Brachytherapy Techniques Research Articles

Image-guided adaptive brachytherapy for advanced cervical cancer spreading to the bladder and/or rectum: Clinical outcome and prognostic factors

IntroductionRefinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT. Materials and methodsMedical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (D90 CTVHR) and intermediate-risk target volume (D90 CTVIR), as well as the dose received by the most exposed 2 cm3 of the organs at risk. A Cox regression model was used to study the potential associations between clinical and dosimetric factors with survival endpoints and fistula formation. Results and statistical analysisA total of 81 patients were identified. All patients received pelvic+/− para-aortic radiotherapy, 45 Gy in 25 fractions +/− boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median D90 CTVHR dose was 75.5 GyEQD2 (SD: 10.39 GyEQD2) and median CTVHR volume was 47.6 cm3 (SD: 27.9 cm3). Median bladder and rectal D2cm3 dose were 75.04 GyEQD2 (SD: 8.72 GyEQD2) and 64.07 GyEQD2 (SD: 6.68 GyEQD2). After a median follow-up of 27.62 ± 25.10 months, recurrence was found in 34/81 patients (42%). Metastatic failure was the most common pattern of relapse (n = 25). Use of a combined interstitial/intracavitary technique and D90 CTVHR ≥ 75.1 GyEQD2 were prognostic factors for OS in univariate analysis (HR = 0.24, 95%IC: 0.057–1, p = 0.023; HR = 0.2, 95%IC: 0.059–0.68, p = 0.0025, respectively). In multivariate analysis, a D90 CTVHR ≥ 75.1 GyEQD2 was significant for OS (HR = 0.23; 95%IC: 0.07, 0.78, p = 0.018). The occurrence of vesicovaginal fistula (VVF) was the most frequent pattern of local recurrence (HR = 4.6, 95%CI: 1.5–14, p = 0.01). ConclusionAdvances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.

Evaluation of the Dosimetric Parameters of the Interstitial HDR Liver Brachytherapy at USM

There are numerous treatment options available to treat hepatocellular carcinoma (HCC). Up to now, stereotactic body radiotherapy (SBRT) has been considered the best option to cure the HCC, however SBRT does not adequately spare the nearby organ at risk (OAR) [1]. A high dose rate interstitial brachytherapy (HDR IBT) technique for HCC is considered as an alternative to the SBRT due to accurate and precise dose delivery to the target and well spared adjacent OAR [2]. The main objective of this retrospective study was to evaluate the dosimetry tolerance for the tumour and OAR for HDRIBT technique for HCC technique using the iridium-192 (Ir-192) source.
 A computed tomography (CT) image-guided for 41 patients with 71 treatment cases in USM were used to analyse the dose distribution in tumour (HCC) and the OAR (diaphragm). The computed dosimetry data from the Oncentra treatment planning system (v.4.3) was used to analyse the relationship between the dosimetric variables, of the prescribed dose (15 Gy – 25 Gy) and fractionation used for the HDRIBT for HCC by statistical analysis.
 In this study, 95% of the gross tumour volume (GTV) of HCC adequately achieved the prescribed dose in both single and multiple fractionations. The GTV dose decreased as the GTV volume increased for all the prescribed doses. Apart from that, the prescribed doses, 20 Gy and 25 Gy, exhibited a higher diaphragm dose in single fractionation treatment compared to 15 Gy dose. Meanwhile, the multiple fractionations treatment also exhibited a remarkably high diaphragm dose compared to the single fractionation treatment.
 The minimum GTV dose recommended was based on a comparison with the RTOG 0438, liver SBRT protocol. These recommended values were applicable in both single and multiple fractionations. In addition, it is also applicable in a prescribed dose of 15y – 25 Gy. In short, the minimum recommended GTV doses were the V99% 90% of the prescribed dose, V95% 95% of the prescribed dose V90% 100% of the prescribed dose, respectively. Meanwhile, the diaphragm tolerance dose in this study was compared with RTOG 0438 protocol of ribs tolerance dose, within 54 Gy. Therefore, the diaphragm tolerance dose recommended for diaphragm volume of 0.2cm3, 0.5cm3 and 2.0cm3 (15 Gy prescribed dose) < 10 Gy, (20 Gy prescribed dose) < 15 Gy and (25 Gy prescribed dose) < 20 Gy in single fractionation respectively for all prescribed dose, whereas for the multiple fractionations < 54 Gy, regardless of the GTV volume. In conclusion, HDRIBT technique for HCC is the most promising technique by maximizing the dose to the GTV and reducing dose to the diaphragm by both single and multiple fractionations.

What is appropriate target delineation for MRI-based brachytherapy for medically inoperable endometrial cancer?

PURPOSEFor medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. METHODS AND MATERIALSFor all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method. RESULTSThirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%–89.3%) at 12 months and 65.8% (95% CI 48.4%–83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%–100%) at 12 months and 88.8% (95% CI 86.6%–91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis). CONCLUSIONSPatients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.

Friday, June 17, 20224:00 PM - 5:00 PM MSPP01 Presentation Time: 4:00 PM: A Feasibility Study on Utilizing Cadaveric Models at a Network of Brachytherapy Research and Training Centers to Encourage Development and Widespread Use of Novel Robotic Bladder Cancer Brachytherapy Techniques

<h3>Purpose</h3> This feasibility study outlines a proof-of-concept model – the Houston Methodist Institute for Technology, Innovation & Education (MITIE) – for the use of cadaveric models at research centers to encourage development and training of novel robotic brachytherapy techniques, thereby expediting the incorporation of brachytherapy into the standard of care for muscle-invasive bladder cancer (MIBC). <h3>Materials and Methods</h3> Catheter insertion sites were marked on a male cadaver, and the da Vinci Surgical System(R) (Intuitive Surgical, Inc., Sunnyvale, CA) was docked. A modified catheter-needle system was assembled since pre-assembled bladder-specific catheter-needle systems are not compatible with all brachytherapy afterloaders. Closed-end catheters were inserted into 17-gauge curved needles. The first catheter was placed into the right lateral hypogastric abdominal wall, through the bladder dome wall, and out the opposing side. A single plane implant was completed with 1 cm spacing with the two other catheters (Figure 1a). Catheters were secured with nylon retaining buttons (Figure 1b). A CT simulation scan confirmed placement and a plan was developed for simulated brachytherapy delivery (Figure 1c). <h3>Results</h3> Cadaveric models enable physicians to develop new brachytherapy procedures in a controlled and simulated surgical environment without affecting operative time. Physicians can gain familiarity with the procedure and practice alterations to surgical equipment, including the catheter-needle system, which may prevent complications peri- and postoperatively. The proof-of-concept trial in MITIE shows how research and training centers can serve as incubators for the development of brachytherapy techniques. With a network of these centers, experts across the country can collaborate to test new techniques on cadaveric models and accelerate developments in bladder brachytherapy. This network would provide training opportunities for physicians, especially residents, which can familiarize physicians with brachytherapy techniques, promoting their use and providing clinical data to support these techniques as a new standard of care. Currently, institutes like MITIE are limited in number, necessitating travel and coordination of attending and resident physicians' schedules. Although an expanded network of these institutes would alleviate this issue, these training centers are associated with high operating costs, including the acquisition costs and high turnover rate required of cadaveric training models. Therefore, cost may impede scalability and must be considered alongside the benefits of establishing a widespread network of research and training programs for brachytherapy. <h3>Conclusions</h3> Robotic brachytherapy is a rarely utilized, minimally invasive treatment modality for MIBC. Innovation-focused facilities with cadaveric models can provide simulated surgical environments for the research, development, and training of robotic brachytherapy techniques and applicators, accelerating the acceptance of brachytherapy as the standard of care for MIBC.

PP02 Presentation Time: 9:10 AM: Salvage Prostate Brachytherapy in Radiorecurrent Prostate Cancer: An International Delphi Consensus Study

<h3>Purpose</h3> Local recurrences after previous radiotherapy (RT) are increasingly being identified with increasing use of molecular imaging in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option for radiorecurrent prostate cancer. While supported by multiple prospective studies, limited comparative data exists to guide optimal patient selection and treatment technique. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. <h3>Materials and Methods</h3> International experts in salvage prostate BT were invited (n=34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up after salvage. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being set at ≥ 50%. <h3>Results</h3> Thirty international experts agreed to participate, and the response rates were 100% (30/30), 93.3% (28/30) and 100% (30/30) for the first, second and third rounds of the survey respectively. Consensus was achieved for 56% (18 of 32) statements. Consensus was achieved in several areas of patient selection, including: 1) A minimum of 2-3 years from initial RT and consideration of salvage BT; 2) MRI and PSMA PET should be acquired prior to salvage; 3) Both a targeted and systematic prostate biopsy should be performed; 4) Salvage BT can be considered after any initial RT technique; and 5) Any Gleason Score at recurrence could be considered for salvage. Several areas did not reach consensus and were controversial: 1) Cut off for maximum T stage and PSA at time of salvage; 2) Whether ADT should be used with salvage BT (and duration); 3) Whether it was appropriate to combine local salvage with SBRT for oligometastatic disease and 4) Whether salvage BT may be repeated more than once. More than 50% of respondents preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland salvage could be appropriate depending on the clinical situation. There was no single preferred dose fractionation for salvage prostate BT. <h3>Conclusions</h3> These findings will inform development of an international expert consensus statement for salvage prostate BT. Consensus was achieved on 56% of statements, though several controversial areas were identified. While our results highlight there is no single preferred approach for salvage BT, areas of controversy will be relevant for the design of future prospective studies and clinical trials of salvage BT.

PSOR12 Presentation Time: 12:25 PM: Technique and Preferences for Permanent LDR Prostate Brachytherapy Using Cesium-131

<h3>Purpose</h3> To identify individual technique preferences for Cesium-131 prostate implantation and determine if there is a uniform method among the brachytherapists. <h3>Methods</h3> Five experienced physicians, of the Cesium Advisory Group, using Cesium-131 monotherapy for permanent prostate brachytherapy were queried regarding their technique. A review of preferences examining variability and/or similarity for each brachytherapist was undertaken. <h3>Results</h3> Results below based on a prostate with a volume of 27cc. <h3>Conclusions</h3> Per experienced practitioners, Cesium-131 implants vary on several specifics in regards to technique. The brachytherapists are uniform in their practice to implant majority of the Cesium-131 isotope in the periphery.

GPP09 Presentation Time: 10:00 AM: Patient Specific Template-Based Hybrid Brachytherapy for Treatment of Gynecological Cancers

<h3>Purpose</h3> Interstitial vaginal and pelvic brachytherapy (BT) is standard of care in locally advanced vaginal cancers and pelvic recurrence of gynecological malignancies. An in-house automated design and 3D printing workflow for pre-plannable patient-specific cylindrical templates (PSCTs) for IC/IS HDRBT was used for 7 patients treated at BC Cancer - Kelowna. Insertion positions and dosimetry are compared for preplan and final plans, and the practicality of preplanning for IC/IS HDRBT of the vagina is discussed. This work demonstrates that patient-specific treatment techniques for gynecological brachytherapy can be implemented within the clinic at a low cost. <h3>Materials and methods</h3> Seven patients with primary or recurrent vaginal malignancies were treated with IC/IS HDRBT facilitated with a PSCT which guided the position of IC/IS needles. Patients underwent pelvic T2-MRI imaging at least 7 days before their procedure with a dummy cylinder inserted. To satisfy pre-planning goals, virtual needles orientations and dwell times were optimized and adjusted as needed until the final plan is acceptable (Figure 1). Plans were exported and 3D modeled automatically using in-house written software. PSCTs were 3D printed of PEEK, and post-processed to have a smooth final finish, as shown in Figure 1. Each needle was pushed to its final depth under abdominal ultrasound guidance after the cylinder was inserted. Post-insertion CT scans were registered to preplan MRI scans and contoured, and final plans were optimized before treatment using digitized final needle positions. Patient final plan (Figure 1) dosimetry and needle insertion statistics were calculated and compared to pre-insertion plans. <h3>Results</h3> The treated median HRCTV D90, V100, V150, V200, Bladder, Rectum, Sigmoid and Small Bowel D2cm³, were 110.8%, 96.7%, 52.8%, 28.0%, 18.0 Gy, 15.4 Gy, 11.0 Gy, and 12.9 Gy respectively. The median differences of the final treated plan (post-plan) to the preplan were 1.1%, -0.5%, 13.1%, 4.1%, 1.0 Gy, 0.8 Gy, 0.5 Gy, and -0.8 Gy respectively. The median insertion displacement of dwell positions for straight needles, curved needles, and overall was 1.3mm, 4.0mm, and 2.3mm, respectively. <h3>Conclusion</h3> 3D printed patient-specific templates for the guidance of interstitial high dose rate brachytherapy of the vagina can be used to preplan and deliver highly conformal IC/IS Vaginal HDRBT treatments. The PSCT provides a significantly easier IC/IS insertion procedure as compared to using an IC cylinder + grid or freehand needles. Patients whose HRCTV geometry was in one location extending away from the cylinder rather than wrapping around the entire vagina had improved dosimetric indices because the PSCT is geometrically constrained to only be able to fit a maximum number of needles, thus covering a wide range of directions and depths is more difficult as compared to treating a more directed region. It is possible to combine a PSCT with an IS grid template to have the advantages of both techniques. Compared to commercial IC cylinders, the PSCT is preferable, since the preplan allows for patient customization and trade-offs optimization before insertion. Since IS dwell positions are achievable through PSCTs, they achieve preferable dose to target versus OAR trade-offs. Compared to techniques using IS Grid needles, the PSCT facilitates lower interstitial needle lengths, and preferable insertion locations in the vaginal mucosa rather than through the perineum. These templates can facilitate higher quality treatment plans as compared to state of the art techniques, particularly for deep, localized, and top-of-vault lesions, improving target coverage, reducing OAR dose, reducing interstitial needle length and trauma in non-tumor tissue and improving confidence in needle insertion without intraoperative MRI or CT.

MSS05 Presentation Time: 4:05 PM: HDR Brachytherapy for Pediatric Vaginal Rhabdomyosarcoma: Two Case Reports with Long-Term Follow Up

<h3>Purpose</h3> Rhabdomyosarcomas (RMS) are the most common soft tissue tumor in children with over 400 cases diagnosed each year. Vaginal RMS is exceedingly rare, accounting for 4% of all RMS and 10% of female RMS. Outcomes are favorable with 10-year overall survival rates estimated to be over 90%. Current standard of care requires multidisciplinary approach involving chemotherapy and local therapy. To limit late effects from treatment, local therapy has advanced from radical surgeries to no local treatment in those with complete response or favoring radiation therapy for those with residual disease following chemotherapy. There is limited data on modern brachytherapy techniques for the management of vaginal RMS. Here we report two cases of pediatric vaginal RMS treated with HDR intracavitary brachytherapy at our institution and long-term follow up. <h3>Methods and Materials</h3> Following IRB approval, we identified two pediatric patients who were treated at our institution with HDR brachytherapy for RMS between 2017 and 2019 and had follow up data available. We collected demographics, presenting information, treatment data including chemotherapy, surgery if applicable, brachytherapy plans, and outcomes. <h3>Results</h3> Both patients presented at outside hospitals at the age of 2 with a prolapsing vaginal mass. Biopsies were consistent with botryoid vaginal RMS. They were referred to our institution for consideration of radiation therapy after completion of 12 weeks of VAC-based chemotherapy. Post-chemotherapy MRIs were obtained to assess extent of residual disease and a vaginal applicator was placed at the time of MRI for HDR brachytherapy planning. Both patients had good response with small areas of residual thickening along the vaginal wall. The first patient underwent exam under anesthesia, vaginal dilation and removal of visualized gross disease prior to brachytherapy. A 2.2 cm Syed obturator was used with a straight central tandem positioned at the proximal end of the obturator for central loading with 2 additional flexible catheters placed in the posterior grooves of the Syed obturator. The 3 channels allowed for coverage of the posterior and proximal vaginal disease seen on her post-chemotherapy MRI. On her last fraction, she was noted to have vaginal swelling and difficulty with inserting the Syed obturator, therefore, a 2 cm Varian single channel cylinder was used for her last fraction. For the second patient, a custom designed vaginal cylinder was made by machining a hole through a 1.3 cm vaginal dilator with a catheter inserted and affixed in the central canal. Both patients were prescribed 4.9 Gy x 6 fractions treated three times weekly with the goal of obtaining an equivalent total dose of 36 Gy with 45 Gy to the vaginal surface. The first patient was prescribed to 5mm depth and the second patient to 3mm depth based on extent of residual disease. Both patients tolerated treatment well with minimal bleeding on cylinder insertion and expected acute side effects including cystitis, dysuria and acute vaginal discomfort that resolved with sitz baths and barrier ointments. With 4 and 3 years follow up, respectively, both patients have no evidence of disease on MRI imaging and no evidence of long-term toxicities related to their brachytherapy. <h3>Conclusions</h3> Vaginal RMS is a rare cancer and thus there is limited modern experience with HDR brachytherapy as a means for local control in this patient population. Here were present two cases where devices relatively common in gynecologic brachytherapy practices can be used and customized to cover small tumors in pediatric patients. Our experience has shown that for select patients, HDR brachytherapy can be a safe, tolerable, and efficacious treatment modality for vaginal RMS.

Salvage Prostate Brachytherapy in Radiorecurrent Prostate Cancer: An International Delphi Consensus Study

<h3>Purpose/Objective(s)</h3> Local recurrences after previous radiotherapy (RT) are increasingly being identified with increasing use of molecular imaging in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option for radiorecurrent prostate cancer. While supported by multiple prospective studies, limited comparative data exists to guide optimal patient selection and treatment technique. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. <h3>Materials/Methods</h3> International experts in salvage prostate BT were invited (n=34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up after salvage. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being set at ≥ 50%. <h3>Results</h3> Thirty international experts agreed to participate, and the response rates were 100% (30/30), 93.3% (28/30) and 100% (30/30) for the first, second and third rounds of the survey respectively. Consensus was achieved for 56% (18 of 32) statements. Consensus was achieved in several areas of patient selection, including: 1) A minimum of 2-3 years from initial RT and consideration of salvage BT; 2) MRI and PSMA PET should be acquired prior to salvage; 3) Both a targeted and systematic prostate biopsy should be performed; 4) Salvage BT can be considered after any initial RT technique; and 5) Any Gleason Score at recurrence could be considered for salvage. Several areas did not reach consensus and were controversial: 1) Cut off for maximum T stage and PSA at time of salvage; 2) Whether ADT should be used with salvage BT (and duration); 3) Whether it was appropriate to combine local salvage with SBRT for oligometastatic disease and 4) Whether salvage BT may be repeated more than once. More than 50% of respondents preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland salvage could be appropriate depending on the clinical situation. There was no single preferred dose fractionation for salvage prostate BT. <h3>Conclusion</h3> These findings will inform development of an international expert consensus statement for salvage prostate BT. Consensus was achieved on 56% of statements, though several controversial areas were identified. While our results highlight there is no single preferred approach for salvage BT, areas of controversy will be relevant for the design of future prospective studies and clinical trials of salvage BT.

Cardiac Events in Breast Cancer Patients Treated with Modern Radiotherapy

<h3>Purpose/Objective(s)</h3> To characterize cardiac events in a large cohort of breast cancer patients treated with curative radiation therapy at our institution from 2006-2017. Recent reports of cardiac toxicity have primarily been limited to ischemic events. Our hypotheses were that (1) multiple classes of cardiac events would be observed, including ischemic, arrhythmia, cardiomyopathy, pericardial, and valvular events, and (2) toxicity would decrease as modern RT techniques evolved during the study period. <h3>Materials/Methods</h3> Baseline patient characteristics, comorbidities, tumor characteristics, surgical, RT, and systemic treatment were recorded. RT volumes included accelerated partial breast, whole breast, or breast/chest wall and nodal RT. Techniques included 3D-CRT, IMRT, brachytherapy, protons, with prone and deep inspiration breath hold techniques also introduced during the study period. Cardiac events were categorized by class (ischemic, arrhythmia, cardiomyopathy, pericardial, and valvular), as well as by grade (1-5) based on CTCAE and American College of Cardiology criteria. <h3>Results</h3> 3,435 breast cancer patients received adjuvant RT at our institution during this time period and were therefore included in the analysis. Median follow up for cardiac events was 96 months. Mean age at diagnosis was 57 years old and 70% of patients were postmenopausal. 71% were Caucasian, 26% African American, 2% Asian, 1% other. At baseline, 14% of patients had diabetes, 47% hypertension, 24% hyperlipidemia, and 11% had history of a cardiac event prior to treatment. Systemic therapy included endocrine therapy (66%), any chemotherapy (49%), anthracycline (25%) and Herceptin (11%). Incidence of cardiac events was 15% overall. Events by class were 4.5% cardiomyopathy, 3.6% ischemic, 7.0% arrhythmia, 1.8% pericardial, and 5.0% valvular. Patients with history of cardiac events prior to treatment had a greater risk of new events compared to those without pre-existing disease (p <0.01, RR 2.8). Incidence of Grade 1 events was 2.3%, Grade 2 was 7.2%, Grade 3 was 3.2%, and Grade 4 was 2.2%. Incidence of events by year of RT were 22% (2006-2007), 19% (2008-09), 17% (2010-11), 15% (2012-13), 12% (2014-15), and 12% (2016-17). Logistic regression found a significant decrease in cardiac events over time (p < 0.001). Median interval from RT to cardiac event was 45 months (all events), 41 mos (cardiomyopathy), 47 mos (ischemia), 53 mos (arrhythmia), and 45 mos (pericardial). <h3>Conclusion</h3> Incidence of cardiac events were overall fairly low, but not uncommon when all event classes were recorded. Incidence of events was lower in patients treated later in the study period, which may be due to introduction of further advances in RT for breast cancer patients over time. Although patients treated earlier have potential for longer follow up, the median interval to cardiac event was less than the median follow up for the cohort, so these findings will likely be observed with further follow up.

The comparison of transforming growth factor beta-1 serum levels in early-stage breast cancer patients treated with external beam whole breast irradiation plus boost versus interstitial brachytherapy accelerated partial breast irradiation

PURPOSETransforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine used as an early biomarker to develop radiation-induced fibrosis (RIF). This study aimed to compare TGF-β1 serum levels in early-stage breast cancer patients treated with whole-breast radiation therapy (WBRT) plus boost versus accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy. METHODS AND MATERIALSThis clinical trial study was conducted on 20 women with early-stage breast cancer after breast-conserving surgery candidate for adjuvant radiotherapy in Golestan hospital, Ahvaz, in 2021. In one group APBI with high-dose-rate brachytherapy (n = 10), the other group WBRT with external beam radiation plus boost (n = 10) was performed. Serum level of TGF-β1 was evaluated before radiotherapy, immediately after the end of radiotherapy and three months after the end of radiotherapy by Enzyme-linked immunosorbent assay technique (ELISA). ResultsMedian serum TGF-β1 level before radiotherapy was not significantly different between the two groups (p = 0.971). In both APBI and WBRT groups, serum TGF-β1 levels significantly decreased immediately after radiotherapy compared to before treatment (p = 0.005 and p = 0.007, respectively); But three months after radiotherapy, serum TGF-β1 levels increased significantly in the WBRT group (40.50 to 77.41 pg/mL; p = 0.017), while no significant change was observed in the APBI group (24.75 to 30.50 pg/mL; p = 0.332). ConclusionSHigher TGF-β1 values in the WBRT group after radiotherapy can be used as an early and vital biomarker in this treatment, and this data may corroborate links between TGF-beta1 and fibrosis and fibrosis rates between APBI and WBRT; It also shows the preference for using the brachytherapy technique in this group of patients. However, due to the small number of samples, definitive conclusions require further prospective studies.

High levels of health-related quality of life five years after curative treatment of prostate cancer with HDR-brachytherapy and external beam radiation

Background and purpose The aim of this cross-sectional study was to investigate long-term health-related quality of life (HRQoL) in men with prostate cancer treated 2002–2008 with external beam radiotherapy (EBRT) combined with high dose-rate brachytherapy (HDRBT), Cohort A, and to compare these data with age-adjusted normative data. In addition, differences in HRQoL following adjustments of the brachytherapy technique in 2001 were investigated by comparing Cohort A with men treated at the same clinic from 1998-2000, Cohort B. Methods and material Cohort A: 1495 men treated with EBRT 2 Gy to 50 Gy and 2 fractions of 10 Gy HDRBT at a single centre, 2002–2008, still alive at five years. As part of routine follow-up, the patients responded to the EORTC QLQ-C30 and PR-25 questionnaires. Cohort B: HRQoL data was retrieved from an earlier study from the original article. Results In Cohort A, 1046 (70%) men completed the questionnaires at five years, median age 66 years. In general, HRQoL mean scores were high and similar to Swedish age-matched normative data. Concerning disease-specific HRQoL, low levels of bowel and urinary problems were reported, in contrast to a substantial effect on sexual functioning. ‘No’ or ‘A little’ problems with faecal incontinence and urinary incontinence were reported by 98% and 93% of patients, respectively. The corresponding figure for sexual functioning was 39%. A difference in the frequency of nocturia in favour of Cohort A was the only statistically significant difference between Cohort A and B found in general and disease-specific HRQOL (p = 0.03), despite modifications in the brachytherapy procedure introduced in 2001. Conclusion Long-term general HRQoL was rated high and comparable to an aged-matched reference population five years after treatment with combined radiotherapy. Disease-specific HRQoL was still affected, foremost in the sexual domain.

Applying 3D-Printed Templates in High-Dose-Rate Brachytherapy for Cervix Cancer: Simplified Needle Insertion for Optimized Dosimetry

In cervical cancer brachytherapy, adding interstitial needles to intracavitary applicators can enhance dosimetry by improving target coverage while limiting normal tissue dose. However, its use is limited to a subset of practitioners with appropriate technical skill. We designed tandem anchored radially guiding interstitial templates (TARGITs) with a 3-dimensional (3D) printing workflow to optimize needle placement and facilitate greater ease-of-use of intracavitary/interstitial (IC/IS) technique. This study compared dosimetry and procedure characteristics between tandem and ovoid (T&O) implants using TARGIT technique versus non-TARGIT technique. This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive radiation treatment for cervical cancer between February 2017 and January 2021. TARGIT technique was implemented from November 2019 onwards; all prior procedures involved non-TARGIT technique using a no needle or freehand needle approach. Target coverage, dose to organs at risk, and procedure times were evaluated and compared between TARGIT technique and non-TARGIT technique. The cohort included 70 patients with cervical cancer who underwent 302 T&O procedures: 68 (23%) with TARGIT technique and 234 (77%) with non-TARGIT technique, which included 133 no needle and 101 freehand needle implants. TARGIT implants involved longer average procedure times (+6.3 minutes, P < .0001). TARGIT implants achieved a higher mean high-risk clinical target volume V100% than non-TARGIT implants (+4.4%, P = .001), including for large tumors 30 cm3 or greater (+8.1%, P = .002). Average D90 was 4.6 Gy higher and average D98 was 3.2 Gy higher for TARGIT technique compared with non-TARGIT technique (P = .006 and P = .02). Total treatment doses to rectum, bowel, and bladder were not significantly different for TARGIT versus non-TARGIT technique. The 3D-printed TARGIT approach to T&O brachytherapy achieved greater tumor coverage while sparing normal tissues, particularly for large tumor volumes, with only a slight increase in average procedure time. TARGIT represents a creative technological solution for increasing accessibility of advanced IC/IS brachytherapy technique for cervical cancer definitive radiation treatment.

MRI-Guided Intraluminal HDR Brachytherapy for Inoperable Malignant Biliary Tract Obstruction

Aim: Malignant biliary tract obstruction (MBTO) leads to abdominal pain, jaundice, poor quality of life and portends a poor prognosis. Management of MBTO is a significant therapeutic challenge given that treatment with chemotherapy or radiotherapy has limited utility and percutaneous biliary drainage or stent insertion provides only transient symptomatic relief. Intraluminal HDR brachytherapy via catheters inserted percutaneously at the time of stent insertion can be effective in the management of inoperable MBTO. Here, we describe the workflow developed within our department for simulation and treatment using an intraluminal brachytherapy technique. Process: Delivery of bile duct brachytherapy requires the participation of multiple disciplines including interventional radiology (IR), medical physics, radiation oncology (RO) and radiation therapy with careful coordination of numerous tasks. A drain/stent and 1-2 treatment catheters are inserted into the patient's bile ducts by IR before the CT and MR simulation (sim). During the CT sim, multiple surview and low dose helical scans are acquired to verify the treatment catheter position and adjustments are made by the RO as needed. Once the position is finalized, a planning CT scan is done with IV contrast and the patient in voluntary breath hold. Then, the CT and MR sim images are fused. The CT is used to digitize the brachytherapy source path, while the MR is used for target and organs at risk delineation. Treatment is delivered 1-2 days after sim, with 15-25 Gy in 3-5 fractions using an Ir-192 HDR source. Radiographs are taken to confirm catheter position prior to each treatment. Benefits/Challenges: Brachytherapy can be used to treat the tumor at the same time as placement of a stent/drain, thus providing both symptom management and disease control. Although the patient is admitted for the IR procedure, the actual brachytherapy treatment is done on an outpatient basis with no anesthesia, thus treatment does not require significant time or resources in the brachytherapy suite. Patients often present with biliary obstruction emergently and stent/drain placement is booked urgently in IR with little notice to the radiotherapy department. The tight time line makes it difficult to facilitate communication between the multidisciplinary team, prepare staff, assemble supplies, and coordinate subsequent appointments. The CT sim process continues to evolve as new issues are identified with each patient. Variations in catheter/stent placement is a potential challenge and 2/8 patients have required reinsertion of angio-sheath by IR after problems were discovered during the CT sim. MR sim is not always possible depending on nature of inserted material (i.e. metallic stent or drainage sheath). Treatment catheters must be secured in place and covered with a dressing between appointments to prevent damage, change in position or obstruction. Patient education and cooperation is crucial to ensure proper care. Impact/Outcomes: In April 2021, our institution became the first in Canada to offer MRI-guided brachytherapy treatment for patients with inoperable MBTO. As of Jan 2022, 8 patients have been treated using this protocol. With each subsequent case, the time required for treatment delivery has decreased from 1 hour to 30 minutes per fraction and sim processes optimized. This treatment option has potential to improve the quality of life in patients with minimal therapeutic options.

Evaluation of Radiation Oncologist and Trainee Opinions on Residency Expansion, Possible Actions, and Training Program Accreditation Changes in the United States

The objective of this study was to sample the opinions of radiation oncologists and trainees in the United States regarding residency expansion, what action(s) should be taken to limit residency supply, if any, and the proposed Accreditation Council for Graduate Medical Education (ACGME) changes. An online survey was distributed to 1048 attending radiation oncologists by e-mail and approximately 800 residents through their program coordinators. The survey asked respondents to rank how strongly they agreed with certain statements regarding residency supply, possible solutions to address any perceived oversupply, and the proposed ACGME changes on a 1-to-10 disagreement-to-agreement scale. The 16% response rate yielded 294 responses for analysis. Of the respondents, 90 (30%) were residents, and 204 (70%) were attendings, of whom 117 (57%) were academic and 87 (43%) were nonacademic. Eighty-six percent agreed that there is a residency oversupply issue, and 91% agreed that actions should be taken to limit residency expansion. On χ2 test, residents and attendings were similarly likely to agree that there is a residency oversupply issue (93% and 89%, P=.27), although residents were more likely to agree that this oversupply should be acted upon compared with attendings (100% and 88%, P < .01). Regarding possible solutions, respondents were most likely to agree that further expansion should be limited (90%), program requirements should be made more stringent (76%), and the use of the Supplemental Offer and Acceptance Program should be limited (69%). Proposed ACGME changes that respondents were most likely to agree with included requiring that programs have modern image guidance, stereotactic radiation therapy, and brachytherapy techniques (98%) and have 4+ faculty members and maintain a faculty-to-resident ratio of >1.5:1 (86%). Case log minimums most supported to be increased were 4 uterus (65%) and 11 postmastectomy breast (61%) simulations. The majority of respondents agree that there is a residency oversupply issue and that actions should be taken to limit residency expansion and make program requirements more stringent.

Quality of Life among Survivors of Locally Advanced Cervical Cancer Treated with Definitive Chemoradiotherapy in a Decade of Transition

Introduction The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiotherapy (CRT). External beam radiotherapy (EBRT) and brachytherapy (BRT) advances in the last decade have resulted in improved local control and survival. There is a lack of data on quality of life (QoL) among survivors.Objective This systematic review aimed to synthesize published data on QoL among LACC survivors treated with CRT and determine clinical factors of QoL.Methods Systematic literature search was conducted in PubMed, EBSCO, and ScienceDirect for relevant articles published in 2010 to 2020. Eligible studies on LACC survivors aged 18 years and above, who reported QoL after CRT, were included. Screening and data extraction were done by two pairs of independent reviewers.Results Five cohort studies, three cross sectional studies, and one clinical trial were included. Reported temporal evolution of QoL varied: two studies reported improvement of overall QoL, while four reported worsening of symptoms. Gastrointestinal, genitourinary, sexual, and psychosocial domains showed significant impairment. Age, stage, and baseline distress and physical condition were clinical determinants of body image, sexual activity, menopausal symptoms, distress, and dyspnea. Peripheral neuropathy, lymphedema, and dyspnea were reported, while grade 3 to 4 gastrointestinal, genitourinary, and musculoskeletal toxicities were rare.Conclusion Use of advanced EBRT and BRT techniques is associated with improving QoL in the first 3 years from treatment completion. Gastrointestinal, genitourinary, sexual, and psychosocial functions remain impaired on the long-term. Other late toxicities worth noting include peripheral neuropathy, lower limb edema, and insufficiency fractures.

Feasibility of electronic brachytherapy in cervix cancer–A dosimetric comparison of different brachytherapy techniques

This study analyzes cases in which electronic brachytherapy (eBT) led to acceptable treatment plans in cervical cancer. Findings were compared with dosimetry values obtained in 192Ir-based treatments according to the high-risk clinical target volume (HR-CTV) and the disease stage. We retrospectively analyzed 48 patients with cervical cancer from two centers. The patients were treated with 192Ir based on MRI. It was possible to use interstitial needles via an Utrecht-type applicator. Dosimetry was simulated using eBT and the parameters D90 and D98 (HR-CTV) and D2cc, D1cc, and D0.1cc (bladder, rectum, and sigmoid colon) were evaluated. The Mann-Whitney U test was used for comparison. The overall cohort of patients was analyzed, as were the sub-cohorts based on stage (FIGO stages I+IIA, IIB and III-IV). Finally, the dosimetry of the eBT plans was evaluated, and the plans obtained were classified as "good", "acceptable", or "poor". Statistically significant differences were found between the eBT and 192Ir plans for D98 (HR-CTV), D1cc and D0.1cc (bladder), and D1cc and D0.1cc (sigmoid colon). A total of 31 cases (64.6%) were considered good, seven (14.6%) were considered acceptable, and 10 (20.8%) were considered poor. For volumes <30 cc, all the plans were good or acceptable; for volumes >30 cc, 54.3% were good, and 71.4% were good or acceptable. By stage, eBT plans for patients with stage IB-IIA disease were good in 100%, whereas those for patients with stage IIB were good in 70.6% and III-IV disease were good in 50%. eBT provides appropriate dosimetry for treatment of cervical cancer in selected cases.

Narrative Review of High-Dose-Rate Interstitial Brachytherapy in Primary or Secondary Liver Tumors.

The optimal management of intrahepatic malignancies involves a multidisciplinary approach. Although surgical resection has been considered the only curative approach, the use of several minimally invasive ablative techniques has dramatically increased the last two decades, mainly due to the fact that they provide similar oncological results with significantly decreased morbidity. Among these modalities, interstitial liver brachytherapy, probably the most flexible liver ablative method, with excellent clinical data on its safety and effectiveness, is frequently not even mentioned as an option in the current peer reviewed literature and guidelines. Brachytherapy is a type of radiotherapy utilizing radionuclides that are directly inserted into the tumor. Compared to external beam radiation therapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time, with the advantage of a rapid dose fall-off, that allows for sparing of adjacent healthy tissue. For numerous malignancies such as skin, gynecological, breast, prostate, head and neck, bladder, liver and soft-tissue tumors, brachytherapy as a monotherapy or combined with external beam radiation therapy, has become a standard treatment for many decades. This review article aims to describe the high-dose-rate liver brachytherapy technique, its selection criteria, present its advantages and disadvantages, as well as the available clinical data, in order to help physicians to explore and hopefully introduce liver brachytherapy into their clinical routine.

Prognostic Implications of Uterine Cervical Cancer Regression During Chemoradiation Evaluated by the T-Score in the Multicenter EMBRACE I Study

A simple scoring system (T-score, TS) for integrating findings from clinical examination and magnetic resonance imaging (MRI) of the primary tumor at diagnosis has shown strong prognostic capability for predicting local control and survival in locally advanced cervical cancer treated with chemoradiation and MRI-guided brachytherapy (BT). The aim was to validate the performance of TS using the multicenter EMBRACE I study and to evaluate the prognostic implications of TS regression obtained during initial chemoradiation. EMBRACE I recruited 1416 patients, of whom 1318 were available for TS. Patients were treated with chemoradiation followed by MRI-guided BT. A ranked ordinal scale of 0 to 3 points was used to assess 8 anatomic locations typical for local invasion of cervical cancer. TS was calculated separately at diagnosis (TSD) and at BT (TSBT) by the sum of points obtained from the 8 locations at the 2 occasions. Median TSD and TSBT was 5 and 4, respectively. TS regression was observed in 71% and was an explanatory variable for BT technique (intracavitary vs intracavitary/interstitial) and major dose-volume histogram parameters for BT, such as high-risk clinical target (CTVHR), CTVHR D90 (minimal dose to 90% of the target volume), D2cm3 bladder (minimal dose to the most exposed 2 cm3 of the bladder), and D2cm3 rectum. TS regression (TSBT≤5) was associated with improved local control and survival and with less morbidity compared with patients with TSBT remaining high (>5) despite initial chemoradiation. TS regression was significant in multivariate analysis for both local control and survival when analyzed in consort with already established prognostic parameters related to the patient, disease, and treatment. TS was validated in a multicenter setting and proven to be a strong multidisciplinary platform for integration of clinical findings and imaging with the ability to quantitate local tumor regression and its prognostic implications regarding BT technique, dose-volume histogram parameters, local control, survival, and morbidity.

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

Simple SummaryThere are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We analysed decision criteria influencing the selection for adjuvant radiotherapy among European radiation oncology experts. For this, GEC-ESTRO provided 19 European radiation oncology experts on gynaecological brachytherapy for decision-making analyses. The manuscript presents patterns in decision-making among these experts and demonstrates areas of consensus/discrepancies. We also analysed dose prescription and techniques of brachytherapy. This analysis is of special value as the objective approach enabled us to obtain an unbiased description of decision-making among the specialists (the study was not aimed to create or enforce a consensus). The manuscript provides valuable insight into clinical decision-making with a high impact on treatment selection, as expected differences between experts were observed. With this manuscript we are able to visualize and quantify these. This information is relevant for interdisciplinary discussions.Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1–2 LVSI-negative disease. For 74–84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. Conclusions: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1–2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.