Interstitial brachytherapy for gynecologic malignancies: Complications,toxicities, and management

From both a disease and management perspective, locally advanced gynecologic cancers present a significant challenge. Dose escalation with brachytherapy serves as a key treatment, providing conformal radiation while sparing at-risk organs. Intracavitary brachytherapy techniques have been shown to be effective, with improving tumor control and toxicity profiles with the advent of three-dimensional image planning. Despite this, the variations in tumor size, location, and pelvic anatomy may lead to suboptimal dosimetry with standard intracavitary applicators in some clinical scenarios. The addition of interstitial needles (interstitial brachytherapy (interstitial brachytherapy) can improve the conformality of brachytherapy treatments by adding needles to peripheral (and central) regions of the target volume, improving the ability to escalate doses in these undercovered regions while sparing organs at risk. Interstitial brachytherapy can be delivered by intracavitary and interstitial hybrid applicators (ICBT/ISBT), perineal template (P-ISBT), or by free-hand technique. ISBT has however yet to be widely available because of concerns of complications and toxicities from this specialized treatment. However, with the increasing use of three-dimensional image-guided brachytherapy, there is an opportunity to increase the level of expertise in the gynecologic radiation oncology community with an improved understanding of the potential complications and morbidity. In this article, we review the acute and long-term toxicity in both ICBT/ISBT and P-ISBT using image-guided brachytherapy.     

Design and characterization of an intracavitary ultrasound hyperthermia applicator for recurrent or residual lesions in the vaginal cuff

For evaluating the feasibility of treating recurrent lesions in the vaginal cuff by hyperthermia, a 2-element ultrasound applicator was designed, constructed and characterized. A half-cylindrical transducer ( d = 1 cm, length = 1 cm) was used to construct the 2-element ultrasound applicator. Each element of this applicator was operated at 1.5 MHz and characterized by measuring transducer efficiency and acoustic power distribution. Thermocouple probes were used to measure the temperature rise in the phantom. The element sizes used in this study were selected to be comparable to a high dose rate brachytherapy colpostat applicator. Each element was powered separately to achieve a desired temperature pattern in a target. The acoustic output power as a function of applied electric power of elements 1 and 2 were linear over this 1-40 W range and efficiencies were 32.2 &#45 3.4% and 46.2 &#45 0.8%, respectively. The temperature measurements in the phantom showed that a 6°C temperature rise was achieved 2 cm from the applicator surface. As a conclusion, the ability of the ultrasound colpostat applicator to be used for hyperthermia was demonstrated by measuring acoustic output power, ultrasound field distribution and temperature rise in the phantom. Based on the characteristics of this applicator, it has the potential to be useful for inducing hyperthermia to the vaginal cuff in the clinic.     

High dose rate brachytherapy with customized applicators for malignant facial skin lesions

PurposeBrachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system.Material and methodsPatients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg^® Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10 mm to 20 mm). The dose schedules were 25 Gy in five fractions for postoperative lesions, 30 Gy in six fractions for exclusive treatments and a single session of 8 Gy could be considered for palliative treatments.ResultsIn 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1 cm² with a mean thickness of 6.1 mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg^® Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity.ConclusionHigh dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment.     

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement.     

A national surveillance study of the current status of reirradiation using brachytherapy in Japan

PurposeThis study aimed to explore the current status and pattern of practice for reirradiation using brachytherapy (ReRT-BT) through a survey in Japan.Materials and MethodsWe distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate brachytherapy facilities.ResultsWe received responses from 76 institutions (49.7%). Forty-three of these institutions performed ReRT-BT and 42 institutions (55%) performed ReRT-BT during 2009–2018. However, 29 of the 42 institutions (69%) reported difficulty in obtaining ReRT-BT case information from their respective databases. Almost all the institutions encountered insufficient database system to extract details about the ReRT-BT cases. Responses from 33 institutions included the number of ReRT-BT cases; this increased from 90 in the period 2009–2013 (institution median = 0.5; 0–16) to 172 in the period 2014–2018 (institution median = 2; 0–26). Nine institutions had to perform ReRT-BT for more than one case per year. The major location for cancer treatment was the pelvis (94%), followed by the head and neck (5%) and others (1%). In six site-specific scenarios, barring uterine corpus cancer recurrence, more than 90% of radiation oncologists agreed to perform ReRT-BT, whereas other areas (head and neck, prostate, and rectal cancer) gained 16–37% agreement.ConclusionsThis decade saw an increase in the number of ReRT-BT cases in Japan and radiation oncologists’ interest in ReRT-BT as a viable therapeutic option. However, scarce availability, immature education system, and insufficient database system are barriers to further consensus building.     

Derivation of in vivo source tracking error thresholds for TRUS-based HDR prostate brachytherapy through simulation of source positioning errors

PurposeThe purpose of this study was to simulate treatment planning source positioning errors in transrectal ultrasound–based real-time high-dose-rate prostate brachytherapy treatments and determine appropriate in vivo source tracking error thresholds.Methods and MaterialsTreatment planning source positioning errors were simulated for 20 patient plans in the brachytherapy treatment planning system by manually adjusting the dwell position coordinates within selected catheters without plan reoptimization. The change in dose-volume histogram (DVH) indices was calculated as a function of the source positioning error. The magnitude of the change in the DVH indices was then used to derive appropriate in vivo source tracking error thresholds.ResultsSource positioning error thresholds to prevent potentially significant changes in prostate (target) DVH metrics ranged from 2 to 5 mm, dependent on the direction of the source positioning error, as well as the relative weight of the dwell position within the plan, and its position relative to the patient anatomy. Source positioning error thresholds to prevent potentially clinically significant changes in organ at risk DVH metrics were found to be complex and patient-dependent.ConclusionsIn vivo source tracking error thresholds for transrectal ultrasound–based real-time high-dose-rate prostate brachytherapy were investigated via the simulation of treatment planning source positioning errors. These error thresholds were found to be dependent not only on the direction of the error, but also on the endpoint. There is still the potential for larger changes in DVH indices to occur for catheter shifts smaller than the proposed threshold levels in this study.     

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

PurposeA 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 MaterialsLiterature 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.ResultsData 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.ConclusionsAccrual 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.     

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy

PURPOSETo report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution.METHODSSeventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3–3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4–7 Gy given once or twice a week).RESULTSMedian follow-up was 76 months (7–204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9–54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation.CONCLUSIONSHDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.     

FMEA-guided transition from microSelectron to Flexitron for HDR brachytherapy

PurposeTo utilize failure mode and effects analysis (FMEA) to effectively direct the transition from the Elekta microSelectron to the Flexitron high dose-rate afterloader system.Materials and MethodsOur FMEA was performed in two stages. In the first stage, the lead brachytherapy physicists used FMEA to guide the brainstorming sessions and to identify vulnerabilities during this transition. The second stage of FMEA was carried out 2 months after the clinical release of the Flexitron system. The process map was examined again to further refine and improve the entire process.ResultsIn the first-stage FMEA, 81 process steps were identified. Moreover, 80 failure modes and their categorized causes were recognized. Checklists and data books containing the corresponding applicator information were verified and updated. Next, based on outcomes of our first-stage FMEA, we chose to implement the commissioning process in two phases. The second stage of FMEA identified error-prone steps in our newly updated processes. This second stage of analysis resulted in the development of new tools and checklist items.ConclusionsThe two-stage FMEA approach successfully directed the transition to the Flexitron system by identifying the necessary changes in the checklists and workflows for all applicators utilized in our clinic. It also led to the decision to use a two-phase commissioning approach. This allowed for minimization clinical downtime, avoidance of an extra source change, and facilitation of efficient staff training. Additionally, multiple project-level failures were discovered. Our experience and outcomes from this FMEA-guided transition should provide valuable information to the brachytherapy community.     

Hypoparathyroidism,deafness, and renal dysplasia syndrome: 20 Years after the identification of the first GATA3 mutations

The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by heterozygous mutations of the GATA3 gene. In the last 20 years, since the identification of the genetic cause of the HDR syndrome, GATA3 mutations have been reported in 124 families (177 patients). The clinical aspects and molecular genetics of the HDR syndrome are reviewed here together with the reported mutations and phenotypes. Reported mutations consist of 40% frameshift deletions or insertions, 23% missense mutations, 14% nonsense mutations, 6% splice‐site mutations, 1% in‐frame deletions or insertions, 15% whole‐gene deletions, and 1% whole‐gene duplication. Missense mutations were found to cluster in the regions encoding the two GATA3 zinc‐finger domains. Patients showed great clinical variability and the penetrance of each HDR defect increased with age. The most frequently observed abnormality was deafness (93%), followed by hypoparathyroidism (87%) and renal defects (61%). The mean age of diagnosis of HDR was 15.3, 7.5, and 14.0 years, respectively. However, patients with whole‐gene deletions and protein‐truncating mutations were diagnosed earlier than patients with missense mutations.