1% vs. 4.3%, p = 0.56). There was a trend toward increased risk of recurrence with higher grade histology identified in the multivariate logistic regression model (p = 0.085). The estimated 3-year probability of VCFFS was 86%. CONCLUSIONS: Vaginal apex dog ears are prevalent but are not found to statistically increase the risk of VCR after VCB in our single institution experience. However, while local failure remains low in this population, we report an absolute value of over twice as many VCRs in patients with dog ears, indicating that with improved dog ear characterization this may remain a relevant parameter for consideration in treatment planning.

Dose differentiated high-dose-rate prostate brachytherapy: a feasibility assessment of MRI-guided dose escalation to dominant intra-prostatic lesions.

Purpose: Prostate brachytherapy is routinely performed with trans-rectal ultrasound (TRUS)- or computed tomography (CT)-based planning that cannot delineate dominant intra-prostatic lesions (DILs). In contrast, magnetic resonance imaging (MRI)-based planning allows for more accurate DIL delineation and dose escalation. This study assessed the maximum achievable dose escalation to DILs. Material and methods: We retrospectively identified 24 patients treated with high-dose-rate (HDR) prostate brachytherapy boost (15 Gy in 1 fraction). All patients had a pre-treatment prostate MRI with 1-3 DILs. MRIs were used to delineate DILs and were co-registered to TRUS intra-procedure. Treatment plans were experimentally re-optimized to escalate DIL dose. Dosimetric indices from the original and re-optimized plans were compared using two-tailed paired t-test. Re-optimized plans were deemed acceptable if they achieved all of the following criteria: prostate D90 > 100%, prostate V100 > 90%, urethra D10 < 118%, rectum V80 < 0.5 cc, bladder D1cc < 75%, or if they did not exceed organs at risk (OARs) doses of the original plan. Results: The mean DIL D90 was significantly increased from 134% of the prescription dose on the original plans to 154% on the re-optimized plans. The mean urethra D10 and mean bladder D1cc were significantly reduced from 123% to 117% and from 72% to 65%, respectively. Prostate D90 was reduced from 106% to 102%, and prostate V100 was reduced from 93% to 91%. Conclusions: We re-optimized HDR brachytherapy plans to escalate DILs dose to a mean D90 of > 150% while maintaining favorable prostate coverage and OARs doses. We propose DIL D90 dose of > 150% (22.5 Gy) as an achievable goal.

A comparative study using time-driven activity-based costing in single-fraction breast high-dose rate brachytherapy: An integrated brachytherapy suite vs. decentralized workflow.

INTRODUCTION: Precision breast intraoperative radiation therapy (PB-IORT) is a novel approach to adjuvant radiation therapy for early-stage breast cancer performed as part of a phase II clinical trial at two institutions. One institution performs the entire procedure in an integrated brachytherapy suite which contains a CT-on-rails imaging unit and full anesthesia capabilities. At the other, breast conserving surgery and radiation therapy take place in two separate locations. Here, we utilize time-driven activity-based costing (TDABC) to compare these two models for the delivery of PB-IORT. METHODS: Process maps were created to describe each step required to deliver PB-IORT at each institution, including personnel, equipment, and supplies. Time investment was estimated for each step. The capacity cost rate was determined for each resource, and total costs of care were then calculated by multiplying the capacity cost rates by the time estimate for the process step and adding any additional product costs. RESULTS: PB-IORT costs less to deliver at a distributed facility, as is more commonly available, than an integrated brachytherapy suite ($3,262.22 vs. $3,996.01). The largest source of costs in both settings ($2,400) was consumable supplies, including the brachytherapy balloon applicator. The difference in costs for the two facility types was driven by personnel costs ($1,263.41 vs. $764.89). In the integrated facility, increased time required by radiation oncology nursing and the anesthesia attending translated to the greatest increases in cost. Equipment costs were also slightly higher in the integrated suite setting ($332.60 vs. $97.33). CONCLUSIONS: The overall cost of care is higher when utilizing an integrated brachytherapy suite to deliver PB-IORT. This was primarily driven by additional personnel costs from nursing and anesthesia, although the greatest cost of delivery in both settings was the disposable brachytherapy applicator. These differences in cost must be balanced against the potential impact on patient experience with these approaches.

Comparison of initial computed tomography-based target delineation and subsequent magnetic resonance imaging-based target delineation for cervical cancer brachytherapy.

PURPOSE: For cervical brachytherapy planning, magnetic resonance imaging (MRI) is preferable to computed tomography (CT) for target delineation. However, due to logistical and financial restrictions, in-room MRI is sometimes not routinely available in brachytherapy centers. Our institution has created a workflow that integrates MRI-based target delineation with an in-room CT scanner, with the aim of improving target coverage and conformality. This study reports the initial dosimetric results with using this workflow. MATERIAL AND METHODS: A retrospective review was performed on 46 consecutive patients who received definitive chemoradiation with 5 fraction intracavitary high-dose-rate (HDR) brachytherapy for cervical cancer. Fraction 1 was planned from CT only. Outpatient MRI was obtained after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumor response. This MRI was registered to the CT for planning fractions 2-5. The median prescription dose for the cohort was 25 Gy (range, 25-29 Gy). RESULTS: The D90 to the high-risk clinical target volume (HR-CTV) and D2cc rectal dose were increased from fraction 1 to fraction 2-5 averaged (p < 0.05). Among the 18 patients with complete volumetric data, there was no significant difference in HR-CTV size, with an average decrease of 1.73 cc (p > 0.05) with MRI fusion. Eleven out of 18 patients had changes in high-risk target volume greater than 20%, with an absolute average change in volume of 31.5%. CONCLUSIONS: The use of asynchronous MRI for target delineation, with co-registration to CT for each fraction of brachytherapy was associated with higher D90 to the HR-CTV. We observed slightly higher D2cc rectal doses with MRI, but cumulative rectal doses were within accepted thresholds. High-risk target volumes were not consistently increased or decreased, but MRI fusion was associated with target volume changes greater than 20% in over half of the treated patients.

Time-driven activity-based costing of a novel form of CT-guided high-dose-rate brachytherapy intraoperative radiation therapy compared with conventional breast intraoperative radiation therapy for early stage breast cancer.

INTRODUCTION: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy. METHODS AND MATERIALS: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries. RESULTS: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy. CONCLUSIONS: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy.

Normal tissue dose and risk estimates from whole and partial breast radiation techniques.

PURPOSE: To compare radiation dose to organs at risk in patients with early-stage breast cancer treated with lumpectomy and intraoperative radiation therapy with CT-guided HDR brachytherapy (precision breast IORT; PB-IORT) and those treated with external beam whole breast irradiation (WB-DIBH) or partial breast irradiation (PB-DIBH) with deep inspiratory breath hold. METHODS: We retrospectively identified 52 consecutive patients with left-sided breast cancers treated with either PB-IORT (n = 17, 76% outer breast) on a phase I clinical trial, adjuvant PB-DIBH (n = 18, 56% outer breast, 6% cavity boost), or WB-DIBH (n = 17, 76% outer breast, 53% with lumpectomy cavity boost). Conventional (2 Gy/fraction) or moderate hypofractionation (2.66 Gy/fraction) was prescribed for the external beam cohorts and 12.5 Gy in 1 fraction to 1 cm from the balloon surface was prescribed to the HDR brachytherapy cohort. CT-based planning was used for all patients. Organ at risk doses and excess risk ratios (ERR) for secondary lung cancers, contralateral breast cancers, and cardiac toxicity were compared between treatment techniques. RESULTS: Compared to WB-DIBH and PB-DIBH, PB-IORT resulted in lower ipsilateral lung V5, V10, V20, mean, and max dose (P < .05). Mean ipsilateral lung BED3Gy was as follows: 1.32 Gy for PB-IORT, 4.33 Gy for WB-DIBH, 3.35 Gy for PB-DIBH. The ERR for lung cancer was lowest for PB-IORT (P < .001). There was significantly higher contralateral breast max dose but lower mean BED3Gy for WB-DIBH compared with PB-IORT (P = .012, P = .011, respectively). Mean contralateral breast BED3Gy was as follows: 0.10 Gy for PB-IORT, 0.06 Gy for WB-DIBH, and 0.08 Gy for PB-DIBH. The ERR for contralateral breast cancer was low for all breast techniques, but WB-DIBH showed lower ERR compared to PB-IORT (P = .019). Mean heart BED2Gy was higher with PB-IORT at 1.26 Gy compared to 0.48 Gy and 0.24 Gy for WB-DIBH and PB-DIBH, respectively (P < .001). CONCLUSIONS: Patients with early-stage breast cancer treated with PB-IORT and with tissue-sparing external beam techniques all received low organ at risk doses, but PB-IORT resulted in far lower ipsilateral lung dose compared with external beam techniques. Our data indicate the lowest mean contralateral breast BED in the WB-DIBH group, likely due to the simplicity of the field design in low-risk patients using tangential whole breast radiation. External beam using DIBH results in lowest heart dose, but all techniques were well within recommended heart constraints.

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite.

PURPOSE: Adjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails. METHODS AND MATERIALS: Process maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen. RESULTS: The total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes. CONCLUSIONS: Time-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation.

Implementation of an HDR brachytherapy-based breast IORT program: Initial experiences.

PURPOSE: A multidisciplinary team at our institution developed a novel method of intraoperative breast radiation therapy (precision breast intraoperative radiation therapy [PB-IORT]) that uses high-dose-rate brachytherapy with CT on-rails imaging to deliver high-dose, customized radiotherapy to patients with early-stage breast cancer. This report summarizes our program's experience developing and implementing PB-IORT. METHODS AND MATERIALS: Literature on PB-IORT was reviewed including published articles and abstracts. To evaluate case volume, all patients with a breast cancer diagnosis who underwent breast surgery or breast radiation (2010-2017) at our academic institution were identified. Patients were stratified into pre-IORT and post-IORT eras with initiation of our PB-IORT program in October 2013. Overall trends in surgical and radiation therapy volume in each era were analyzed by linear regression. Travel distance for all surgical patients was calculated using Google Maps (Alphabet Inc.) and then compared between IORT and non-IORT patients. RESULTS: Data from a PB-IORT Phase 1 trial found that the primary endpoints were met and that PB-IORT is feasible and safe. The direct health system's delivery costs for PB-IORT exceed those of 16-fraction whole-breast irradiation when accounting for consumable supplies (multilumen balloon applicator = $2,750 per patient). There was a significant increase in yearly growth of breast cancer surgical volume with PB-IORT. CONCLUSIONS: Accrual rates for the ongoing Phase II trial have been quicker than expected in an area where more research is needed. The rapid accrual indicates patient interest and demand for this treatment and that it is very feasible to get more data from randomized trials.

Development and preclinical testing of a novel biodegradable hydrogel vaginal packing technology for gynecologic high-dose-rate brachytherapy.

PURPOSE: We evaluated the performance of a novel hydrogel-based strategy developed for clinical use as vaginal packing using phantoms and cadavers, and to compare the hydrogel to gauze and balloon packing. MATERIAL AND METHODS: The biocompatible hydrogel is based on a thiol-Michael addition reaction, with delivery of reagents into the vaginal cavity using a custom-made system. Soft-cured cadavers were used for soft tissue-like mechanical properties. Two cadavers with intact uteri had magnetic resonance imaging (MRI) compatible with tandem and ovoids. For one cadaver, the temperature of the vaginal canal was measured before hydrogel application, during polymerization, and after hydrogel removal. The hydrogel packing and applicator was kept in a second cadaver, which was imaged using computed tomography (CT) and MRI. The hydrogel packing and imaging was repeated for an open multichannel MRI compatible, titanium-based vaginal cylinder placed in a post-hysterectomy cadaver. RESULTS: The gel reaction occurred within 90 seconds, indicating polymerization at clinical quantities with a 5°C increase in vaginal temperature. CT and MRI imaging identified the hydrogel readily and showed a conformance to anatomy with few air pockets. The entire hydrogel packing was readily retrieved upon completion of imaging. CONCLUSIONS: The novel strategy for polyethylene glycol (PEG)-based hydrogel intra-vaginal packing was able to rapidly polymerize in human cadavers with minimal heat production. Delivery was efficient and able to fill the contours of the vaginal cavity and displace tissue away from the applicator axis. The hydrogel has favorable imaging characteristics on CT and MRI, and shows a potential for clinical use, warranting additional studies for the use in humans.

Utility of CT imaging in a novel form of high-dose-rate intraoperative breast radiation therapy.

INTRODUCTION: Intraoperative radiation therapy (IORT) is an alternative to whole breast radiation following breast conserving surgery. Conventional breast IORT is limited by lack of cross-sectional imaging. In response, our institution developed Precision Breast IORT (PB-IORT) which utilizes intraoperative computed tomography (CT) images for confirmation of brachytherapy applicator placement and for treatment planning. The purpose of this study was to determine the utility of CT imaging in PB-IORT in the first 103 patients treated in two prospective clinical trials. METHODS: We retrospectively reviewed the first 103 patients treated with PB-IORT. All patients underwent breast surgery and placement of a multi-lumen brachytherapy applicator. Patients had a CT scan followed by high-dose-rate (HDR) brachytherapy. Endpoints were the number of patients having more than one CT during PB-IORT and the number of treatment plans having image-based modifications. RESULTS: After initial CT scan, 27 patients (26.2%) had findings prompting surgical applicator adjustment. One patient underwent an additional scan to localize a biopsy clip and aid in excision to negative margin. Eighty-one patients (78.6%) had dosimetry modifications based on CT findings with 36 plans (35.0%) adjusted to protect the skin or chest wall and 45 plans (43.7%) to protect both the skin and chest wall. CONCLUSIONS: Computed tomography findings prompted treatment alterations in the majority of patients treated with PB-IORT to enhance tissue conformity and to sculpt the radiation dose away from normal tissues. CT imaging is unique to PB-IORT. These findings suggest the potential clinical superiority of PB-IORT given its allowance for patient-specific alterations.

Comparison of heart dose in early-stage left-sided breast cancers treated with intraoperative radiation therapy or whole-breast irradiation with deep inspiratory breath hold.

PURPOSE: To compare heart dose between patients treated with lumpectomy and either intraoperative radiation therapy (IORT) with CT-guided high-dose-rate brachytherapy (precision breast IORT [PB-IORT]) or whole-breast irradiation with deep inspiratory breath hold (WBI-DIBH) for early-stage left-sided breast cancers. METHODS AND MATERIALS: We retrospectively identified the 17 patients with left-sided breast cancers treated with PB-IORT on a phase I clinical trial and 17 patients with left-sided tumors who had undergone lumpectomy and adjuvant WBI-DIBH. Dosimetric data were obtained. T-testing was performed and biologically effective doses (BEDs) were calculated using an α/ß ratio of 2 Gy. RESULTS: Mean heart dose was significantly lower with WBI-DIBH compared with PB-IORT (0.61 vs. 0.87 Gy, p = 0.006). Mean heart BED was lower with WBI-DIBH (0.62 vs. 1.3 Gy2, p = 0.0001). Nominal maximum heart dose was higher with WBI-DIBH (11.37 vs. 4.81 Gy, p = 0.004). Maximum heart dose BED was similar between WBI-DIBH and IORT, 16.63 vs. 19.36 Gy (p = 0.64), respectively. No difference was found in mean left anterior descending artery dose: 2.18 Gy with WBI-DIBH and 1.89 Gy with IORT (p = 0.446). The maximum left anterior descending doses were 9.63 Gy and 3.62 Gy with WBI-DIBH and IORT, respectively (p = 0.016). Distance from the heart to the lumpectomy cavity was inversely associated with heart dose for PB-IORT, but not for WBI-IORT. CONCLUSIONS: Heart doses were low in both groups. Expected increase in cardiac risk at these doses is minimal. It is unlikely that there will be a clinically significant difference in cardiac toxicity in patients treated with WBI-DIBH or PB-IORT. Further research is needed to evaluate the actual clinical impact of the observed cardiac doses delivered with these modalities.

High dose-rate tandem and ovoid brachytherapy in cervical cancer: dosimetric predictors of adverse events.

BACKGROUND: Brachytherapy (BT) is a vital component of the curative treatment of locally advanced cervical cancer. The American Brachytherapy Society has published guidelines for high dose rate (HDR) BT with recommended dose limits. However, recent reports suggest lower doses may be needed to avoid toxicity. The purpose of this study is to investigate incidence and predictive factors influencing gastrointestinal (GI) and genitourinary (GU) toxicity following HDR intracavitary brachytherapy for locally advanced cervical cancer. METHODS: We retrospectively evaluated a cohort of patients with locally advanced cervical cancer who received CT-based HDR BT. Cumulative doses were calculated using the linear-quadratic model. Statistical analyses were used to investigate clinical and dosimetric predictors of GI and GU toxicity following HDR brachytherapy according to CTCAE v4.0 grading criteria. RESULTS: Fifty-six women with FIGO IB1 - IVA cervical cancer were included. The overall rate of any GU adverse event (Grade 1+) was 23.3% (n = 13) and severe adverse events (Grade 3+) was 7.1% (n = 4). Of those, the bladder equivalent dose in 2- Gray (Gy) fractions (EQD2) D2cc was ≥80 for three of the four patients. The overall rate of any GI adverse event was 26.8% (n = 15) and the rate of severe adverse events was 14.3% (n = 8). Of those, six of the eight patients had a rectal EQD2 D2cc ≥ 65 Gy and seven patients had a sigmoid D2cc ≥ 65 Gy. Amongst clinically meaningful factors for development of adverse events (i.e. diabetes, smoking status, ovoid size, and treatment duration), there were no statistically significant prognostic factors identified. CONCLUSIONS: Severe adverse events are observed even with adherence to current ABS guidelines. In the era of recent multi-institutional study results, our data also supports more stringent dosimetric goals. We suggest cumulative D2cc dose limits of: less than 80 Gy for the bladder and less than 65 Gy for the rectum and sigmoid.

Integration of MRI target delineation into rapid workflow cervical cancer brachytherapy: Impact on clinical outcomes.

INTRODUCTION: We evaluated the impact of MRI-based target delineation on toxicity and tumour control after implementation of a protocol to incorporate MRI while minimizing impact on overall procedural time. METHODS: We retrospectively reviewed outcomes for a cohort of 96 consecutive patients who received intracavitary brachytherapy for cervical cancer at our institution during 2012-2016. Starting in October 2014, an outpatient MRI was obtained for patients after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumour response. Then, for subsequent fractions, the MRI was co-registered by the Smit sleeve to the planning CT for target volume delineation. The primary and secondary outcomes were toxicity and local control, respectively. RESULTS: Median follow-up for the pre- (n = 50) and post-MRI-based (n = 46) planning groups was 24.6 and 14.7 months, respectively. Median treatment duration for patients before and after MRI implementation was 56 and 58 days (P = 0.052), respectively. Cumulative rectal D2 cc was less for those with MRI-based target delineation (P = 0.005). On multivariable analysis, patients with MRI-based target delineation experienced fewer severe late (CTCAE grade ≥ 3) toxicities (P = 0.025, hazard ratio = 0.25). Local control was 86% and 91% of the pre- and post-MRI groups, respectively (P = 0.959). CONCLUSIONS: Preliminary findings using this technique, which is applicable to other institutions without in-room MRI availability, are associated with lower radiation prescription doses, lower rectal doses and favourable toxicity rates while maintaining a rapid workflow. Longer follow-up is required to confirm equivalent local control.

Time-driven activity-based cost comparison of prostate cancer brachytherapy and intensity-modulated radiation therapy.

PURPOSE: To evaluate the delivery cost of frequently used radiotherapy options offered to patients with intermediate- to high-risk prostate cancer using time-driven activity-based costing and compare the results with Medicare reimbursement and relative value units (RVUs). METHODS AND MATERIALS: Process maps were created to represent each step of prostate radiotherapy treatment at our institution. Salary data, equipment purchase costs, and consumable costs were factored into the cost analysis. The capacity cost rate was determined for each resource and calculated for each treatment option from initial consultation to its completion. Treatment options included low-dose-rate brachytherapy (LDR-BT), combined high-dose-rate brachytherapy single fraction boost with 25-fraction intensity-modulated radiotherapy (HDR-BT-IMRT), moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost. RESULTS: The total cost to deliver LDR-BT, HDR-BT-IMRT, moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost was $2719, $6517, $4173, $5507, and $5663, respectively. Total reimbursement for each course was $3123, $10,156, $7862, $9725, and $10,377, respectively. Radiation oncology attending time was 1.5-2 times higher for treatment courses incorporating BT. Attending radiation oncologist's time consumed per RVU was higher with BT (4.83 and 2.56 minutes per RVU generated for LDR-BT and HDR-BT-IMRT, respectively) compared to without BT (1.41-1.62 minutes per RVU). CONCLUSIONS: Time-driven activity-based costing analysis identified higher delivery costs associated with prostate BT compared with IMRT alone. In light of recent guidelines promoting BT for intermediate- to high-risk disease, re-evaluation of payment policies is warranted to encourage BT delivery.

Evaluation of Delivery Costs for External Beam Radiation Therapy and Brachytherapy for Locally Advanced Cervical Cancer Using Time-Driven Activity-Based Costing.

PURPOSE: To evaluate the delivery costs, using time-driven activity-based costing, and reimbursement for definitive radiation therapy for locally advanced cervical cancer. METHODS AND MATERIALS: Process maps were created to represent each step of the radiation treatment process and included personnel, equipment, and consumable supplies used to deliver care. Personnel were interviewed to estimate time involved to deliver care. Salary data, equipment purchasing information, and facilities costs were also obtained. We defined the capacity cost rate (CCR) for each resource and then calculated the total cost of patient care according to CCR and time for each resource. Costs were compared with 2016 Medicare reimbursement and relative value units (RVUs). RESULTS: The total cost of radiation therapy for cervical cancer was $12,861.68, with personnel costs constituting 49.8%. Brachytherapy cost $8610.68 (66.9% of total) and consumed 423 minutes of attending radiation oncologist time (80.0% of total). External beam radiation therapy cost $4055.01 (31.5% of total). Personnel costs were higher for brachytherapy than for the sum of simulation and external beam radiation therapy delivery ($4798.73 vs $1404.72). A full radiation therapy course provides radiation oncologists 149.77 RVUs with intensity modulated radiation therapy or 135.90 RVUs with 3-dimensional conformal radiation therapy, with total reimbursement of $23,321.71 and $16,071.90, respectively. Attending time per RVU is approximately 4-fold higher for brachytherapy (5.68 minutes) than 3-dimensional conformal radiation therapy (1.63 minutes) or intensity modulated radiation therapy (1.32 minutes). CONCLUSIONS: Time-driven activity-based costing was used to calculate the total cost of definitive radiation therapy for cervical cancer, revealing that brachytherapy delivery and personnel resources constituted the majority of costs. However, current reimbursement policy does not reflect the increased attending physician effort and delivery costs of brachytherapy. We hypothesize that the significant discrepancy between treatment costs and physician effort versus reimbursement may be a potential driver of reported national trends toward poor compliance with brachytherapy, and we suggest re-evaluation of payment policies to incentivize quality care.

Prostate cancer high dose-rate brachytherapy: review of evidence and current perspectives.

INTRODUCTION: Patients with intermediate to high risk disease (prostate specific antigen (PSA) ≥ 10, Gleason score ≥ 7, or clinical stage ≥ T2b) suffer from poorer long-term biochemical control (freedom from an increasing prostate specific antigen level) when treated with external beam radiation (EBRT) alone. In order to improve biochemical control while limiting long-term complications, brachytherapy has been incorporated into radiotherapy treatment, either alone or in combination with EBRT. AREAS COVERED: Current literature regarding the use of high dose-rate (HDR) brachytherapy for localized prostate cancer, including as a boost and monotherapy. The efficacy and toxicities of various approaches are evaluated including comparisons to low dose-rate (LDR) brachytherapy. EXPERT COMMENTARY: Prostate HDR brachytherapy has higher conformality than EBRT, potentially improving the therapeutic ratio by allowing higher doses per fraction to tumor cells. The improved biochemical control shown in trials have resulted in EBRT plus brachytherapy to be included as a standard treatment option supported by the NCCN and ASCO guidance documents for intermediate to high risk prostate cancer.

Intraoperative radiation therapy for breast cancer patients: current perspectives.

Accelerated partial breast irradiation (APBI) provides an attractive alternative to whole breast irradiation (WBI) through normal tissue radiation exposure and reduced treatment duration. Intraoperative radiation therapy (IORT) is a form of APBI with the shortest time interval, as it delivers the entirety of a planned radiation course at the time of breast surgery. However, faster is not always better, and IORT has been met with healthy skepticism. Patients treated with IORT have an increased compliance and overall satisfaction when compared to patients treated with WBI. However, early randomized trial results demonstrated an increased rate of recurrence after IORT, slowing its widespread adoption. Despite these controversies, IORT utilization is increasing nationally and several novel developments are aimed at continuing to minimize the risk of recurrence and treatment-related toxicity while maximizing the patient experience.