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1.
Sci Rep ; 14(1): 14866, 2024 06 27.
Article in English | MEDLINE | ID: mdl-38937505

ABSTRACT

Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 1013 Gy/s in very short pulses (10-13 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.


Subject(s)
Coculture Techniques , Electrons , Lasers , Humans , Coculture Techniques/methods , Cell Line, Tumor , Melanocytes/radiation effects , DNA Damage , Melanoma/radiotherapy , Melanoma/pathology , DNA Breaks, Double-Stranded/radiation effects
2.
Int J Mol Sci ; 25(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892225

ABSTRACT

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.


Subject(s)
Aqueous Humor , Brachytherapy , Extracellular Vesicles , Melanoma , Uveal Neoplasms , Humans , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/metabolism , Uveal Neoplasms/pathology , Extracellular Vesicles/metabolism , Melanoma/radiotherapy , Melanoma/metabolism , Melanoma/pathology , Aqueous Humor/metabolism , Aqueous Humor/radiation effects , Female , Male , Middle Aged , Aged , Biomarkers, Tumor/metabolism , Adult , Aged, 80 and over
3.
Curr Treat Options Oncol ; 25(7): 932-951, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38869695

ABSTRACT

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.


Subject(s)
Brachytherapy , Disease Management , Melanoma , Radiosurgery , Uveal Neoplasms , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/mortality , Humans , Melanoma/radiotherapy , Melanoma/mortality , Brachytherapy/methods , Radiosurgery/methods , Treatment Outcome , Proton Therapy/methods
4.
In Vivo ; 38(4): 1814-1822, 2024.
Article in English | MEDLINE | ID: mdl-38936895

ABSTRACT

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.


Subject(s)
Brachytherapy , Iodine Radioisotopes , Melanoma , Uveal Neoplasms , Humans , Melanoma/radiotherapy , Melanoma/mortality , Melanoma/pathology , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/mortality , Uveal Neoplasms/pathology , Female , Male , Brachytherapy/methods , Brachytherapy/adverse effects , Middle Aged , Aged , Adult , Iodine Radioisotopes/therapeutic use , Aged, 80 and over , Treatment Outcome , Retrospective Studies , Disease Management
6.
Cesk Slov Oftalmol ; 80(3): 170-174, 2024.
Article in English | MEDLINE | ID: mdl-38886109

ABSTRACT

The aim of the thesis is to present the case of a patient in whom bilateral calcification of the hydrophilic intraocular lens (IOL) Lentis M+ LS-313 MF30 (Oculentis) has developed. Due to the negative effect on visual functions, explantation and replacement of the artificial lens was necessary in both eyes. Case Report: An overview of the available literature summarized the diagnostics, current examination methods and possibilities of the surgical solution of calcification of the bifocal hydrophilic lens Lentis M+ LS-313 MF30 (Oculentis). The specific solution is described in a case report of a patient in whom calcification of both lenses developed 6 years after implantation of the IOL. In 2015, the patient underwent uncomplicated cataract surgery of both eyes with the implantation of an artificial intraocular lens into the capsule. In September 2021, an 82-year-old man was examined at our outpatient clinic for deterioration of visual acuity and changes in the material of the artificial IOL which were perceptible during a clinical examination, on the recommendation of a local ophthalmologist. Blurred vision predominated. A diagnosis of intraocular lens opacification was confirmed and documented using a Scheimpflug camera (OCULUS Pentacam HR) and anterior OCT (Avanti RTVue XR Optovue,). The patient was indicated for explantation and replacement of the opacified intraocular lens in the left and subsequently in the right eye- The same type of IOL was used for reimplantation with good functional results. Conclusion: Since 2010, multifocal lens implantation has been on an upward trend worldwide. This type of MF IOL has also been used in thousands of implantations. A number of other explantations can be expected in the coming years. The optimal solution is the correct replacement of the calcified IOL with the same construction made of safer hydrophobic material.


Subject(s)
Melanoma , Radiosurgery , Humans , Male , Radiosurgery/adverse effects , Melanoma/radiotherapy , Aged, 80 and over , Calcinosis/surgery , Calcinosis/diagnostic imaging , Choroid Neoplasms/radiotherapy , Choroid Neoplasms/diagnosis , Lenses, Intraocular/adverse effects , Radiation Injuries/etiology , Radiation Injuries/diagnosis , Radiation Injuries/surgery , Uveal Neoplasms/radiotherapy , Lens Implantation, Intraocular/adverse effects
7.
Invest Ophthalmol Vis Sci ; 65(6): 7, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38833258

ABSTRACT

Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.


Subject(s)
Chromosomes, Human, Pair 3 , DNA Damage , Melanoma , Uveal Neoplasms , Humans , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/genetics , Melanoma/radiotherapy , Melanoma/genetics , Female , Chromosomes, Human, Pair 3/genetics , Male , Middle Aged , Aged , Adult , Aged, 80 and over , In Situ Hybridization, Fluorescence , In Situ Nick-End Labeling , Radiotherapy Dosage , Immunohistochemistry , Radiosurgery/adverse effects , Radiosurgery/methods , Dose-Response Relationship, Radiation
8.
Arch Dermatol Res ; 316(6): 244, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795247

ABSTRACT

Melanoma, accounting for a significant proportion of skin cancer-related deaths, has variable survival outcomes based on the stage at diagnosis and treatment efficacy. Traditional treatments, while effective, pose risks of scarring and systemic side effects. Laser therapy offers an emerging non-surgical alternative, with CO2 lasers particularly showing promise in palliative care.A comprehensive search was conducted using PubMed, focusing on laser therapy for melanoma treatment. The search included studies on both stand-alone and adjunct laser therapies, with inclusion criteria requiring peer-reviewed articles detailing treatment outcomes for primary, recurrent, or metastatic melanoma.The literature shows that laser therapy for melanoma falls into four major types when categorized by laser medium: solid-state, diode, pulse-dye, and gas (CO2). Data on solid-state lasers for melanoma are limited and their use remains controversial. However, one study with high-energy pulsed neodymium lasers reported a 5-year survival of 82.9% with minimal adverse effects for primary melanoma. CO2 laser therapy has been effective for palliative treatment, with one study showing 54.8% of patients with recurrent melanoma surviving 5.4 years post-ablation. For metastatic melanoma, numerous studies have shown that CO2 laser therapy can provide symptomatic relief and disease control. Combination therapies using lasers and immune-based therapies have demonstrated enhanced outcomes and immune activation, highlighting the potential of laser therapies in melanoma management.While traditional treatments remain the standard for primary melanoma, laser therapies, particularly CO2 laser ablation, show substantial promise in palliative care for metastatic melanoma. Careful patient selection and assessment are crucial for achieving positive outcomes.


Subject(s)
Melanoma , Palliative Care , Skin Neoplasms , Humans , Melanoma/therapy , Melanoma/mortality , Melanoma/surgery , Melanoma/radiotherapy , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Palliative Care/methods , Treatment Outcome , Lasers, Gas/therapeutic use , Lasers, Gas/adverse effects , Laser Therapy/methods , Laser Therapy/adverse effects , Combined Modality Therapy , Lasers, Solid-State/therapeutic use , Lasers, Solid-State/adverse effects , Neoplasm Recurrence, Local
9.
Melanoma Res ; 34(4): 307-318, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38768442

ABSTRACT

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.


Subject(s)
Dog Diseases , Interleukin-2 , Melanoma , Dogs , Animals , Melanoma/radiotherapy , Melanoma/immunology , Melanoma/pathology , Dog Diseases/radiotherapy , Dog Diseases/immunology , Skin Neoplasms/radiotherapy , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Female , Male
10.
Sci Rep ; 14(1): 12363, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38811596

ABSTRACT

Radiotherapy is the standard treatment for glioblastoma (GBM), but the overall survival rate for radiotherapy treated GBM patients is poor. The use of adjuvant and concomitant temozolomide (TMZ) improves the outcome; however, the effectiveness of this treatment varies according to MGMT levels. Herein, we evaluated whether MGMT expression affected the radioresponse of human GBM, GBM stem-like cells (GSCs), and melanoma. Our results indicated a correlation between MGMT promoter methylation status and MGMT expression. MGMT-producing cell lines ACPK1, GBMJ1, A375, and MM415 displayed enhanced radiosensitivity when MGMT was silenced using siRNA or when inhibited by lomeguatrib, whereas the OSU61, NSC11, WM852, and WM266-4 cell lines, which do not normally produce MGMT, displayed reduced radiosensitivity when MGMT was overexpressed. Mechanistically lomeguatrib prolonged radiation-induced γH2AX retention in MGMT-producing cells without specific cell cycle changes, suggesting that lomeguatrib-induced radiosensitization in these cells is due to radiation-induced DNA double-stranded break (DSB) repair inhibition. The DNA-DSB repair inhibition resulted in cell death via mitotic catastrophe in MGMT-producing cells. Overall, our results demonstrate that MGMT expression regulates radioresponse in GBM, GSC, and melanoma, implying a role for MGMT as a target for radiosensitization.


Subject(s)
DNA Modification Methylases , DNA Repair Enzymes , Glioblastoma , Melanoma , Radiation Tolerance , Tumor Suppressor Proteins , Humans , Glioblastoma/genetics , Glioblastoma/radiotherapy , Glioblastoma/metabolism , Glioblastoma/pathology , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Melanoma/radiotherapy , DNA Modification Methylases/metabolism , DNA Modification Methylases/genetics , Cell Line, Tumor , Radiation Tolerance/genetics , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/radiation effects , Neoplastic Stem Cells/pathology , Promoter Regions, Genetic , DNA Methylation , DNA Repair , DNA Breaks, Double-Stranded/radiation effects , Gene Expression Regulation, Neoplastic , Temozolomide/pharmacology , Brain Neoplasms/genetics , Brain Neoplasms/radiotherapy , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Purines
11.
Adv Sci (Weinh) ; 11(26): e2403107, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38704679

ABSTRACT

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.


Subject(s)
Lactic Acid , Melanoma , Reactive Oxygen Species , Tumor Microenvironment , Reactive Oxygen Species/metabolism , Humans , Lactic Acid/metabolism , Melanoma/metabolism , Melanoma/radiotherapy , Tumor Microenvironment/drug effects , Uveal Neoplasms/metabolism , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/genetics , Cell Line, Tumor , Nanostructures/therapeutic use , Mice , Animals , Disease Models, Animal
12.
Brachytherapy ; 23(4): 463-469, 2024.
Article in English | MEDLINE | ID: mdl-38811275

ABSTRACT

INTRODUCTION: Iodine-125 (I-125) seeds, commonly used in low-dose rate brachytherapy for ocular malignancies, are often discarded after a single use. This study examines the potential cost savings at an institution with high ocular melanoma referrals, by re-using I-125 seeds for eye-plaque brachytherapy. METHODS: In this single-institutional retrospective analysis, data was collected from I-125 seed orders from 8/2019 through 10/2022. Information including number of seeds ordered per lot, number of plaques built per lot, and number of seeds used per lot were collected. Cost per lot of seed was assumed to be the current cost from the most recent lot of 35 seeds. RESULTS: During the study, 72 I-125 seed lots were ordered bi-weekly, with a median of 35 seeds per lot (Range: 15-35). Each seed was used on average 2.26 times prior to being discarded. The average duration of each seed lot used was 62.2 days (Range: 21-126). Each seed lot contributed to the construction of an average of 8.4 eye plaques (Range: 2-20). With seed recycling, 2,475 seeds were used to construct 608 eye-plaques. Without re-using practice this would require 5,694 seeds. This resulted in a percentage cost savings of 56.5%, with a total seed cost reduction of $344,884, or $559 per eye-plaque on average. CONCLUSION: This is the first study to evaluate cost savings relative to re-using I-125 seeds for eye plaques. The data demonstrates how an institution can decrease costs associated with I-125 radiation seeds used for eye-plaque brachytherapy by re-using them.


Subject(s)
Brachytherapy , Cost Savings , Eye Neoplasms , Iodine Radioisotopes , Melanoma , Brachytherapy/economics , Iodine Radioisotopes/therapeutic use , Humans , Retrospective Studies , Melanoma/radiotherapy , Melanoma/economics , Eye Neoplasms/radiotherapy , Eye Neoplasms/economics
13.
Eye (Lond) ; 38(10): 1882-1890, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38565600

ABSTRACT

BACKGROUND: Uveal melanoma (UM) is the most common primary ocular tumour in adults. The most used eye-preserving treatments are charged-particle therapy (CPT) and brachytherapy. We performed a systematic review and meta-analysis to compare efficacies and complications of these two radiotherapies. METHODS: We searched EMBASE, PubMed, MEDLINE, and the Cochrane Library from January 2012 to December 2022. Two independent reviewers identified controlled studies comparing outcomes of CPT versus brachytherapy. Case series that utilize either treatment modality were also reviewed. RESULTS: One hundred fifty studies met the eligibility criteria, including 2 randomized control trials, 5 controlled cohort studies, and 143 case series studies. We found significant reduction in local recurrence rate among patients treated with CPT compared to brachytherapy (Odds ratio[OR] 0.38, 95% Confidence interval [CI] 0.24-0.60, p < 0.01). Analysis also showed a trend of increased risks of secondary glaucoma after CPT. No statistically significant differences were found in analyzing risks of mortality, enucleation, and cataract. CONCLUSIONS: Our study suggested no difference in mortality, enucleation rate and cataract formation rate comparing the two treatments. Lower local recurrence rate and possibly higher secondary glaucoma incidence was noted among patients treated with CPT. Nevertheless, the overall level of evidence is limited, and further high-quality studies are necessary to provide a more definitive conclusion.


Subject(s)
Brachytherapy , Melanoma , Uveal Neoplasms , Humans , Brachytherapy/methods , Brachytherapy/adverse effects , Uveal Neoplasms/radiotherapy , Melanoma/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Treatment Outcome
14.
Can Vet J ; 65(4): 343-350, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562982

ABSTRACT

Background: Effective treatment for canine oral malignant melanoma (e.g., curative-intent surgery) may not be feasible or radiation therapy may be unavailable. However, chemotherapy is usually an option, and more information is needed regarding its use without adequate local treatments. Objective: Our objective was to investigate the efficacy of chemotherapy in canine oral malignant melanoma without adequate local control, using carboplatin with dose reduction in small-breed dogs and metronomic chemotherapy. Animals and procedure: Client-owned dogs with histopathologically diagnosed oral malignant melanoma were retrospectively enrolled from 2016 to 2022. The chemotherapy protocol in each case was determined by the attending clinician. Results: Thirteen dogs were included. The median progression-free interval of all 13 dogs was 42 d (14 to 953 d). The median overall survival time of dogs with chemotherapy as their only systemic treatment was 181 d (50 to 960 d; n = 11). The median dosage of carboplatin was 250 mg/m2. Response to treatment and clinical stage were significant prognostic factors. Conclusion and clinical relevance: As chemotherapy provided a median survival of 6 mo, it could be considered when adequate local control is infeasible. Earlier clinical stages or achievement of at least stable disease during chemotherapy may indicate better survival in dogs.


Une étude rétrospective de l'effet chimiothérapeutique sur le mélanome malin buccal canin dépourvu de chirurgie et de radiothérapie á large marge : le stade clinique et la réponse au traitement prédisent les résultats du patient. Mise en contexte: Des traitements efficaces pour le mélanome malin oral canin, tels que la chirurgie á visée curative, ne sont parfois pas réalisables ou la radiothérapie n'est pas disponible dans certaines régions. La chimiothérapie reste une option de traitement et davantage d'informations devraient être fournies pour les cas qui n'ont pas eu accés á un traitement local adéquat. Objectif: Cette étude visait á étudier l'efficacité de la chimiothérapie dans le mélanome malin oral canin sans contrôle local adéquat, en utilisant le carboplatine avec réduction de dose chez les chiens de petite race et la chimiothérapie métronomique. Animaux et procédure: Treize chiens appartenant á des clients atteints d'un mélanome malin oral diagnostiqué par histopathologie ont été rétrospectivement inscrits de 2016 á 2022. Le protocole de chimiothérapie a été déterminé par le clinicien traitant. Résultats: L'intervalle médian sans progression des treize chiens était de 42 jours (14­953 jours). La durée médiane de survie globale des chiens ayant reçu une chimiothérapie comme seul traitement systémique était de 181 jours (50­960 jours; n = 11). La dose médiane de carboplatine était de 250 mg/m2. La réponse au traitement et le stade clinique étaient des facteurs pronostiques importants. Conclusion et pertinence clinique: La chimiothérapie pouvait encore être envisagée lorsqu'un contrôle local adéquat était impossible. Des stades cliniques plus précoces ou des patients atteignant au moins une maladie stable pendant la chimiothérapie peuvent indiquer une meilleure survie.(Traduit par les auteurs).


Subject(s)
Antineoplastic Agents , Dog Diseases , Melanoma , Mouth Neoplasms , Skin Neoplasms , Humans , Dogs , Animals , Melanoma/drug therapy , Melanoma/radiotherapy , Melanoma/veterinary , Carboplatin/therapeutic use , Retrospective Studies , Antineoplastic Agents/therapeutic use , Mouth Neoplasms/drug therapy , Mouth Neoplasms/radiotherapy , Mouth Neoplasms/surgery , Mouth Neoplasms/veterinary , Dog Diseases/drug therapy , Dog Diseases/radiotherapy , Dog Diseases/surgery , Skin Neoplasms/veterinary
15.
J Appl Clin Med Phys ; 25(7): e14362, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38669175

ABSTRACT

PURPOSE: Proton stereotactic radiosurgery (PSRS) has emerged as an innovative proton therapy modality aimed at achieving precise dose delivery with minimal impact on healthy tissues. This study explores the dosimetric outcomes of PSRS in comparison to traditional intensity-modulated proton therapy (IMPT) by focusing on cases with small target volumes. A custom-made aperture system designed for proton therapy, specifically tailored to small target volumes, was developed and implemented for this investigation. METHODS: A prerequisite mechanical validation through an isocentricity test precedes dosimetric assessments, ensuring the seamless integration of mechanical and dosimetry analyses. Five patients were enrolled in the study, including two with choroid melanoma and three with arteriovenous malformations (AVM). Two treatment plans were meticulously executed for each patient, one utilizing a collimated aperture and the other without. Both plans were subjected to robust optimization, maintaining identical beam arrangements and consistent optimization parameters to account for setup errors of 2 mm and range uncertainties of 3.5%. Plan evaluation metrics encompassing the Heterogeneity Index (HI), Paddick Conformity Index (CIPaddick), Gradient Index (GI), and the R50% index to evaluate alterations in low-dose volume distribution. RESULTS: The comparative analysis between PSRS and traditional PBS treatment revealed no significant differences in plan outcomes, with both modalities demonstrating comparable target coverage. However, collimated apertures resulted in discernible improvements in dose conformity, dose fall-off, and reduced low-dose volume. CONCLUSIONS: This study underscores the advantageous impact of the aperture system on proton therapy, particularly in cases involving small target volumes.


Subject(s)
Organs at Risk , Proton Therapy , Radiosurgery , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Planning, Computer-Assisted/methods , Radiosurgery/methods , Proton Therapy/methods , Radiotherapy, Intensity-Modulated/methods , Organs at Risk/radiation effects , Melanoma/radiotherapy , Melanoma/surgery
16.
Klin Monbl Augenheilkd ; 241(4): 421-425, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38653304

ABSTRACT

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions. CASE PRESENTATION: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed. CONCLUSION: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient's complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.


Subject(s)
Radiation Injuries , Humans , Female , Adult , Radiation Injuries/etiology , Radiation Injuries/surgery , Melanoma/surgery , Melanoma/radiotherapy , Corneal Diseases/etiology , Corneal Diseases/surgery , Treatment Outcome , Iris Neoplasms/radiotherapy , Iris Neoplasms/surgery , Proton Therapy/adverse effects , Keratoplasty, Penetrating/adverse effects
17.
In Vivo ; 38(3): 1220-1228, 2024.
Article in English | MEDLINE | ID: mdl-38688652

ABSTRACT

BACKGROUND/AIM: Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. PATIENTS AND METHODS: All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). RESULTS: On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. CONCLUSION: GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.


Subject(s)
Melanoma , Meningeal Neoplasms , Humans , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/pathology , Meningeal Neoplasms/mortality , Female , Male , Melanoma/radiotherapy , Melanoma/pathology , Melanoma/mortality , Middle Aged , Adult , Aged , Combined Modality Therapy , Treatment Outcome , Adolescent
18.
Am J Ophthalmol ; 262: 161-169, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38307213

ABSTRACT

PURPOSE: To determine the incidence and type of strabismus in patients with uveal melanoma treated with plaque brachytherapy. DESIGN: Multicenter, retrospective incidence estimation study. METHODS: A total of 438 eyes of 438 patients with uveal melanoma treated with plaque brachytherapy between October 2011 and May 2021. Intervention was Iodine 125, and Palladium 103 plaque brachytherapy. The variables reviewed included incidence of nonresolving strabismus post-plaque brachytherapy, type of strabismus developed, extraocular muscles operated, and modality of treatment received. RESULTS: A total of 438 patients underwent plaque brachytherapy treatment for uveal melanoma. Eleven patients developed strabismus post-plaque brachytherapy (2.5%, n = 11/438). Of these patients, 5 (1.1%, n = 5/438) developed strabismus immediately postoperation. Specifically, 2 patients (0.5%, n = 2/438) developed strabismus immediately postoperation due to slipped muscles, 2 patients (0.5%, n = 2/438) due to decompensated phorias, and 1 patient (0.5%, n = 1/438) due to a fibrotic muscle. Six patients (1.4%, n = 6/438) developed late-onset sensory strabismus. A total of 355 patients (81.1%, n = 355/438) had their extraocular muscles disinserted during surgery, with the lateral rectus being the most common, accounting for 45.4% (n = 161/355), followed by the superior rectus at 26.8% (n = 95/355). Strabismus surgery was the most common treatment modality, comprising 72.7% (n = 8/11) of patients. CONCLUSIONS: The incidence of strabismus after plaque brachytherapy treatment for uveal melanoma was low and primarily classified as late-onset sensory strabismus. Previous studies may underestimate the long-term incidence of strabismus after plaque brachytherapy by focusing primarily on strabismus present immediately postoperatively.


Subject(s)
Brachytherapy , Iodine Radioisotopes , Melanoma , Strabismus , Uveal Neoplasms , Humans , Brachytherapy/adverse effects , Melanoma/radiotherapy , Melanoma/epidemiology , Strabismus/etiology , Strabismus/epidemiology , Incidence , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/epidemiology , Retrospective Studies , Male , Female , Middle Aged , Aged , Iodine Radioisotopes/therapeutic use , Iodine Radioisotopes/adverse effects , Adult , Aged, 80 and over , Oculomotor Muscles/radiation effects , Oculomotor Muscles/surgery , Palladium/therapeutic use , Radioisotopes/therapeutic use , Radiation Injuries/etiology , Radiation Injuries/epidemiology
19.
Brachytherapy ; 23(3): 377-386, 2024.
Article in English | MEDLINE | ID: mdl-38336557

ABSTRACT

PURPOSE: To provide a practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo (MC) calculation in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques. METHODS AND MATERIALS: Using egs_brachy, MC simulations (1) under task group-43 assumptions with fully loaded seed configurations in water (HOMO) and (2) with effects of plaque backing, insert and inter-seed interactions (HETERO) were performed for seven 125I COMS plaques (10 mm-22 mm in diameter), and homogeneous dose (DHOMO) and heterogeneous dose (DHETERO) for central-axis and off-axis points were determined. For DHOMO, 85 Gy was normalized to a depth of 5 mm. Central-axis heterogeneity correction factors (HCFs) from a depth of 0 mm (inner sclera) to 22 mm (opposite retina) were derived from a ratio of DHETERO to DHOMO. Off-axis HCFs for optic disc/macula and lens as a function of distance from optic disc/macula (DT/MT) for various basal dimensions of tumor (BD/BM) were derived from DHETERO/DHOMO. RESULTS: Central-axis HCF varied with a dose reduction of 10.3-19.8% by heterogeneity. Off-axis HCF for optic disc/macula varied significantly depending on DT/MT and BD/BM with a dose reduction of 11.3-38.3%. Off-axis HCF for lens had a dependence on MT and BM with its variation of 11.0-19.0%. A clinical example of using HCFs to estimate DHETERO was presented. CONCLUSIONS: The practical method of using depth-dependent central-axis HCF and DT/MT- and BD/BM-dependent off-axis HCF provided in this study will facilitate a heterogeneous dose estimate for 125I COMS plaques without MC calculations.


Subject(s)
Brachytherapy , Eye Neoplasms , Iodine Radioisotopes , Melanoma , Monte Carlo Method , Radiotherapy Dosage , Brachytherapy/methods , Humans , Iodine Radioisotopes/therapeutic use , Melanoma/radiotherapy , Eye Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods
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