Clinical and dosimetric correlation in terms of treatment response, bladder and rectal toxicities in cervical cancer patients treated with cobalt 60 high dose rate brachytherapy.

Background: High dose rate (HDR) image-guided brachytherapy with Cobalt-60 isotope is a relatively recent approach. The aim of the study is to evaluate the clinical and dosimetric parameters in terms of tumour response, bladder, and rectal toxicity in patients undergoing Co-60 HDR brachytherapy. Materials and Method: All patients were initially treated with chemoradiation (CT-RT) at our center or other referral centers with external beam radiation therapy (EBRT) for a dose of 45 Gy-60 Gy at 1.8-2Gy/fraction (including nodal boost) with concomitant chemotherapy with either cisplatin or carboplatin. Patients were then scheduled for brachytherapy within 1 week after completion of CT-RT and are assessed by local examination. Depending on local examination parameters at the time of brachytherapy they were eligible either for intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT). Results: The complete response (CR) observed in stage I, II, III, IVA were 60%, 79.4%, 86% and 76.2% respectively. Complete response was seen in patients with mean EQD2 of 78.67 Gy10, 83.33 Gy10, 84.23 Gy10, 85.63 Gy10 in stages I, II, III, IVA respectively. 79.2% of cisplatin-treated patients and 87.5% of carboplatin-treated patients had a complete response indicating that patients treated with either chemotherapy had similar response rates. Conclusions: According to results obtained from the study we conclude by saying that higher rates of complete response to treatment in cervical cancer is seen in patients with shorter overall treatment time (OTT), shorter interval between end of definitive CT-RT and beginning of brachytherapy and squamous cell histology. The study also noted the trend of increasing mean EQD2 to tumor with increasing stage for achieving complete response. Higher acute bladder and rectal toxicity is seen in patients who received EQD2 of ¿70-90Gy3 and ¿70Gy3 respectively. The study findings suggest that the clinical outcomes and the toxicities are clinically comparable with other radioisotope based HDR brachytherapy treatment.

Robotic MR-guided high dose rate brachytherapy needle implantation in the prostate (ROBiNSon)-a proof-of-concept study.

Objective.A robotic needle implant device for MR-guided high-dose-rate (HDR) prostate brachytherapy was developed. This study aimed to assess the feasibility and spatial accuracy of HDR brachytherapy using the robotic device, for a single intraprostatic target point.Approach.Five patients were treated from November 2019-June 2022 with the robot. The robot fits a 1.5 T MR scanner and the needle can be shifted and angulated. An intraprocedural MR scan was fused with the diagnostic MR and one preplanned needle position was selected for robotic insertion. The needle entry point and angles were set for a needle tip target point within the intraprostatic target volume. The needle was tapped stepwise towards the target point pneumatically. Final needle position was verified with MR, followed by plan optimization and dose delivery. Any remaining planned needles were inserted manually. Needle tip to geometrical target error (NTG-error) was defined as the deviation of the actual tip position relative to the predefined geometric target point, using MR-coordinates. Needle tip to treatment target error (NTT-error) was defined as the deviation of the actual tip position relative to the treatment target point, using fused MR-images pre- and post-needle implantation taking into account prostate deformation. Difference between NTT-error and NTG-error and fiducial marker shifts indicated prostate movement. For determining prostate deformation, the Jaccard index and prostate volumes were assessed.Main results.The robotic device was able to tap the needle to the planned depth for all patients. Mean robotic procedure duration was 142 min. NTG-error was 3.2 (range 1.1-6.7) mm and NTT-error 4.5 (range 2.6-9.6) mm. Marker displacements were smaller than 3 mm. No treatment-related acute toxicity was reported. Feasibility of needle placement within the prostate was considered adequate.Significance.MR-guided robotic needle insertion is feasible with a mean geometric accuracy of 3.2 mm and <3 mm prostate movement.

Engineering single-cycle MeV vector for CRISPR-Cas9 gene editing.

CRISPR-Cas9-mediated gene editing has vast applications in basic and clinical research and is a promising tool for several disorders. Our lab previously developed a non-integrating RNA virus, measles virus (MeV), as a single-cycle reprogramming vector by replacing the viral attachment protein with the reprogramming factors for induced pluripotent stem cell generation. Encouraged by the MeV reprogramming vector efficiency, in this study, we develop a single-cycle MeV vector to deliver the gRNA(s) and Cas9 nuclease to human cells for efficient gene editing. We show that the MeV vector achieved on-target gene editing of the reporter (mCherry) and endogenous genes (HBB and FANCD1) in human cells. Additionally, the MeV vector achieved precise knock-in via homology-directed repair using a single-stranded oligonucleotide donor. The MeV vector is a new and flexible platform for gene knock-out and knock-in modifications in human cells, capable of incorporating new technologies as they are developed.

Targeted knock-in of NCF1 cDNA into the NCF2 locus leads to myeloid phenotypic correction of p47 phox -deficient chronic granulomatous disease.

p47 phox -deficient chronic granulomatous disease (p47-CGD) is a primary immunodeficiency caused by mutations in the neutrophil cytosolic factor 1 (NCF1) gene, resulting in defective NADPH oxidase function in phagocytes. Due to its complex genomic context, the NCF1 locus is not suited for safe gene editing with current genome editing technologies. Therefore, we developed a targeted NCF1 coding sequence knock-in by CRISPR-Cas9 ribonucleoprotein and viral vector template delivery, to restore p47 phox expression under the control of the endogenous NCF2 locus. NCF2 encodes for p67 phox , an NADPH oxidase subunit that closely interacts with p47 phox and is predominantly expressed in myeloid cells. This approach restored p47 phox expression and NADPH oxidase function in p47-CGD patient hematopoietic stem and progenitor cells (HSPCs) and in p47 phox -deficient mouse HSPCs, with the transgene expression following a myeloid differentiation pattern. Adeno-associated viral vectors performed favorably over integration-deficient lentiviral vectors for template delivery, with fewer off-target integrations and higher correction efficacy in HSPCs. Such myeloid-directed gene editing is promising for clinical CGD gene therapy, as it leads to the co-expression of p47 phox and p67 phox , ensuring spatiotemporal and near-physiological transgene expression in myeloid cells.

Identification and Validation of New DNA-PKcs Inhibitors through High-Throughput Virtual Screening and Experimental Verification.

DNA-PKcs is a crucial protein target involved in DNA repair and response pathways, with its abnormal activity closely associated with the occurrence and progression of various cancers. In this study, we employed a deep learning-based screening and molecular dynamics (MD) simulation-based pipeline, identifying eight candidates for DNA-PKcs targets. Subsequent experiments revealed the effective inhibition of DNA-PKcs-mediated cell proliferation by three small molecules (5025-0002, M769-1095, and V008-1080). These molecules exhibited anticancer activity with IC50 (inhibitory concentration at 50%) values of 152.6 µM, 30.71 µM, and 74.84 µM, respectively. Notably, V008-1080 enhanced homology-directed repair (HDR) mediated by CRISPR/Cas9 while inhibiting non-homologous end joining (NHEJ) efficiency. Further investigations into the structure-activity relationships unveiled the binding sites and critical interactions between these small molecules and DNA-PKcs. This is the first application of DeepBindGCN_RG in a real drug screening task, and the successful discovery of a novel DNA-PKcs inhibitor demonstrates its efficiency as a core component in the screening pipeline. Moreover, this study provides important insights for exploring novel anticancer therapeutics and advancing the development of gene editing techniques by targeting DNA-PKcs.

Single-dose high-dose-rate brachytherapy versus two and three fractions for locally advanced prostate cancer.

BACKGROUND: Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS: 293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS: At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS: Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Dramatic Radiographic Response of Pelvis-Filling Locally Advanced Cervical Cancer Treated With Radiation and Chemotherapy.

Locally advanced cervical cancers are often treated with palliative intent due to concerns that the tumor is too far advanced or too large to be treated curatively. Also, patients greater than 65 years of age with cervical cancer are sometimes regarded as being too old or too frail to be cured with combined radiation and chemotherapy. These patients are often treated with radiation alone or with palliative therapy. Understanding the treatment modalities for cervical cancer is essential, as they can be complex and unique to each patient's specific diagnosis. This case report aims to describe the dramatic response to treatment with combined radiation and chemotherapy for a patient greater than 65 years of age with pelvis-filling cervical cancer with right-sided hydronephrosis. After a five-week course of concurrent chemoradiation, the cervical mass radiographically completely disappeared, with no evidence of disease noted on pelvic MRI.

HDR syndrome: Large cohort and systematic review.

HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3 variants, the penetrance of each associated condition is variable. Literature reviews have provided some answers, but many questions remain, in particular what the relationship is between genotype and phenotype. The current study examines 28 patients with HDR syndrome combined with an exhaustive review of the literature. Some conditions such as hearing loss are almost always present, while others described as rare initially, do not seem to be so rare after all (genital malformations and basal ganglia calcifications). By modeling pathogenic GATA3 variants found in HDR syndrome, we found that missense variations appear to always be located in the same area (close to the two Zinc Finger domain). We describe new pathogenic GATA3 variants, of which some seem to always be associated with certain conditions. Many audiograms were studied to establish a typical audiometric profile associated with a phenotype in HDR. As mentioned in the literature, hearing function should always be assessed as early as possible and follow up of patients with HDR syndrome should include monitoring of parathyroid function and vesicoureteral reflux in order to prevent complications.

Practical experience with initial quality assurance of a high dose rate brachytherapy grid-based Boltzmann solver algorithm.

PURPOSE: The purpose of this study was to validate the use of a model-based dose calculation algorithm (MBDCA), Acuros BV, for high dose rate brachytherapy treatment planning for a community-based hospital with a Bravos afterloader. Based on published AAPM recommendations, this work details a practical approach for community-based clinics to complete initial validation of Acuros BV, in order to add a MBDCA to a TG-43 based brachytherapy treatment planning program. METHODS: Source dimensions and materials used in Acuros BV and TG-43 source models were compared to the physical source. TG-186 testing was completed with standardized test cases externally calculated with Monte Carlo compared to locally calculated with Acuros BV. Point doses calculated using TG-43 were compared to those calculated with Acuros BV in water at various dose grid settings. Secondary dose check software was used to evaluate dose distributions resembling clinical patient plans, both in water and on CT datasets representative of patient anatomy. RESULTS: The major source of discrepancy of source models was the length of modeled steel cable. TG-186 testing showed that the largest differences between Monte Carlo and Acuros BV dose distributions were located along the source axis for cases calculated in water, as well as located in regions of high dose gradients and within the applicator for the case calculated with a generic shielded applicator. An audit of point doses calculated with both TG-43 and Acuros BV in water found that dose grid settings significantly affected agreement. Secondary dose check software indicated that Acuros BV functioned satisfactorily, and a 5% threshold was adopted for secondary dose checks on gynecologic plans. CONCLUSION: This validation process indicated that Acuros BV met expected standards and affirmed its suitability for integration into this clinical practice's brachytherapy treatment planning.

Dosimetric benefits and preclinical performance of steerable needles in HDR prostate brachytherapy.

Prostate cancer patients with an enlarged prostate and/or excessive pubic arch interference (PAI) are generally considered non-eligible for high-dose-rate (HDR) brachytherapy (BT). Steerable needles have been developed to make these patients eligible again. This study aims to validate the dosimetric impact and performance of steerable needles within the conventional clinical setting. HDR BT treatment plans were generated, needle implantations were performed in a prostate phantom, with prostate volume > 55 cm3 and excessive PAI of 10 mm, and pre- and post-implant dosimetry were compared considering the dosimetric constraints: prostate V100 > 95 % (13.50 Gy), urethra D0.1cm3 < 115 % (15.53 Gy) and rectum D1cm3 < 75 % (10.13 Gy). The inclusion of steerable needles resulted in a notable enhancement of the dose distribution and prostate V100 compared to treatment plans exclusively employing rigid needles to address PAI. Furthermore, the steerable needle plan demonstrated better agreement between pre- and post-implant dosimetry (prostate V100: 96.24 % vs. 93.74 %) compared to the rigid needle plans (79.13 % vs. 72.86 % and 87.70 % vs. 81.76 %), with no major changes in the clinical workflow and no changes in the clinical set-up. The steerable needle approach allows for more flexibility in needle positioning, ensuring a highly conformal dose distribution, and hence, HDR BT is a feasible treatment option again for prostate cancer patients with an enlarged prostate and/or excessive PAI.

CRISPR-Cas9 delivery strategies and applications: Review and update.

Nowadays, a significant part of the investigations carried out in the medical field belong to cancer treatment. Generally, conventional cancer treatments, including chemotherapy, radiotherapy, and surgery, which have been used for a long time, are not sufficient, especially in malignant cancers. Because genetic mutations cause cancers, researchers are trying to treat these diseases using genetic engineering tools. One of them is clustered regularly interspaced short palindromic repeats (CRISPR), a powerful tool in genetic engineering in the last decade. CRISPR, which forms the CRISPR-Cas structure with its endonuclease protein, Cas, is known as a part of the immune system (adaptive immunity) in bacteria and archaea. Among the types of Cas proteins, Cas9 endonuclease has been used in many scientific studies due to its high accuracy and efficiency. This review reviews the CRISPR system, focusing on the history, classification, delivery methods, applications, new generations, and challenges of CRISPR-Cas9 technology.

Fletcher suit or ring: A comparison of Fletcher suit and ring applicators for retroverted uteri.

Purpose: Approximately 20% of women worldwide have a retroverted uterus. A retroverted uterus is closer to the rectum and may cause toxicity during brachytherapy. Upon manipulation, a small percentage turn anteverted. Conventional brachytherapy applicators are designed for an anteverted uterus and can pose issues during insertion. Modified Fletcher suit and ring applicators have major differences in their geometry to achieve similar target coverage, and were analyzed in this study with respect to immediate adverse events and dosimetry. Material and methods: Three hundred seventy-four consecutive applications performed over a 20-month period were studied retrospectively to identify intra-cavitary applications (ICAs) in retroverted uteri. Cases were divided into 2 groups: modified Fletcher suit applicator with hemi-ovoids (group A) and ring applicator (group B). D2cc for bladder and rectum were noted, and acute adverse events were recorded. Results: Seventy-five applications were identified, out of which 47 cases used Fletcher suit applicator, and 28 cases used ring applicator. The median bladder D2cc for group A and B were 5.98 Gy and 6.3 Gy, respectively, and the median rectum D2cc was 5.27 Gy and 3.68 Gy, respectively; the median dose prescribed to point A was 6 Gy (range, 5.5-9.0 Gy). All patients had a point A coverage between 97% and 102%. Eighteen cases in both groups complained of pain requiring analgesics. Twenty-five cases (53.2%) and 20 cases (71.4%) in group A and B, respectively, required dose optimization, which was statistically insignificant (p > 0.11). A significant difference was identified (p < 0.00001) in rectal doses. A higher reported pain was noted in ring applicator group (p < 0.03). No patient experienced a profuse bleeding. Conclusions: In most parameters, the two applicators demonstrated comparable results. The control of rectal dosage is superior in the ring applicator at the cost of higher pain incidence. Patient's comfort and rectal dose in EBRT should be taken into consideration, with preference given to the ring applicator.

Acute toxicity outcomes from salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after prior radiotherapy.

Purpose: Isolated intra-prostatic recurrence of prostate adenocarcinoma after definitive radiotherapy presents a challenging clinical scenario. Salvage options require specialized expertise and pose risks of harm. This study aimed to present the acute toxicity results from using salvage high-dose-rate brachytherapy (sHDR-BT) as treatment in locally recurrent prostate cancer cases. Material and methods: Seventeen consecutive patients treated with sHDR-BT between 2019 and 2022 were evaluated retrospectively. Eligible patients had to have received curative intent prostate radiotherapy previously, and showed evidence of new biochemical failure. Evaluation with American Urological Association (AUA) and Common Terminology Criteria for Adverse Events (CTCAE) symptom assessments were performed for each case. Results: The median (inter-quartile range) age prior to salvage treatment was 68 (66-74) years. The median post-sHDR-BT follow-up time was 20 (13-24) months. At baseline prior to sHDR-BT, 8 (47%) patients had significant lower urinary tract symptoms. The median AUA score prior to sHDR-BT was 7 (3-18). Three (18%) patients reported irregular bowel function and 2 (12%) reported hematochezia prior to sHDR-BT. One-month post-treatment, the median AUA score was 13 (8-21, p = 0.21). Using CTCAE scoring, there were no cases of grade 2+ bowel or rectal toxicity, and no cases of grade 3+ urinary toxicity. Reported grade 2 urinary toxicities included 10 (59%) cases of bladder spasms, 2 (12%) cases of incontinence, 1 (6%) urinary obstruction, and 4 (24%) reports of urinary urgency. All these adverse events were temporary. Conclusions: This study adds to the existing literature by demonstrating that the acute toxicity profile of sHDR-BT is acceptable even without intra-operative magnetic resonance (MR) guidance or image registration. Further study is ongoing to determine long-term efficacy and toxicity of treatment.

Effect of Welding Current on Corrosion Resistance of Heat-Affected Zones of HDR Duplex Stainless Steel.

This paper examines the corrosion behavior of the welding heat-affected zone (HAZ) of HDR (high chromium, duplex, corrosion-resistant) duplex stainless steel, which currently faces corrosion-related challenges in marine seawater systems. The corrosion behavior of the HAZ was studied using microstructure analysis, polarization curve experiments, and double-loop potentiodynamic reactivation experiments. The results show that (1) the covering welding current can promote the formation of austenite in the HAZ, and that the covering welding current has no strict correspondence with the formation of austenite; (2) increasing the welding gap properly can facilitate the formation of austenite; (3) increasing the covering welding current enhances the material's pitting resistance, and a covering welding current of 70 A, coupled with a covering welding current of 100 A, represents a reasonable choice in terms of achieving a stronger pitting resistance; (4) in terms of intergranular corrosion resistance, increasing the covering welding current is not conducive to the intergranular corrosion resistance of the material, as the covering current will promote the precipitation of the secondary phase at the grain boundary, thus reducing its intergranular corrosion resistance; and (5) reducing the welding current appropriately contributes to improving the stability of the grain boundary.

A Case of High-Dose-Rate Brachytherapy Under Endoscopic Retrograde Cholangiopancreatography (ERCP) for Intraductal Papillary Neoplasm of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) represents a relatively nascent pathological entity, recognized as a precancerous condition within the spectrum of cholangiocarcinoma. Surgical intervention is advocated for all patients with IPNB due to their susceptibility toward obstructive jaundice, cholangitis, and the heightened likelihood of malignant transformation. Nonetheless, the efficacy of radiation therapy for IPNB cases that are either inoperable or refractory remains inadequately substantiated. Herein, we present a case study of an IPNB patient who declined surgery, and a commendable local control was accomplished solely through the implementation of brachytherapy utilizing Ir-192. A septuagenarian Japanese man presented at our medical institution with the chief complaint of jaundice and was subsequently diagnosed with IPNB. The IPNB lesion extensively spanned from the lower intrapancreatic bile duct to the right (extending to B5/B8) and left bile ducts (up to just before B4). The patient underwent weekly endoscopic retrograde cholangiopancreatography (ERCP) sessions. The prescribed treatment regimen encompassed 36 Gy/6 Fr high-dose-rate brachytherapy (HDR-BT) administered once per week during ERCP, with each treatment session adhering to a timeframe not exceeding two hours. Two months following the initiation of treatment, a biliary endoscopy demonstrated complete resolution of the tumor lesion and amelioration of jaundice. The only observed acute adverse event was grade 2 hepatic dysfunctions. To the best of our knowledge, this represents the first documented instance of HDR-BT employed in IPNB management, suggesting its potential as a viable alternative for inoperable or refractory IPNB cases.

Brachytherapy in gynecological malignancies at a tertiary care hospital: An analysis.

Purpose: Brachytherapy plays a crucial role in the standard of care for locally advanced gynecological malignancies. In this report, we present the experience from a tertiary teaching hospital, which is a referral center for image-guided brachytherapy (IGBT) in the management of locally advanced gynecological malignancies. Material and methods: This was a retrospective study of 130 patients referred to our hospital for IGBT after receiving initial external beam radiotherapy in their primary healthcare facilities, from January 2021 till January 2023. CT-based planning was done to delineate high-risk clinical target volume (HR-CTV). Dose of 6-7.5 Gy in 3-4 fractions was prescribed. Overall treatment time (OTT) was calculated, and patients were assessed for clinical response and toxicity after three months. Results: All patients received IGBT using an intra-cavitary or interstitial technique. The D90 HR-CTV mean EQD2 dose was 28.34 ±2.78 Gy. The mean EQD2 dose to 2 cc of the bladder, rectum, and sigmoid was 18.31 ±5.19 Gy, 14.14 ±5.76 Gy, and 17.43 ±4.75 Gy, respectively. The median interval time between the last fraction of external beam radiation therapy (EBRT) and first evaluation in the hospital was 19 (range, 13-28) days (interquartile range [IQR]). The median time between the completion of chemoradiation and brachytherapy procedure was 25 (range, 19-33) days (IQR). The mean overall treatment time (OTT) was 63.5 ±14.7 days. Conclusions: This study highlights the established advantages of image-guided interstitial brachytherapy and associated challenges. To optimize the overall treatment duration, it is imperative to prioritize and update the referral processes for brachytherapy centers.

Clinical implementation of failure modes and effects analysis for gynecological high-dose-rate brachytherapy.

Purpose: To use failure modes and effects analysis (FMEA) to identify failure modes for gynecological high-dose-rate (HDR) brachytherapy pathway and score with severity, occurrence, and detectability. Material and methods: A research team was organized to observe gynecological HDR brachytherapy pathway, and draw detailed process map to identify all potential failure modes (FMs). The whole team scored FMs based on three parameters, including occurrence (O), detectability (D), and severity (S), and then multiplied three scores to obtain risk priority number (RPN). All FMs were ranked according to RPNs and/or severity scores, and FMs with the highest RPN scores (> 100) and severity scores (> 8) were selected for in-depth analysis. Fault tree analysis (FTA) was applied to find progenitor causes of high-risk FMs and their propagation path, and determine which steps in the process need to be changed and optimized. Efficiency of each existing preventive methods to detect and stop FMs was analyzed, and proposals to improve quality management (QM) and ensure patient safety were suggested. Results: The whole gynecological HDR brachytherapy pathway consisted of 5 sub-processes and 30 specific steps, in which 57 FMs were identified. Twelve high-risk FMs were found, including 7 FMs with RPNs > 100 and 5 FMs with severity scores > 8. For these FMs, 2 were in the insertion stage, 1 in the imaging stage, 4 in the treatment planning stage, and 5 in the final stage of treatment delivery. The most serious of these FMs was the change in organ at risk (OAR) during treatment delivery (RPN = 245.7). The FM that occurred most frequently was the applicator shift during patient transfer. Conclusions: Failure modes and effects analysis is a prospective risk-based tool that can identity high-risk steps before failures occur, provide preventive measures to stop their occurrence, and improve quality management system.

Safety of high-dose-rate brachytherapy in patients with prostate cancer and inflammatory bowel disease: A case series.

Introduction: Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. Material and methods: We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. Results: Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. Conclusions: HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

Clinical outcomes of adaptive intracavitary and interstitial brachytherapy technique in locally advanced cervical cancer: A real-world data.

PURPOSE: To evaluate clinical outcomes of CT-based adaptive intracavitary and interstitial brachytherapy (IC followed by IC-ISBT) in locally advanced cervical cancer (LACC) in resource-constrained settings. METHODS AND MATERIALS: LACC patients treated with adaptive brachytherapy techniques were analyzed to evaluate treatment characteristics and clinical outcomes. The Kaplan-Meier method was used for survival analysis, and the log-rank test for univariate analysis. RESULTS: Out of 141 eligible patients with LACC, 87 (61.7%) patients received external beam radiotherapy (EBRT) in referral hospitals, while 54 (38.3%) were treated at our center. We divided our cohort into two groups: poor EBRT responder group (n = 70 [49.6%]) where IC-ISBT was adapted to achieve optimum tumor doses and OAR optimization group 71 (50.4%) where IC-ISBT was performed to reduce OAR doses. Median HRCTV-D90 dose was 88 Gy (range 70-109 Gy) with median HRCTV volume 33cc (range 15-96). Median D2cc doses to OARs were 90 Gy (range 70-107), 71 Gy (range 55-105) and 70 Gy (range 47-90) to bladder, rectum and sigmoid, respectively. At median follow-up of 32 months, 3-year local control (LC), locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) were 83%, 75%, 64% and 72%, respectively. Subgroup analysis revealed significantly better outcomes for OAR optimization compared to poor EBRT responders, with 3-year LC (95% vs. 70.1%, p < 0.001), LRC (87.3% vs. 62.7%, p < 0.001), DFS (79.2% vs. 49.4%, p < 0.001), and OS (86.2% vs. 57.4%, p < 0.001) CONCLUSION: In resource-constrained settings, implementation of Adaptive IC-ISBT is a viable alternative for optimizing OAR doses in LACC. However proactive approach employing IC-ISBT for tumor dose-escalation from first fraction of BT is warranted for improving LC in poor EBRT responders.

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.