Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

Novel intraocular shielding device for eye plaque brachytherapy using magnetite nanoparticles: A proof-of-concept study using radiochromic film and Monte Carlo simulations.

PURPOSE: Eye plaque brachytherapy is a mainstay treatment for uveal melanomas despite potential toxicities to normal tissues. This work proposes a nanoparticle ferrofluid as a novel intraocular shielding device. With a modified magnetic plaque, the shielding particles are drawn to the tumor surface, attenuating dose beyond the tumor while maintaining prescription dose to the target. METHODS AND MATERIALS: Ferromagnetic nanoparticles suspended in a silicone polymer were synthesized to provide a high-density shielding medium. The ferrofluid's half-value layer (HVL) was quantified for 125I photons using radiochromic film and Monte Carlo methods. A magnetic COMS plaque was created and evaluated in its ability to attract ferrofluid over the tumor. Two ferrofluid shielding mediums were evaluated in their ability to attenuate dose at adjacent structures with in vitro measurements using radiochromic film, in addition to Monte Carlo studies. RESULTS: The shielding medium's HVL measured approximately 1.3 mm for an 125I photon spectrum, using film and Monte Carlo methods. With 0.8 mL of shielding medium added to the vitreous humor, it proved to be effective at reducing dose to normal tissues of the eye. Monte Carlo-calculated dose reductions of 65%, 80%, and 78% at lateral distances 5, 10, and 18 mm from a tumor (5-mm apical height) in a modeled 20-mm COMS plaque. CONCLUSIONS: The magnitude of dose reduction could reduce the likelihood of normal tissue side effects for plaque brachytherapy patients, including patients with normal tissues close to the plaque or tumor. Additional studies, safety considerations, and preclinical work must supplement these findings before use.

Monte Carlo-based optimization of glioma capsule design for enhanced brachytherapy.

The use of radiotherapy in tumor treatment has become increasingly prominent and has emerged as one of the main tools for treating malignant tumors. Current radiation therapy for glioma employs 125I seeds for brachytherapy, which cannot be combined with radiotherapy and chemotherapy. To address this limitation, this paper proposes a dual-microcavity capsule structure that integrates radiotherapy and chemotherapy. The Monte Carlo simulation method is used to simulate the structure of the dual-microcavity capsule with a 125I liquid radioactive source. Based on the simulation results, two kinds of dual-microcavity capsule structures are optimized, and the optimized dual-microcavity capsule structure is obtained. Finally, the dosimetric parameters of the two optimized dual-microcavity capsule structures are analyzed and compared with those of other 125I seeds. The optimization tests show that the improved dual-capsule dual-microcavity structure is more effective than the single-capsule dual-microcavity structure. At an activity of 5 mCi, the average absorbed dose rate is 71.2 cGy/h in the center of the optimized dual-capsule dual-microcavity structure and 45.8 cGy/h in the center of the optimized single-capsule dual-microcavity structure. Although the radial dose function and anisotropy function exhibite variations from the data of other 125I seeds, they are generally similar. The absorbed dose rate decreases exponentially with increasing distance from the center of the capsule, which can reduce the damage to the surrounding tissues and organs while increasing the dose. The capsule structure has a better irradiation effect than conventional 125I seeds and can accomplish long-term, stable, low-dose continuous irradiation to form local high-dose radiation therapy for glioma.

Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma.

PURPOSE: Brachytherapy with episcleral plaques is the most common primary tumor treatment for uveal melanoma. This study aimed to compare the risk of tumor recurrence and metastatic death between 2 frequently used ruthenium 106 plaque designs: CCB (20.2 mm) and CCA (15.3 mm). METHODS AND MATERIALS: Data were obtained from 1387 consecutive patients treated at St. Erik Eye Hospital, Stockholm, Sweden between 1981 and 2022 (439 with CCA and 948 with CCB plaques). During the period, scleral transillumination was performed to delineate tumor margins before plaque insertion, but accurate plaque positioning was not verified after scleral attachment, and no minimum scleral dose was used. RESULTS: Patients treated with CCA plaques had smaller tumors than those treated with CCB plaques (mean diameter, 8.6 vs 10.5 mm; P < .001). There were no differences in patient sex, age, tumor distance to the optic disc, tumor apex dose, dose rate, or in rates of ciliary body involvement, eccentric plaque placement, or adjunct transpupillary thermotherapy (TTT). The average difference between plaque and tumor diameter was greater with the CCB plaque, and a smaller difference was an independent predictor of tumor recurrence. The 15-year incidence of tumor recurrence was 28% and 15% after treatment with CCA and CCB plaques, respectively (competing risk analysis, P < .001). Multivariate Cox regression analysis revealed a lower risk for tumor recurrence with CCB plaques (hazard ratio, 0.50). Similarly, patients treated with CCB plaques had a lower risk for uveal melanoma-related mortality (hazard ratio, 0.77). The risk for either outcome was not lower for patients treated with adjunct TTT. Uni- and multivariate time-dependent Cox regressions demonstrated that tumor recurrence was associated with uveal melanoma-related and all-cause mortality. CONCLUSIONS: Compared with 20-mm plaques, brachytherapy with 15-mm ruthenium plaques is associated with a higher risk for tumor recurrence and death. These adverse outcomes may be avoided by increasing safety margins and implementing effective methods to verify accurate plaque positioning.

Organ sparing treatment for penile cancer using a 3D-printed high-dose-rate brachytherapy applicator.

PURPOSE: We present a case study of the treatment of localized squamous cell carcinoma on the glans penis with a custom-fabricated high-dose-rate (HDR) brachytherapy applicator. METHODS AND MATERIALS: A cylindrically shaped applicator was fabricated with eight embedded channels suitable for standard plastic brachytherapy catheters. An additional custom silicone bolus/sleeve was designed to be used with the 3D-printed applicator to provide an additional offset from the source to skin to reduce the surface dose and for patient comfort. RESULTS: The patient (recurrent cT1a penile cancer) underwent CT simulation, and the brachytherapy plan was created with a nominal prescription dose of 40 Gy in 10 fractions given bidaily to the surface, and 35 Gy at 5 mm depth. Dose coverage to the clinical target volume was 94% (D90). Most fractions were treated with only 5-10 min of setup time. Follow up visits up to 1 year showed no evidence of disease with no significant changes in urinary and sexual function and limited cosmetic detriment to the patient. CONCLUSIONS: Patient-specific organ-sparing HDR plesiotherapy using 3D printing technology can provide reliable and reproducible patient setup and may be effective in achieving disease control for superficial penile cancer, although preserving patient quality of life.

Brachytherapy in the prevention of recurrence of conjunctival melanoma : Results of a case report in a University Hospital in Valladolid, Spain.

AIM: Describe the results of brachytherapy in the prevention of recurrences in conjunctival melanoma (CM) and describe a dosimetric protocol. METHODS: Retrospective and descriptive case report. Eleven consecutive patients with a confirmed histopathological diagnosis of CM treated with brachytherapy between 1992 and 2023 were reviewed. Demographic, clinical, and dosimetric characteristics as well as recurrences were recorded. Quantitative variables were represented by the mean, median, and standard deviation, and qualitative variables by frequency of distribution. RESULTS: Of a total of 27 patients diagnosed with CM, 11 who were treated with brachytherapy were included in the study (7 female; mean age at time of treatment: 59.4 years). Mean follow-up was 58.82 months (range 11-141 months). Of a total of 11 patients, 8 were treated with ruthenium-106 and 3 with iodine-125. Brachytherapy was performed in 6 patients as adjuvant therapy after biopsy-proven CM on histopathology and in the other 5 patients after recurrence. The mean dose was 85 Gy in all cases. Recurrences outside of the previously irradiated area were observed in 3 patients, metastases were diagnosed in 2 patients, and one case of an ocular adverse event was reported. CONCLUSION: Brachytherapy is an adjuvant treatment option in invasive conjunctival melanoma. In our case report, only one patient had an adverse effect. However, this topic requires further research. Furthermore, each case is unique and should be evaluated by experts in a multidisciplinary approach involving ophthalmologists, radiation oncologists, and physicists.

A novel multi-modality imaging phantom for validating interstitial needle guidance for high dose rate gynecological brachytherapy.

PURPOSE: To design, manufacture, and validate a female pelvic phantom for multi-modality imaging (CT, MRI, US) to benchmark a commercial needle tracking system with application in HDR gynecological (GYN) interstitial procedures. MATERIALS AND METHODS: A GYN needle-tracking phantom was designed using CAD software to model an average uterus from a previous patient study, a vaginal canal from speculum dimensions, and a rectum to accommodate a transrectal ultrasound (TRUS) probe. A target volume (CTVHR ) was designed as an extension from the cervix-uterus complex. Negative space molds were created from modeled anatomy and 3D printed. Silicone was used to cast the anatomy molds. A 3D printed box was constructed to house the manufactured anatomy for structural integrity and to accommodate the insertion of a speculum, tandem, needles, and TRUS probe. The phantom was CT-imaged to identify potential imperfections that might impact US visualization. Free-hand TRUS was used to guide interstitial needles into the phantom. The commercial tracking system was used to generate a 3D US volume. After insertion, the phantom was imaged with CT and MR and the uterus and CTVHR dimensions were verified against the CAD model. RESULTS/CONCLUSIONS: The manufactured phantom allows for accurate visualization with multiple imaging modalities and is conducive to applicator and needle insertion. The phantom dimensions from the CAD model were verified with those from each imaging modality. The phantom is low cost and can be reproducibly manufactured with the 3D printing and molding processes. Our initial experiments demonstrate the ability to integrate the phantom with a commercial tracking system for future needle tracking validation studies.

Deterioration of Visual Acuity after Brachytherapy and Proton Therapy of Uveal Melanoma, and Methods of Counteracting This Complication Based on Recent Publications.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The eyeball is the most common extracutaneous location of melanoma. UM is a huge threat to a patient's life. It metastasizes distantly via blood vessels, but it can also spread locally and infiltrate extraocular structures. The treatment uses surgical methods, which include, among others, enucleation and conservative methods, such as brachytherapy (BT), proton therapy (PT), stereotactic radiotherapy (SRT), stereotactic radiosurgery (SRS), transpupillary thermotherapy (TTT) and photodynamic therapy. The key advantage of radiotherapy, which is currently used in most patients, is the preservation of the eyeball with the risk of metastasis and mortality comparable to that of enucleation. Unfortunately, radiotherapy very often leads to a significant deterioration in visual acuity (VA) as a result of radiation complications. This article is a review of the latest research on ruthenium-106 (Ru-106) brachytherapy, iodine-125 (I-125) brachytherapy and proton therapy of uveal melanoma that took into account the deterioration of eye function after therapy, and also the latest studies presenting the new concepts of modifications to the applied treatments in order to reduce radiation complications and maintain better visual acuity in treated patients.

Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

OBJECTIVE: The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. PATIENTS AND METHODS: We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. RESULTS: We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. CONCLUSIONS: We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

Safety and efficacy of CT-guided radioactive iodine-125 seed implantation as a salvage treatment for recurrent head and neck cancer after two or more courses of radiotherapy.

BACKGROUND: In the past, patients with recurrent head and neck cancer (rHNC) who had previously received a high dose of radiation and were unable to undergo surgery were mainly treated with palliative chemotherapy due to the high incidence of side effects from re-irradiation. With the development of radiotherapy technology, re-irradiation of recurrent lesions by radioactive iodine-125 seed implantation (RISI) has been proposed as a feasible therapeutic approach. This study aimed to investigate the safety and efficacy of computed tomography (CT)-guided RISI in the treatment of rHNC after two or more courses of radiotherapy, and to analyze the prognostic factors. METHODS: Data of 33 patients with rHNC who received CT-guided RISI after two or more courses of radiotherapy were collected and statistically analyzed. The median cumulative dose of the previous radiotherapy was 110 Gy. Short-term efficacy was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1) criteria, while adverse events were evaluated by Common Terminology Criteria for Adverse Events (version 5.0) criteria. RESULTS: The median gross tumor volume (GTV) was 29.5 cc, and the postoperative median dose to 90% of target volume (D90) was 136.8 Gy. For adverse reactions, enhanced pain was found in 3 (9.1%) patients, followed by grade 1 to 2 acute skin reactions in 3 (9.1%) patients, grade 2 to 3 late skin reactions in 2 (6.1%) patients, grade 1 to 2 early mucosal reactions in 4 (12.1%) patients, and mandibular osteonecrosis in 1 (3.0%) patient. Regarding the treatment efficacy, the 1- and 2-year local control (LC) rates were 47.8% and 36.4% (median LC time, 10 months), and the 1- and 2-year overall survival (OS) rates were 41.3% and 32.2% (median OS time, 8 months). The absence of adverse events was associated with better LC. CONCLUSIONS: CT-guided RISI, as a salvage therapy, demonstrated acceptable safety and efficacy in the treatment of rHNC after two or more courses of radiotherapy. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Register database (Registration No. ChiCTR2200063261 ) in September 2, 2022.

Cesium-131 brachytherapy for the treatment of brain metastases: Current status and future perspectives.

Adjuvant radiotherapy is often necessary following surgical resection of brain metastases to improve local tumor control and survival. Brachytherapy using cesium-131 offers a novel method for loco-regional radiotherapy. We reviewed the current literature reporting the use of cesium-131 brachytherapy for the treatment of brain metastases. Published studies and ongoing trials were reviewed to identify treatment protocols and clinical outcomes of cesium-131 brachytherapy for brain metastases. Cesium-131 brachytherapy was further compared to current outcomes for iodine-125 brachytherapy and stereotactic radiosurgery. Intraoperative brachytherapy allows patients to receive two treatment modalities in one setting while minimizing tumor cell repopulation. After initial interest, the use of iodine-125 brachytherapy has declined due to unfavorable rates of radiation necrosis without survival improvement. Recent data on intracavitary cesium-131 brachytherapy in brain metastases have demonstrated improved locoregional tumor control with low risks of radiation necrosis, with associated improvements in patients compliance and satisfaction. Cesium-131 isotope has a short half-life, delivers 90% of its dose within a month, shortens the time to initiation of systemic therapy compared to iodine-125 or external radiotherapy, and has an excellent radiation safety profile. Further analyses have demonstrated superior cost-effectiveness and quality-of-life improvement ratios of cesium-131 brachytherapy than adjuvant stereotactic radiosurgery. Cesium-131 brachytherapy is a safe and effective post-surgical treatment option for brain metastases with associated clinical and cost-effectiveness benefits in appropriately selected patients.

A precise and simple isodose-volume-based verification method for HDR and LDR brachytherapy plans.

PURPOSE: The American Association of Physicists in Medicine (AAPM) code of practice for brachytherapy physics recommends performing an independent treatment time calculation. For this we implemented an easy to use isodose-based verification method for HDR (high-dose-rate) and LDR (low-dose-rate) brachytherapy plans. MATERIAL AND METHODS: Dose-volume-based methods have been developed for Ir-192-based high-dose-rate (HDR) and I-125 prostate low-dose-rate (LDR) brachytherapy. They allow checking the integral dwell time or activity when the volume of a suitable isodose is known. The verification method was validated for 55 clinical HDR and 243 clinical LDR plans. RESULTS: For HDR brachytherapy, the mean absolute difference between the estimated and calculated integral dwell time was 0.8% ± 1.0% (n = 30) with a single-source path and 2.7% ± 1.1% (n = 25) for multiple source paths. The corresponding value for LDR brachytherapy was 1.8% ± 2.0% (n = 243). In HDR brachytherapy, the verification method depends slightly on the plan class when considering one or more than one source paths. Good agreement between the estimated and calculated integral dwell times was obtained based on the 2 Gy isodose. Unlike HDR brachytherapy, the parameters used in the verification method for LDR brachytherapy plan verification strongly depend on the type of seed distribution. So, we recommend using an isodose at the prescribed dose for prostate HDR therapy. CONCLUSIONS: Isodose-based verification methods are precise, do not presuppose dedicated tools, and are simple to implement in clinical practice.

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients.

PURPOSE: We evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALS: The safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models. RESULTS: The median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years. CONCLUSIONS: After PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.

An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

A "scoping" review of prostate brachytherapy and immune responses.

PURPOSE: Whether prostate brachytherapy (BT) results in opportunistic biological changes that can improve clinical outcomes is not well studied. We sought to investigate the impact of prostate BT on the immune system. MATERIALS AND METHODS: A scoping review was performed using PubMed/Scopus for papers published between 2011-2021. Search terms were "brachytherapy" AND "immune" AND "prostate". A total of 81 records were identified and 6 were selected for further review. RESULTS: 2 low-dose-rate BT papers (n=68) evaluated changes in the peripheral blood following I-125 monotherapy. Both showed significant increases in peripheral CD3+ and CD4+ T cells post-BT. One also demonstrated significant increases in Treg subsets up to 150 days post-BT. 4 high-dose-rate (HDR) studies (n=37) were identified, and all were done in combination with EBRT. The largest study (n=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature when comparing a pre-BT biopsy to one prior to a second HDR fraction. CONCLUSION: Prostate BT can invoke an immune activating phenotype; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to promote synergy between BT and the immune system.

A Systematic Comparison of Dose Distributions Delivered in 125I Plaque Brachytherapy and Proton Radiation Therapy for Ocular Melanoma.

PURPOSE: To characterize dose distributions with 125I plaque brachytherapy compared with proton radiation therapy for ocular melanoma for relevant clinical scenarios, based on tumor base diameter (d), apical height (h), and location. METHODS AND MATERIALS: Plaque and proton treatment plans were created for 4 groups of cases: (1) REF: 39 instances of reference midsize circular-base tumor (d = 12 mm, h = 5 mm), in locations varying by retinal clock hours and distance to fovea, optic disc, and corneal limbus; (2) SUP: 25 superiorly located; (3) TEMP: 25 temporal; and (4) NAS: 25 nasally located tumors that were a fixed distance from the fovea but varying in d (6-18 mm) and h (3-11 mm). For both modalities, 111 unique scenarios were characterized in terms of the distance to points of interest, doses delivered to fovea, optic disc, optic nerve at 3 mm posterior to the disc (ON@3mm), lens, and retina. Comparative statistical evaluation was performed with the Mann-Whitney U test. RESULTS: Superior dose distributions favored plaque for sparing of (1) fovea in large (d + h ≥ 21 mm) NAS tumors; (2) ON@3mm in REF cases located ≤4 disc diameters from disc, and in NAS overall. Protons achieved superior dose sparing of (1) fovea and optic disc in REF, SUP, and TEMP; (2) ON@3mm in REF >4 disc diameters from disc, and in SUP and TEMP; and (3) the lens center overall and lens periphery in REF ≤6 mm from the corneal limbus, and in TEMP with h = 3 mm. Although protons could completely spare sections of the retina, plaque dose was more target conformal in the high-dose range (50% and 90% of prescription dose). CONCLUSIONS: Although comparison between plaque and proton therapy is not straightforward because of the disparity in dose rate, prescriptions, applicators, and delivery techniques, it is possible to identify distinctions between dose distributions, which could help inform decisions by providers and patients.

Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.

OBJECTIVE: To investigate vascular and morphologic optic disc changes after slotted plaque radiation therapy for choroidal melanoma involving the optic disc. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Thirty-nine patients with choroidal melanoma involving the optic nerve. METHODS: Each melanoma was treated with palladium-103 slotted plaque brachytherapy (incorporating and/or surrounding the optic nerve sheath) between 2005 and 2019. Imaging of the optic nerve before and after radiation allowed for documentation and evaluation of optic nerve pallor and cup-to-disc ratio (CDR) changes. Optical coherence tomography (OCT) CDR measurements and intraocular pressure (IOP) were recorded pretreatment and at follow-up. Of these patients, 22 also had OCT angiography (OCT-A) images with sufficient quality for evaluation of blood vessel density and length. Differences in cup-to-disc measurements were correlated with changes in OCT-A-measured vessel density and length. RESULTS: Following slotted plaque radiation therapy, there was no significant increase in IOP or optic nerve pallor. OCT and colour photography revealed significant increases (both p < 0.001) in CDR from pretreatment to the last follow-up. Increased CDRs on OCT were significantly correlated to OCT-A-measured change in vessel length (p = 0.027). Similarly, increased CDR ratios on fundus photography were significantly correlated with OCT-A-measured change in vessel density (p = 0.043) and length (p = 0.019). CONCLUSION: Fundus photography and OCT measurements revealed increased optic disc cupping following slotted plaque radiation therapy. Cupping was associated with OCT-A evidence of synchronous progressive peripapillary vascular occlusion and attenuation. Therefore, slotted plaque radiation-induced peripapillary and papillary ischemia was associated with increased CDR ratios and optic disc cupping.

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis.

PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38). CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

Retinal and optic nerve relapse in retinoblastoma secondary to epiretinal and epipapillary vitreous seeds implantation documented by optical coherence tomography.

BACKGROUND: Retinal retinoblastoma growth phenotypes can be endophytic, exophytic, diffuse infiltrating or anterior diffuse. Herein, we describe a novel tumor growth pattern in two patients. MATERIAL AND METHODS: Imaging with spectral-domain optical coherence tomography (SD-OCT). RESULTS: Both cases were diagnosed with unilateral group D retinoblastoma treated with first-line or bridge intra-arterial chemotherapy (IAC). Case 1 had a new intravitreal/epiretinal relapse 3 months after brachytherapy and intravitreal chemotherapy. SD-OCT showed a disruption of the inner limiting membrane (INL) underneath a parapapillary epiretinal seed. The intravitreal/epiretinal disease completely regressed with intravitreal melphalan. Three months later, an isolated intraretinal growth was documented on SD-OCT at the site of previously INL disruption, which was treated by thermotherapy. He remained disease-free at 1-year follow-up with 0.6 visual acuity. Case 2 was seen 2 months after treatment interruption due to the COVID-19 pandemic. Fundus examination showed a massive intravitreal/epipapillary invasion completely obscuring the papilla. Salvage treatment of this seeing eye consisted of combined intra-arterial and intravitreal melphalan and topotecan injections. An infraclinical papillary regrowth 4 months later was treated with additional IAC. Six months later, enucleation was performed due to an infraclinical papillary relapse with suspicion of intralaminar invasion. Histopathology showed retrolaminar optic nerve invasion with tumor-free surgical section. The child received four cycles of adjuvant chemotherapy and remained disease-free at 1-year follow-up. CONCLUSION: Epiretinal/epipapillary vitreous seeding can be the source of a secondary intraretinal/optic nerve head relapse. SD-OCT is instrumental to follow such cases. Enucleation remains the safest option if secondary optic nerve invasion is suspected.

Is iodine-125 seed strand brachytherapy suitable for ureteral carcinoma?

BACKGROUND: Long-term conventional high-dose radiation therapy can lead to retroperitoneal fibrosis and nerve damage in patients with advanced ureteral carcinoma (UC). The purpose of this study is to evaluate the safety and efficacy of nephrostomy combined with iodine-125 seed strand (ISS) brachytherapy for the treatment of UC. MATERIALS AND METHODS: Twenty-one patients with UC were treated with nephrostomy combined with ISS brachytherapy. The following parameters were recorded: technical success rate, procedure time, complications, mean D90 (dose delivered to the 90% gross tumor volume), organ at risk (OAR) dose, local control rate (LCR), ureteral patency (UP), local tumor progression (LTP), and overall survival (OS). The hydronephrosis score (HS), visual analog score (VAS), Karnofsky score and maximum diameter (MD) were compared before and 8 weeks after the operation. RESULTS: The technical success rate was 100%, with a mean procedure time of 54.6 min. Three cases (14.5%) had bladder implant metastasis but no other major complications, such as ureteral perforation, infection, or severe bleeding, occurred. The mean D90 and OAR doses were 50.7 and 3.8 Gy, respectively. LCR was 100% with 28.6% UP at the 8-week evaluation. During the mean follow-up of 16.6 months, LTP occurred in 4 cases (19.1%), and the median OS was 25.0 months (95% CI 21.3-28.5). The HS, VAS, Karnofsky score and MD showed significant changes (all P < 0.01). CONCLUSION: UC can be safely and effectively treated by nephrostomy combined with ISS brachytherapy, a viable option for patients who cannot undergo or refuse surgical resection.