Image-guided High-dose-rate Brachytherapy Research Articles

Image-Guided High-Dose-Rate Brachytherapy for Definitive Management of Primary Vaginal Cancer: A Single Institutional Experience

To assess the safety and efficacy of image-guided high-dose-rate brachytherapy (IGBT) alone or in combination with external beam radiation therapy (EBRT) for the treatment of vaginal cancers. The study analyzed patients diagnosed with primary vaginal cancers from 2004 to 2021 who received definitive radiotherapy at a single institution. Interstitial implants were performed using a freehand technique and transvaginal or transrectal-ultrasound for imaging guidance. IGBT was planned using inverse planning simulated annealing (IPSA) software. Data collected and analyzed included patient and tumor characteristics, dose and fractionation, and treatment outcomes. Complications were assessed using CTCAEv4 scores, and descriptive and survival analyses were performed using R-studio. Sixty-six patients met inclusion criteria. Patients were staged as I (14), II (23), III (19), and IV (10) based on revised FIGO 2018 staging. 47 (72%) had squamous cell carcinoma histology, and median age was 65 years. The most common regimen was 45 Gy in 25 fractions of EBRT followed by IGBT boost of 18 Gy in 3 fractions with 1 implant (n = 40). For melanoma, an IGBT boost of 19 Gy in 2 fractions with a single implant was used (n = 7). For IGBT monotherapy, the most common regimen was 36 Gy in 6 fractions delivered over 2 implants (n = 3). 41 (66%) of the patients received systemic therapy. Local failures occurred in 8 (12%) patients, while 8 (12%) developed distant metastases. Median overall survival was 64.7 months. Overall survival was 64.3% (95% CI 51.9-79.7%) at 3 years, and 50.9% (95% CI 35.7-72.5%) at 5 years. Grade 3 or 4 toxicities were reported in 4 (6%) patients including vaginal fistula (n = 3) and urethral stricture (n = 1). The results suggest that utilizing IGBT for freehand interstitial implants in combination with EBRT is a safe and effective primary treatment for vaginal cancer, with durable local control and low toxicity. Further research is needed to establish multi-institutional practice patterns and recommendations.

A Pilot Study of Moderately Hypo-Fractionated Whole Pelvic Radiotherapy with Concurrent Chemotherapy and Image-Guided High Dose Rate Brachytherapy for Locally Advanced Cervical Carcinoma

<h3>Purpose/Objective(s)</h3> The standard treatment of locally advanced cervical carcinoma (LACC) is whole pelvic radiotherapy (WPRT) with concurrent cisplatin and intracavitary brachytherapy (ICBT). EBRT is typically delivered to a dose of 45-50.4 Gray at 1.8-2 Gray per fraction. While moderate hypofractionation (H-EBRT) have been practiced, prospective evidence is limited. We evaluated the role of H-EBRT in terms of toxicities and clinical outcome in LACC. <h3>Materials/Methods</h3> 50 patients of squamous cell carcinoma of cervix were recruited in this prospective interventional trial between December 2018-December 2021 (CTRI/2018/11/016415). Patients were treated with WPRT 40 Gray in 16 fractions over 3.5 weeks with boost to pelvic lymph nodes 10 Gray in 4 fractions with 3-DCRT and concurrent cisplatin weekly 40 mg/m² followed by image guided high dose rate ICBT 7Gray in 4 fractions. Cumulative EQD2 (equivalent dose at 2 Gray per fraction) for high-risk clinical target volume and organs at risk were derived. Acute and late toxicities were recorded as per CTCAE version 4.0 and RTOG criteria respectively. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan Meier method <h3>Results</h3> Patient characteristics are summarized in Table 1. All patients completed intended course of treatment. 6 patients received nodal boost. Median number of concurrent chemotherapy cycles were 4 (range 3-5). Median (range) cumulative EQD2 for HR-CTV, rectum, bladder and sigmoid were 80.15 (68-104.9), 65.91 (51.1-75.18), 82.05 (58.58-94.96) and 55.96 (46.5-86.76) respectively. Acute ≥ Grade 2 and ≥ Grade 3 gastrointestinal (GI), genitourinary (GU), anemia, leucopenia, and thrombocytopenia were seen in 20 (40%) and 10 (20%), 5 (10%) and 3 (6%), 10 (20%) and 3 (6%), 15 (30%), and 4 (8%), 6 (12%), and 3 (6%), respectively. Late grade 2 and grade 3 GI toxicity was seen in 6 (12%) and 2 (4%) patients and late grade 2 GU toxicity were observed in 3 (6%) patients. Three patients had developed recurrence at the time of last follow-up and all three died from disease. Estimated 2- and 3-year overall survival was 94.9% and 90.6% respectively and 2- and 3-year DFS was 92.7% and 92.7% respectively. <h3>Conclusion</h3> Moderately hypo-fractionated WPRT is well tolerated with acceptable acute and late toxicity profiles and yielded excellent clinical outcome. This schedule would lead to lesser overall treatment time, increased compliance and also be resource sparing and cost effective. Longer follow up would yield more data on late toxicity. Randomized study comparing this schedule with conventional fractionated schedule is warranted.

Bevacizumab increases late toxicity in re-irradiation with image-guided high-dose-rate brachytherapy for gynecologic malignancies.

IntroductionPatients with recurrent gynecologic malignancies having had pelvic irradiation, generally have limited salvage options. This study investigated patients with gynecologic malignancies, who had a history of pelvic irradiation and received salvage re-irradiation using image-guided high-dose-rate brachytherapy (IG-HDR-BT).Material and methodsPatients with gynecologic malignancies, who had a history of previous irradiation and received re-irradiation using IG-HDR-BT for disease recurrences from June 2014 to March 2020 were included in this study.ResultsA total of 37 patients were included in this retrospective analysis. Primary tumor was uterine cervical cancer in 31 patients, endometrial cancer in 5 patients, and vaginal cancer in 1 patient. Median follow-up period of patients who were alive at the time of analysis was 15.4 months (range, 4.1-61.4 months). Two-year overall survival, progression-free survival, and local control were 68.9%, 49.3%, and 67.5%, respectively. Severe late toxicities ≥ grade 3, which were related to re-irradiation, were observed in 9 patients (24.3%). Usage of bevacizumab in the entire course of treatment was associated with development of late ≥ grade 3 fistula formation, bowel perforation, or vaginal ulcer (50% vs. 6.9%, p = 0.013). Tumor size ≥ 2.5 cm was associated with development of late ≥ grade 3 of rectum, bladder, or vaginal toxicities (0% vs. 28%, p = 0.047).ConclusionsIf the recurrent disease was found in small size and there was no history of bevacizumab usage, re-irradiation with IG-HDR-BT could be considered, even in patients with a previous history of pelvic irradiation.

Using Endoscopic Optical Coherence Tomography to Detect and Treat Early-Stage Pancreatic Cancers.

We developed a novel technology capable of detecting early-stage pancreatic cancers using high-resolution three-dimensional endoscopic optical coherence tomography (Endo-OCT), and treating them using high dose rate brachytherapy (HDR) under the Endo-OCT image guidance. This technology integrates our custom-built ultra-high resolution endoscopic three-dimensional OCT diagnostic imaging device with a commercial high dose rate brachytherapy system (HDR), resulting in a compact, portable, easy-to-operate, and low-cost Endo-OCT image-guided high dose rate brachytherapy (OCT-IGHDR) system. The system has the dual functions of diagnosis and treatment that can precisely detect and measure the location and size of the early-stage pancreatic cancer or premalignant lesions and then treat them from the inside of the pancreatic duct with an accurate and focused dose while greatly reducing the radiation toxicity to the neighboring tissues and organs. This minimally-invasive treatment technology could avoid the potential complications from surgery and reduces the high operation cost. This technology could also be applied to treat diseases of the esophagus, rectum, bronchus, and other aerodigestive organs that are suitable for use with an endoscopic device. In this article, we describe the concept of this technology and the preliminary experiments that could demonstrate the concept by using this homemade Endo-OCT machine to image the pancreatic duct for diagnosis of early-stage pancreatic cancer or premalignant lesions and to perform Endo-OCT image-guided brachytherapy.

Image guided high-dose-rate brachytherapy versus volumetric modulated arc therapy for head and neck cancer: A comparative analysis of dosimetry for target volume and organs at risk.

BackgroundThe aim of the study was to present dosimetric comparison of image guided high-dose-rate brachytherapy (IGBT) with volumetric modulated arc therapy (VMAT) for head and neck cancer regarding conformity of dose distribution to planning target volume (PTV) and doses to organs at risk (OARs).Patients and methodsThirty-eight consecutive patients with T1-4 mobile tongue, floor of mouth and base of tongue cancer treated with IGBT were selected. For these patients additional VMAT treatment plans were also prepared using identical computed tomography data. OARs and PTV related parameters (e.g. V98, D0.1cm3, Dmean, etc.) were compared.ResultsMean V98 of the PTV was 90.2% vs. 90.4% (p > 0.05) for IGBT and VMAT, respectively. Mean D0.1cm3 to the mandible was 77.0% vs. 85.4% (p < 0.05). Dmean to ipsilateral and contralateral parotid glands was 4.6% vs. 4.6% and 3.0% vs. 3.9% (p > 0.05). Dmean to ipsilateral and contralateral submandibular glands was 16.4% vs. 21.9% (p > 0.05) and 8.2% vs. 16.9% (p < 0.05), respectively.ConclusionsBoth techniques showed excellent target coverage. With IGBT dose to normal tissues was lower than with VMAT. The results prove the superiority of IGBT in the protection of OARs and the important role of this invasive method in the era of new external beam techniques.

SU-E-T-310: Dosimetric Comparison of Tandem and Ovoid (TO) Vs. Tandem and Ring (TR) Applicators in High-Dose Rate (HDR) Brachytherapy (BT) for the Treatment of Locally-Advanced Cervical-Cancer

Purpose: To investigate the dosimetric differences associated with the use of TO or TR applicators for cervical-cancer HDR BT. Methods: The records of all cervical-cancer patients treated with image-guided HDR BT in 2013 were reviewed. Image-based planning based on isodose line and DVH metrics inspections was performed following the GEC-ESTRO recommendations. CTV volume, CTV D90, and rectum, bladder and sigmoid D2cc were collected as % of the prescription dose (80Gy EQD2). Patients receiving both TO and TR were identified and plans were compared (paired analysis). A Student T-test was used to evaluate statistical significance (p ≤ 0.05). Results: Twenty-eight patients were identified (20 TR only, 4 TO only, 4 TO and TR), associated with 116 plans (109 TR, 7 TO). Overall metrics: CTV volume, 26.5±10.4 cm3 (TR) and 39.1±14.0 cm3 (TO, p < 0.01); CTV D90, 126±28% (TR) and 110±15% (TO, p = 0.15); rectum D2cc, 56±11% (TR) and 58±19% (TO, p = 0.91); bladder D2cc, 74±20% (TR) and 88±19% (TO, p = 0.09); sigmoid D2cc, 52±17% (TR) and 49±20% (TO, p = 0.63). The paired analysis results were: CTV volume, 37.3±11.9 cm3 (TR) and 51.0±23.1 cm3 (TO, p = 0.23); CTV D90, 111±12% (TR) and 101±17% (TO, p = 0.50); rectum D2cc, 56±12% (TR) and 53±16% (TO, p = 0.71); bladder D2cc, 73±14% (TR) and 90±20% (TO, p = 0.22); sigmoid D2cc, 59±10% (TR) and 59±22% (TO, p = 0.98). Conclusion: TR and TO were both used with good dosimetric results. TO were used for patients with larger CTV volumes than TR, although paired analysis suggest that tissue distortion and contouring bias may partially explain this Result. CTV D90 on average > 80 Gy EQD2 were achieved in both groups despite the different CTV volume. Higher bladder D2cc for TO than TR was observed.

Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

PurposeTo determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies.Material and methodsThis retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival.ResultsThe median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities.ConclusionsWe demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC.

Pseudo Central-Catheter Method for Asymmetrical Vaginal Prescription with Multi-Channel Cylindrical Applicators in Image-Guided High Dose-Rate Brachytherapy

Multi-channel cylindrical applicators for high dose-rate (HDR) brachytherapy are utilized mainly for special gynecology cases often involving image-guidance high dose-rate (IG-HDR or IGBT) brachytherapy. In these cases, doses are prescribed to partial vaginal wall/depth where the disease is indicated by an MRI study scanned on the same day. These novel IG-HDR procedures are logistical challenges comparing to typical HDR out-patient treatments due to the complexity of planning for asymmetrical prescriptions as well as the extension of the whole procedure. Indeed the main advantages of HDR over LDR brachytherapy would be significantly weaken unless the IG-HDR procedures become more efficient in time, thus timely treatment planning becomes crucial. Based on our clinical experience, we propose the pseudo central-catheter method to reduce errors, to minimize uncertainty and to ensure efficiency. In this method, the central hollow path of the multi-channel cylindrical applicator is digitized into a pseudo catheter similar to other active catheters, and the asymmetrical prescription points could be generated corresponding to the pseudo dwelling points in the pseudo central-catheter. The pseudo dwelling points are later deleted after generating the prescription point arrays. This method is robust with minimal chance of errors or uncertainties, and demonstrates high efficiency with much less chance of uncertainty, which is significant for IG-HDR brachytherapy procedures utilizing multi-channel applicators.

The implementation of a PDR 3D-guided gynaecological brachytherapy service in a UK centre

AbstractBackgroundDue to the discontinuation of the widely used low-dose rate (LDR) Caesium afterloader units, many centres in the past 10 years have moved from LDR Selectron treatments to Iridium 192 afterloaders. While the majority of UK centres have opted for high-dose rate (HDR) units, the Christie have invested in two pulsed dose rate (PDR) afterloaders alongside a move to full 3D-planned gynaecological brachytherapy.PurposeTo share the experience and learning curve involved in the implementation of a 3D-guided PDR brachytherapy service.MethodsThe specific logistical and practical challenges of implementing a PDR service are discussed alongside the more general challenges of implementing 3D-guided magnetic resonance (MR) based brachytherapy. A multidisciplinary approach was undertaken to streamline the patient pathway and give all disciplines a forum to discuss service improvements and resolve problems.ConclusionsThe lessons learned throughout this experience can inform the decisions of departments that may wish to implement a PDR service or indeed a 3D image-guided HDR brachytherapy service in the future. The focus on the utilisation of lean principles to the patient pathway, improved multidisciplinary working and enhancing service efficiency is of interest to all centres.

Dosimetric Analysis of 3D Image-Guided HDR Brachytherapy Planning for the Treatment of Cervical Cancer: Is Point A-Based Dose Prescription Still Valid in Image-Guided Brachytherapy?

The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate (HDR) brachytherapy planning for cervical cancer treatment and compare dose coverage of high-risk clinical target volume (HRCTV) to traditional Point A dose. Thirty-two patients with stage IA2–IIIB cervical cancer were treated using computed tomography/magnetic resonance imaging–based image-guided HDR brachytherapy (IGBT). Brachytherapy dose prescription was 5.0–6.0 Gy per fraction for a total 5 fractions. The HRCTV and organs at risk (OARs) were delineated following the GYN GEC/ESTRO guidelines. Total doses for HRCTV, OARs, Point A, and Point T from external beam radiotherapy and brachytherapy were summated and normalized to a biologically equivalent dose of 2 Gy per fraction (EQD2). The total planned D90 for HRCTV was 80–85 Gy, whereas the dose to 2 mL of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy, and 75 Gy, respectively. The mean D90 and its standard deviation for HRCTV was 83.2 ± 4.3 Gy. This is significantly higher ( p < 0.0001) than the mean value of the dose to Point A (78.6 ± 4.4 Gy). The dose levels of the OARs were within acceptable limits for most patients. The mean dose to 2 mL of bladder was 78.0 ± 6.2 Gy, whereas the mean dose to rectum and sigmoid were 57.2 ± 4.4 Gy and 66.9 ± 6.1 Gy, respectively. Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients. Dose to Point A was found to be significantly lower than the D90 for HRCTV calculated using the image-based technique. Paradigm shift from 2D point dose dosimetry to IGBT in HDR cervical cancer treatment needs advanced concept of evaluation in dosimetry with clinical outcome data about whether this approach improves local control and/or decreases toxicities.