[Application of new imaging modalities for brachytherapy of cancer patients]. / Új képalkotó eljárások alkalmazása daganatos betegek brahiterápiájában.

In the Radiotherapy Centre of the National Institute of Oncology, Budapest, a 0.55 T MR scanner (MAGNETOM Free. Max) and a ring-like X-ray machine (ImagingRing) have been in operation since 2022. The MR scanner has a tunnel diameter of 80 cm, the X-ray machine has a ring diameter of 121 cm. The latter can also be used for cone-beam CT (CBCT) imaging. The MR scanner is mainly used for planning gynaecological brachytherapy (BT) treatments. Image distortions in MR imaging were investigated with a special grid phantom. After head and neck and breast implant, image quality of ImagingRing CBCT and planning CT was compared. The position of the radiation source was verified by radiographs taken during treatment. Despite the lower field strength, the image quality of the MR scanner was found to be adequate for treatment planning of gynaecological BT. Image distortions were found to be clinically negligible. On CBCT images obtained with ImagingRing, catheters could always be well identified, and anatomical organs were adequately visualized for head and neck treatments, but not for breast implants. The MR scanner is suitable for treatment planning for gynaecological BT due to its good image quality and low image distortion. The image quality of the ImagingRing is suitable for treatment planning for small body sizes, but not for larger sizes. The device can be used to in vivo check of the radiation source position during treatment.

Clinical and toxicity outcomes with 3D based-HDR surface mold brachytherapy in skin cancer.

INTRODUCTION: Surface mold brachytherapy (SMBT) is an established treatment modality in skin cancer, especially in accessible areas, and has shown comparable outcomes to surgery. We have presented our results for the skin tumor treatment with SMBT treated with high-dose-rate (HDR) brachytherapy in terms of clinical outcomes and toxicity at our institute. MATERIALS AND METHODS: In this retrospective analysis, 15 patients with skin cancer were treated with customized tube-based SMBT at our institute between January 2019 and July 2021. The patients were treated using HDR-brachytherapy using Iridium-192. The median dose was 40 Gy in 10 fractions. The dosimetric parameters were assessed, and patients were followed up as per the institutional protocol. All patients underwent individualized CT-based planning. Skin toxicity was assessed using the Dermatology Life Quality Index (DLQI). RESULTS: With the majority of the patients being male, the median age was 59 years and the most common site affected was the face (8/15; 53.3%). Among the 15 cases, five were squamous cell carcinoma, nine were basal cell carcinoma, and a single case of sebaceous cell carcinoma. The median depth of invasion was 4 mm, and the median catheter-to-surface distance was 1 mm. The complete response rate among the 10 definitive cases was 90% and partial response in one case. The treatment was well-tolerated with no grade 3-5 toxicities. The median V95% and V90% were 94.8% and 97.1%, respectively. The mean coverage index (C.I.), dose non-uniformity ratio (DNR), and overdose volume index (ODI) were 0.97, 0.13, and 0.05, respectively. After a median follow-up of 12 months, none of the patients had recurrence. On assessment of DLQI, the scores were found to be significant in association with the tumor size and tumor site with scores favoring <2 cm and non-exposed area lesions. CONCLUSION: SMBT is a safe and effective treatment modality for skin tumors providing excellent response and cosmetic outcomes. It is well-tolerated and a non-invasive option for elderly patients with comorbidities and lesions in inoperable areas.

Synergistic Effects of 125I Seed Implantation Brachytherapy and Gemcitabine in Pancreatic Tumors.

BACKGROUND: Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of 125I brachytherapy and gemcitabine (GEM) chemotherapy has a synergistic effect on pancreatic cancer (PC). METHODS: In vitro, PANC-1 cells in the exponential phase were treated with 125I radioactive seeds (6 Gy) and GEM (30 nM). Cell proliferation, apoptosis, and mitochondrial membrane potential were measured using the Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and flow cytometry, respectively. In vivo, we examined the inhibitory effect of three different treatment regimens on tumor growth in mice when combined with 125I brachytherapy and GEM. Next, we investigated the effects of the optimal scheme among the three on the tumor microenvironment, tumor tissue morphology, tumor cell apoptosis, systemic inflammatory response, and levels of apoptosis-related proteins in the tumor. Changes in the tumor microenvironment and levels of apoptosis-related proteins were measured by Western blot. The extent of damage to tumor tissue morphology was assessed by Hematoxylin and Eosin (HE) staining. Tumor cell apoptosis was measured by TUNEL staining. Changes in inflammation-related factors were determined by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results of in vitro cell experiments demonstrated that the combination of 125I radioactive seeds (6 Gy) and GEM (30 nM) had a stronger inhibitory effect on PANC-1 cells than either alone (p < 0.05). In vivo, data showed that the GEM (after 3 d) + 125I treatment group had the strongest tumor inhibition effect on PC (p < 0.05). Western blot analysis showed that the combined treatment of 125I brachytherapy and GEM caused changes in the expression of collagen and connexin in the tumor microenvironment, promoted tumor cell apoptosis, upregulated the expression of pro-apoptotic proteins, and helped to restore pancreatic function (p < 0.01). CONCLUSION: Our research results suggest that the strategy of 125I seed implantation surgery in mice after 3 days of GEM treatment has a more pronounced synergistic effect on the treatment of PC.

Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities.

BACKGROUND: The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. METHODS: The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan-Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. RESULTS: During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1-2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1-2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. CONCLUSIONS: 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Prostate Brachytherapy: Advancing Prostate Cancer Treatment in the Region.

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Treatment of Locally Recurrent Rectal Cancer: A Review.

ABSTRACT: Up to 10% of patients with locally advanced rectal cancer will experience locoregional recurrence. In the setting of prior surgery and often radiation and chemotherapy, these represent uniquely challenging cases. When feasible, surgical resection offers the best chance for oncologic control yet risks significant morbidity. Studies have consistently indicated that a negative surgical resection margin is the strongest predictor of oncologic outcomes. Chemoradiation is often recommended to increase the chance of an R0 resection, and in cases of close/positive margins, intraoperative radiation/brachytherapy can be utilized. In patients who are not surgical candidates, radiation can provide symptomatic relief. Ongoing phase III trials are aiming to address questions regarding the role of reirradiation and induction multiagent chemotherapy regimens in this population.

Investigations on the beam quality correction factor for ionization chambers in high-energy brachytherapy dosimetry.

Objective. To enhance the investigations on MC calculated beam quality correction factors of thimble ionization chambers from high-energy brachytherapy sources and to develop reliable reference conditions in source and detector setups in water.Approach. The response of five different ionization chambers from PTW-Freiburg and Standard Imaging was investigated for irradiation by a high dose rate Ir-192 Flexisource in water. For a setup in a Beamscan water phantom, Monte Carlo simulations were performed to calculate correction factors for the chamber readings. After exact positioning of source and detector the absorbed dose rate at the TG-43 reference point at one centimeter nominal distance from the source was measured using these factors and compared to the specification of the calibration certificate. The Monte Carlo calculations were performed using the restricted cema formalism to gain further insight into the chamber response. Calculations were performed for the sensitive volume of the chambers, determined by the methods currently used in investigations of dosimetry in magnetic fields.Main results. Measured dose rates and values from the calibration certificate agreed within the combined uncertainty (k= 2) for all chambers except for one case in which the full air cavity was simulated. The chambers showed a distinct directional dependence. With the restricted cema formalism calculations it was possible to examine volume averaging and energy dependence of the perturbation factors contributing to the beam quality correction factor also differential in energy.Significance. This work determined beam quality correction factors to measure the absorbed dose rate from a brachytherapy source in terms of absorbed dose to water for a variety of ionization chambers. For the accurate dosimetry of brachytherapy sources with ionization chambers it is advisable to use correction factors based on the sensitive volume of the chambers and to take account for the directional dependence of chamber response.

[Does radiation therapy for prostate cancer increase the risk of second cancers?] / La radiothérapie du cancer de la prostate augmente-t-elle le risque de seconds cancers ?

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

Iodine Plaque Brachytherapy a Customized Conservative Approach to the Management of Medium/Large-sized Uveal Melanoma.

BACKGROUND/AIM: The objective of this study was to assess the role of iodine (125I) plaque brachytherapy in the management of uveal melanoma. PATIENTS AND METHODS: This is a retrospective study of 50 patients (median age 67 years; range=33-86 years) with uveal melanoma, treated with 125I plaque brachytherapy at the University Hospital of Pisa. Uveal melanoma was diagnosed with A-scan and B-scan standardized echography, fluorescein angiography, indocyanine green-angiography, optical coherence tomography, and/or magnetic resonance imaging. The primary outcomes assessed were local control, overall survival, disease progression, globe preservation, and metastases. Secondary outcomes were acute and late radiation adverse effects. RESULTS: Inclusion criteria comprised Eastern Cooperative Oncology Group performance status ≤2, life expectancy >6 months, and tumor thickness ≤10 mm and\or diameter ≤20 mm. All the patients were treated with 125I plaque brachytherapy, with a prescription dose of 85 Gy to the tumor apex. The 5-year rate of local control, progression-free survival, metastasis-free survival, enucleation-free survival, and overall survival were 83.0%, 81.4%, 90.3%, 83.1%, and 92.1% respectively. Twenty-four patients (48.0%) had one or more acute and late toxicities. The most common acute adverse events (CTCAE vs. 5.0) grade 1-3 were conjunctivitis and eye pain (6.0%). Regarding late events, radiation retinopathy grade 1-3 occurred in 18.0% of cases, while grade 1-3 vitreous hemorrhage in 2.5%. CONCLUSION: 125I plaque brachytherapy offers an effective and safe approach for selected cases of uveal melanoma, due to the reported satisfactory results in terms of local control, eye conservation and survival.

125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy.

OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.

Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study.

BACKGROUND: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS: One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.

Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer.

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.

A prostate seed implantation robot system based on human-computer interactions: Augmented reality and voice control.

The technology of robot-assisted prostate seed implantation has developed rapidly. However, during the process, there are some problems to be solved, such as non-intuitive visualization effects and complicated robot control. To improve the intelligence and visualization of the operation process, a voice control technology of prostate seed implantation robot in augmented reality environment was proposed. Initially, the MRI image of the prostate was denoised and segmented. The three-dimensional model of prostate and its surrounding tissues was reconstructed by surface rendering technology. Combined with holographic application program, the augmented reality system of prostate seed implantation was built. An improved singular value decomposition three-dimensional registration algorithm based on iterative closest point was proposed, and the results of three-dimensional registration experiments verified that the algorithm could effectively improve the three-dimensional registration accuracy. A fusion algorithm based on spectral subtraction and BP neural network was proposed. The experimental results showed that the average delay of the fusion algorithm was 1.314 s, and the overall response time of the integrated system was 1.5 s. The fusion algorithm could effectively improve the reliability of the voice control system, and the integrated system could meet the responsiveness requirements of prostate seed implantation.

The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience.

BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.

Time-resolved clinical dose volume metrics, calculations and predictions based on source tracking measurements and uncertainties to aid treatment verification and error detection for HDR brachytherapy-a proof-of-principle study.

Objective.High-dose-rate (HDR) brachytherapy lacks routinely available treatment verification methods. Real-time tracking of the radiation source during HDR brachytherapy can enhance treatment verification capabilities. Recent developments in source tracking allow for measurement of dwell times and source positions with high accuracy. However, more clinically relevant information, such as dose discrepancies, is still needed. To address this, a real-time dose calculation implementation was developed to provide more relevant information from source tracking data. A proof-of-principle of the developed tool was shown using source tracking data obtained from a 3D-printed anthropomorphic phantom.Approach.Software was developed to calculate dose-volume-histograms (DVH) and clinical dose metrics from experimental HDR prostate treatment source tracking data, measured in a realistic pelvic phantom. Uncertainty estimation was performed using repeat measurements to assess the inherent dose measuring uncertainty of thein vivodosimetry (IVD) system. Using a novel approach, the measurement uncertainty can be incorporated in the dose calculation, and used for evaluation of cumulative dose and clinical dose-volume metrics after every dwell position, enabling real-time treatment verification.Main results.The dose calculated from source tracking measurements aligned with the generated uncertainty bands, validating the approach. Simulated shifts of 3 mm in 5/17 needles in a single plan caused DVH deviations beyond the uncertainty bands, indicating errors occurred during treatment. Clinical dose-volume metrics could be monitored in a time-resolved approach, enabling early detection of treatment plan deviations and prediction of their impact on the final dose that will be delivered in real-time.Significance.Integrating dose calculation with source tracking enhances the clinical relevance of IVD methods. Phantom measurements show that the developed tool aids in tracking treatment progress, detecting errors in real-time and post-treatment evaluation. In addition, it could be used to define patient-specific action limits and error thresholds, while taking the uncertainty of the measurement system into consideration.

Multimodality management of locoregionally extensive Marjolin ulcer: a case report and review of the literature.

BACKGROUND: Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar. CASE REPORT: A 20-year-old male who sustained a flame burn over the scalp at 3 months of age developed a nonhealing ulcer over the burn scar 20 years later, which was treated with adequate surgical margins with adjuvant mold brachytherapy. Two months after completion of that treatment, he developed parotid nodal metastasis with positron emission tomography (PET)-positive bilateral cervical, supraclavicular, right suboccipital, and mesenteric lymph nodes that were treated with concurrent chemoradiation. One month later, the patient developed an ulcerative lesion involving the left parotid region with PET showing infiltration of the parotid gland, but with resolution of other previous sites of uptake. The patient was treated surgically with radical parotidectomy with elective neck dissection and reconstruction with locoregional flap. At 6-month follow-up, the patient developed extensive locoregional recurrence and distant metastasis and was started on oral metronomic therapy. The patient was alive with stable disease at 3-month follow-up after initiation of palliative chemotherapy. CONCLUSION: Despite timely multimodality therapy, MU may present with a hostile clinical course with a short disease-free interval and early recurrence.

Comparative Single Vesicle Analysis of Aqueous Humor Extracellular Vesicles before and after Radiation in Uveal Melanoma Eyes.

Small extracellular vesicles (sEVs) have been shown to promote tumorigenesis, treatment resistance, and metastasis in multiple cancer types; however, sEVs in the aqueous humor (AH) of uveal melanoma (UM) patients have never previously been profiled. In this study, we used single particle analysis to characterize sEV subpopulations in the AH of UM patients by quantifying their size, concentration, and phenotypes based on cell surface markers, specifically the tetraspanin co-expression patterns of CD9, CD63, and CD81. sEVs were analyzed from paired pre- and post-treatment (brachytherapy, a form of radiation) AH samples collected from 19 UM patients. In post-brachytherapy samples, two subpopulations, CD63/81+ and CD9/63/81+ sEVs, were significantly increased. These trends existed even when stratified by tumor location and GEP class 1 and class 2 (albeit not significant for GEP class 2). In this initial report of single vesicle profiling of sEVs in the AH of UM patients, we demonstrated that sEVs can be detected in the AH. We further identified two subpopulations that were increased post-brachytherapy, which may suggest radiation-induced release of these particles, potentially from tumor cells. Further study of the cargo carried by these sEV subpopulations may uncover important biomarkers and insights into tumorigenesis for UM.

Inter-observer effects in needle reconstruction for temporary prostate brachytherapy: Dosimetric implications and adaptive CBCT-TRUS registration solutions.

PURPOSE: To investigate geometric and dosimetric inter-observer variability in needle reconstruction for temporary prostate brachytherapy. To assess the potential of registrations between transrectal ultrasound (TRUS) and cone-beam computed tomography (CBCT) to support implant reconstructions. METHODS AND MATERIALS: The needles implanted in 28 patients were reconstructed on TRUS by three physicists. Corresponding geometric deviations and associated dosimetric variations to prostate and organs at risk (urethra, bladder, rectum) were analyzed. To account for the found inter-observer variability, various approaches (template-based, probe-based, marker-based) for registrations of CBCT to TRUS were investigated regarding the respective needle transfer accuracy in a phantom study. Three patient cases were examined to assess registration accuracy in-vivo. RESULTS: Geometric inter-observer deviations >1 mm and >3 mm were found for 34.9% and 3.5% of all needles, respectively. Prostate dose coverage (changes up to 7.2%) and urethra dose (partly exceeding given dose constraints) were most affected by associated dosimetric changes. Marker-based and probe-based registrations resulted in the phantom study in high mean needle transfer accuracies of 0.73 mm and 0.12 mm, respectively. In the patient cases, the marker-based approach was the superior technique for CBCT-TRUS fusions. CONCLUSION: Inter-observer variability in needle reconstruction can substantially affect dosimetry for individual patients. Especially marker-based CBCT-TRUS registrations can help to ensure accurate reconstructions for improved treatment planning.

Reproducibility and air gap pockets of 3D-printed brachytherapy applicator placement in high-dose-rate skin cancer.

BACKGROUND AND PURPOSE: This study aimed to investigate the reproducibility of a novel approach using 3D printed brachytherapy applicators for the treatment of skin cancer. Specifically, we aimed to assess the accuracy of applicator placement and to minimize the existence of air gap pockets between the applicator and the patient's skin. MATERIALS AND METHODS: A total of 20 patients plans diagnosed with skin cancer were enrolled in this study. All patients underwent high dose rate (HDR) brachytherapy. To ensure precise applicator placement, patient-specific 3D printed applicators were designed based on individual body and tumor topography, utilizing data obtained from computer tomography (CT) scans. All applicators were fabricated using fused deposition modeling technology. RESULTS: The error in applicator placement was measured and found to be less than 1.0 mm on average, with a standard deviation of 0.9 mm. Additionally, the average error in air gap pockets between the applicator and the patient's skin was 0.4 mm (standard deviation was 0.5 mm). The study demonstrated that the personalized approach of 3D printed brachytherapy applicator placement in skin cancer treatment yielded highly accurate results. The average error of less than 1.0 mm in applicator positioning and the minimal air gap pockets demonstrated the reproducibility and precision of this technique. CONCLUSION: Our study establishes the reproducibility and accuracy of 3D-printed brachytherapy applicator placement in the treatment of skin cancer. This personalized treatment approach offers a highly precise method for delivering radiation therapy, minimizing the risk to adjacent healthy tissues, and enhancing overall patient outcomes.

External Beam Radiotherapy in the Management of Uveal Melanoma.

OPINION STATEMENT: Uveal melanoma is the most common primary ocular tumor in adults. With the evidence demonstrating that episcleral plaque brachytherapy (EPB) has similar survival rates as enucleation in the Collaborative Ocular Melanoma Study (COMS), eye-sparing treatments have come to the fore today. External radiotherapy techniques (proton beam radiotherapy and stereotactic radiosurgery/fractionated stereotactic radiosurgery) are an important treatment option for globe-sparing treatments. There are no prospective randomized trials comparing these techniques; however, retrospective series, meta-analyses, and reviews indicate that these EPB and external radiotherapy techniques are equal. With this review, we aimed to examine the external radiotherapy techniques used in the treatment of uveal melanoma in detail with reference to the current literature.