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1.
Lancet Oncol ; 21(11): 1526-1536, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152286

RESUMO

BACKGROUND: Gamma knife radiosurgery is regarded as the gold-standard stereotactic radiosurgery modality for the treatment of intracranial tumours, and its use has been expanded for the treatment of intraocular malignancies. The aim of this study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife radiosurgery for uveal melanomas and metastases. METHODS: We did a systematic review and meta-analysis to aggregate the clinical outcomes of patients with uveal melanomas or intraocular metastases treated primarily with gamma knife radiosurgery. We searched MEDLINE and Embase for studies published between Sept 1, 1960, and Feb 1, 2020, reporting the use of gamma knife radiosurgery as primary treatment for uveal melanoma or uveal metastases. The search was restricted to clinical studies and relevant grey literature published in English. Studies reporting treatment of benign tumours, extraocular tumours, or other forms of stereotactic radiosurgery were excluded to reduce heterogeneity. No restrictions were placed on participant criteria. Local tumour control and tumour regression were extracted as the primary outcomes and analysed via a random-effects meta-analysis of proportions using the DerSimonian and Laird method with a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42019148165. FINDINGS: Our search returned 454 studies, of which 109 were assessed for full-text eligibility. 52 studies, reporting on 1010 patients with uveal melanoma and 34 intraocular metastases, were eligible for systematic review. 28 studies were included in the meta-analysis. 840 of 898 patients (0·96, 95% CI 0·94-0·97; I2=16%) from 19 studies had local control, and 378 of 478 patients (0·81, 0·70-0·90; I2=83%) from 16 studies experienced tumour regression. INTERPRETATION: Gamma knife radiosurgery is an efficacious primary method of treating uveal melanomas and intraocular metastases, with reliable tumour control rates. Randomised controlled trials should further evaluate the safety and efficacy of gamma knife radiosurgery in this setting. FUNDING: The Rhodes Trust and the Howard Brain Sciences Foundation.


Assuntos
Melanoma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Neoplasias Uveais/cirurgia , Humanos , Melanoma/patologia , Melanoma/radioterapia , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia/efeitos adversos , Resultado do Tratamento , Neoplasias Uveais/patologia , Neoplasias Uveais/radioterapia
2.
Zhonghua Yan Ke Za Zhi ; 56(9): 670-675, 2020 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-32907299

RESUMO

Objective: To investigate the safety and efficacy of external scleral plaque radiotherapy (PRT) in the treatment of uveal melanoma (UM). Methods: This was a retrospective case series study. The data of 819 patients who underwent ophthalmic PRT from July 2007 to November 2017 at Tongren Hospital Affiliated to Beijing Capital Medical University was collected, including preoperative visual acuity, intraocular pressure and slit lamp microscope, color fundus photography, indirect ophthalmoscopy, color Doppler ultrasound, fundus fluorescein angiography, indocyanine green angiography, orbital nuclear magnetic resonance imaging, PRT times and time, complications, follow-up time, the maximum basal diameter and height of the tumor UM half a year after the applicator was removed, tumor metastasis rate, mortality and visual acuity observed at the last follow-up. The tumor growth was considered when the tumor height increased by 2.0 mm or the extension of any boundary of the tumor was 2.5 mm; otherwise, the treatment was defined as effective. The paired t test and Kaplan-Meier survival curve were used for statistical analysis. Results: There were 408 males and 411 females. The age ranged from 13 to 85 years (mean, 47 years). Nine patients had ciliary body melanoma, 43 patients had choroidal melanoma involving the ciliary body, and 767 patients had choroidal melanoma. In all 819 eyes, the tumor was medium-sized in 697 eyes and large in 110 eyes. All patients were treated with PRT only one time. The average radiotherapy time was 15 days (range, 6 to 50 d). All operations were successfully completed, with no active bleeding, infection, adjacent tissue injury and other related complications. At 6 months after the treatment, the maximum basal diameter of the tumor was (12.41±3.20) mm, which was significantly different from that before treatment (12.82±3.21) mm (t=2.40, P<0.01); the tumor height was (6.18±2.55) mm, which was significantly different from that before treatment (7.21±2.57) mm (t=4.05, P<0.01). The average follow-up time was (34±24) months (range, 1 to 125 months). Twenty-five patients lost follow-up at 2 years after the PRT, and 71 patients underwent enucleation. The effective rate of the PRT treatment was 88.3% (723/819), and the eyeball retention rate was 91.1% (723/794). The visual acuity remained stable in 393 eyes, decreased in 344 eyes, and improved in 82 eyes. Sixty patients had systemic metastasis (liver, bone or breast metastasis). Twenty-two patients died of tumor metastasis. The 5-year metastasis rate was 12.8%; the 5-year mortality rate was 5.8%; the 10-year metastasis rate was 20.6%; the 10-year mortality rate was 5.8%. Conclusions: PRT is safe and effective in the treatment for UM and can preserve some useful visual acuity. PRT can be used as the main treatment for medium-sized UM.(Chin J Ophthalmol, 2020, 56: 670-675).


Assuntos
Braquiterapia , Melanoma/radioterapia , Neoplasias Uveais/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Cesk Slov Oftalmol ; 76(1): 46-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32917094

RESUMO

INTRODUCTION: In the past enucleation was the treatment of choice for all the patients with uveal melanoma. Nowadays, we prefer glope-sparing treatment modalities, except for large tumors, tumors with extrascleral extension and painful blind eyes. Most of the patients perform radiotherapy or local resection techniques. In Slovak Republic, the only one possibility is a stereotactic radiotherapy on a linear accelerator LINAC. Nevertheless, enucleation after radiotherapy is necessary for some patients. The causes are postradiation complications, mainly neovascular glaucoma, tumor recurrence, tumor progression or patient´s decision. MATERIAL AND METHODS: The retrospective non-randomised study of 168 eyes of the patients with choroidal or ciliary body melanoma, who performed one-day session stereotactic radiosurgery at the linear accelerator LINAC during period 2007-2016. The data about postradiation complications were analysed based on the medical records of the patients and the data about enucleated eyes based on the histopathological findings. RESULTS: The occurence of enucleation after radiotherapy in our cohort was 17 % (28 patients), with median time period after radiotherapy 21,5 months. The most common cause was neovascular glaucoma (82 %), then tumor progression (14 %) and patient´s decision (4 %). The most common histopathological finding was spindle-cell melanoma. DISCUSSION: Others authors describe similar enucleation rate and causes. The histopathological findings indentified more viable melanoma cells in eyes enucleated for tumor progression in comparison with enucleation for other causes. Enucleation may be more difficult and the occurence of postoperative complications can be higher in the eyes after radiotherapy rather than primary enucleation. CONCLUSION: The management of the patients with uveal melanoma is difficult, and requires the cooperation of ophthalmologist, oncologist, radiation physicist and pathologist. Even if we make effort to preserve the eye, enucleation after radiotherapy is necessary in some patients.


Assuntos
Melanoma , Radiocirurgia , Neoplasias Uveais , Humanos , Melanoma/radioterapia , Melanoma/cirurgia , Estudos Retrospectivos , Eslováquia , Resultado do Tratamento , Neoplasias Uveais/radioterapia , Neoplasias Uveais/cirurgia
4.
Cancer Immunol Immunother ; 69(9): 1823-1832, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350591

RESUMO

Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metastases did not regress and new metastases occurred although neoepitope-specific and differentiation antigen-specific CD8+ T cells were detected in the blood. A second SBRT after 10 months on anti-PD-1 induced a radiologic complete response correlating with an increase in activated PD-1-expressing CD8 T cells. Apart from a new lung lesion, which was also irradiated, this deep abscopal response lasted for more than 2.5 years. However, thereafter, his disease progressed and the activated PD-1-expressing CD8 T cells dropped. Our data suggest that oligometastatic patients, where a large proportion of the tumor mass can be irradiated, are good candidates to improve ICB responses by RT, even in the case of an unfavorable pretreatment immune signature, after progression on anti-PD-1, and despite advanced age. Besides repeated irradiation, T cell epitope-based immunotherapies (e.g., vaccination) may prolong antitumor responses even in patients with unfavorable pretreatment immune signature.


Assuntos
Melanoma/imunologia , Melanoma/radioterapia , Receptor de Morte Celular Programada 1/imunologia , Idoso , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Melanoma/terapia , Radiocirurgia/métodos
5.
J Cancer Res Ther ; 16(1): 189-191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362637

RESUMO

Coexistence of malignant melanoma and renal cell cancer (RCC) is a rare phenomenon, but this issue becomes increasingly popular. The objective of the current study is to present a case with coexistent anorectal melanoma (ANM) and papillary RCC detected. A 61-year-old female admitted to our clinic with complaints of blood in the stool. ANM diagnosed with colonoscopic biopsy and a mass lession with a size of 57 mm × 53 mm suggesting RCC was detected in the left kidney during staging procedure. Transabdominal resection and radical nephrectomy were performed and diagnoses of ANM and papillary RCC were confirmed. Adjuvant radiotherapy was applied for ANM. The patient is still under follow-up for 6 months and no recurrence or progression was detected. To the best of our knowledge, this is the first report of this interesting coexistency.


Assuntos
Neoplasias do Ânus/patologia , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Melanoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/patologia , Neoplasias do Ânus/radioterapia , Carcinoma Papilar/radioterapia , Carcinoma de Células Renais/radioterapia , Feminino , Humanos , Neoplasias Renais/radioterapia , Melanoma/radioterapia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/radioterapia , Prognóstico , Neoplasias Cutâneas/radioterapia
6.
Am J Ophthalmol ; 216: 165-173, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278771

RESUMO

PURPOSE: To assess efficacy of intravitreal ranibizumab injections and targeted panretinal photocoagulation (TRP) for radiation retinopathy-related macular edema. DESIGN: Phase IIb, prospective, randomized clinical trial. METHODS: Setting: Multicenter. SUBJECTS: Forty eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen equivalent). INTERVENTION: Patients either received intravitreal 0.5 mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MainOutcomeMeasures: Mean Early Treatment Diabetic Maculopathy Study (ETDRS) BCVA change from baseline. RESULTS: Mean patient age was 57 years (range, 22-80 years), ETDRS BCVA was 56.7 letters (20/74 Snellen equivalent), and central macular thickness (CMT) was 423 µm (range, 183-826 µm). Thirty-seven patients completed the month 12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters, and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all 3 cohorts (P < .001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. A total of 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters. CONCLUSIONS: Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Edema Macular/tratamento farmacológico , Melanoma/radioterapia , Lesões por Radiação/tratamento farmacológico , Radioterapia/efeitos adversos , Ranibizumab/administração & dosagem , Retina/efeitos da radiação , Neoplasias Uveais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Injeções Intravítreas , Fotocoagulação a Laser , Edema Macular/diagnóstico por imagem , Edema Macular/etiologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Adulto Jovem
8.
Oncology ; 98(4): 202-215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32079015

RESUMO

BACKGROUND: Malignant melanoma represents the deadliest form of skin cancer with a high tendency to metastasize during the early course of the disease. Radiation therapy has long played a key role in the management of both local and metastatic melanoma. Although local radiation therapy exerts antitumor effects by damaging the cellular DNA, it also induces an important out-of-field (distant) effect known as the "abscopal effect" in nonirradiated sites. Radiation therapy-induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. OBJECTIVE: To provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with malignant melanoma. METHODS: Using electronic databases such as MEDLINE via PubMed and Google Scholar, a systematic literature review was performed to find published clinical evidence for radiation therapy-induced abscopal effects in patients with malignant melanoma. The clinical data on radiation therapy-induced abscopal effects were reviewed and the outcomes summarized. RESULTS: Clinical evidence of patients with malignant melanoma was gathered using databases from MEDLINE and those findings were summarized. Although the precise mechanism of the abscopal effect of radiation therapy is still not completely understood, evidence suggests that tumor cell destruction by radiation releases tumor antigens that stimulate the immune system of the host to activate the body's immune effector cells systemically and produce distant non-target antitumor effects. This forms a basis for using the radiation therapy with immunotherapy to augment the abscopal response rates. CONCLUSIONS: Current clinical evidence suggests that there is a large potential to enhance the abscopal effect when radiation therapy is combined with immunotherapeutic agents for the treatment of malignant melanoma. Ongoing and planned clinical trials may provide us with a more in-depth understanding of how this combination therapy can be optimally utilized clinically to achieve improved survival outcomes among patients with malignant melanoma.


Assuntos
Efeito Espectador , Sistema Imunitário/efeitos da radiação , Melanoma/radioterapia , Humanos
10.
Asia Pac J Ophthalmol (Phila) ; 9(1): 29-38, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990743

RESUMO

PURPOSE: The aim of this study was to determine the impact of age on radiation complications after plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma. DESIGN: Retrospective cohort study. METHODS: Retrospective single-center study of plaque-irradiated uveal melanoma with prophylactic intravitreal bevacizumab at 4-month intervals from July 2000 to January 2018. RESULTS: Of 1131 eyes in 1131 patients, age was <50 years (n = 231), 50 to 70 years (n = 657), or >70 years (n = 243). Comparison by age category (<50 vs 50-70 vs >70 years) revealed the oldest group presenting with greatest tumor basal diameter (11.3 vs 11.3 vs 12.1 mm, P = 0.03) and worst visual acuity (20/40 vs 20/40 vs 20/50, P = 0.02). After plaque (mean follow-up 40 vs 42 vs 32 months, P < 0.001), radiation complications were most common in the youngest age group, including maculopathy (48% vs 39% vs 28%, P < 0.001), extramacular retinopathy (30% vs 25% vs 16%, P = 0.002), and papillopathy (21% vs 18% vs 12%, P = 0.03). The youngest age group had the highest Kaplan-Meier estimated 48-month cumulative probability for radiation maculopathy (62% vs 46% vs 47%, P = 0.001), extramacular retinopathy (36% vs 34% vs 29%, P = 0.03), and papillopathy (29% vs 26% vs 22%, P = 0.13). On subanalysis, the youngest age group had increased 48-month risk of developing radiation maculopathy when compared with the middle [hazard ratio (HR) = 1.5, P = 0.001] and older (HR = 1.6, P = 0.005) age groups and increased 48-month risk of developing extramacular radiation retinopathy compared with the older age group (HR = 1.5, P = 0.04). CONCLUSIONS: After plaque radiotherapy for uveal melanoma and prophylactic intravitreal bevacizumab at 4-month intervals, patients younger than 50 years old have an increased 48-month risk of radiation maculopathy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Braquiterapia , Melanoma/radioterapia , Lesões por Radiação/prevenção & controle , Doenças Retinianas/prevenção & controle , Neoplasias Uveais/radioterapia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Radioisótopos do Iodo/uso terapêutico , Edema Macular/fisiopatologia , Edema Macular/prevenção & controle , Masculino , Melanoma/tratamento farmacológico , Melanoma/fisiopatologia , Pessoa de Meia-Idade , Lesões por Radiação/fisiopatologia , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
11.
Clin Ter ; 170(1): e89-e98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31916427

RESUMO

Introduction: Uveal melanoma is the most common intraocular tumor in the adult population. It can affect any part of the uveal tract: the iris, ciliary body, and choroid. Historically, enucleation has been the mainstay of treatment for primary melanoma. In the last decade, however, radiotherapy has acquired an increasingly important role and has now become our first-line modality. However, it is still widely debated what is the most effective radiotherapy technique for this tumor. Purpose to perform a literature review on the utility of radiotherapy for primary ocular melanoma and determine the most effective radiotherapy technique Materials and Methods: We included all systematic and narrative reviews on the topic, published between September 2007 and November 2017 on PubMed and SCOPUS. Two independent reviewers assessed the eligibility criteria for each article using the PRISMA checklist. The methodological quality of narrative and systematic reviews was evaluated with the INSA and AMSTAR checklists, respectively Results: Our study analyzed a total of 23 studies, including 18 narrative reviews and 5 systematic reviews. Radiotherapy with Brachytherapy, Proton Therapy, SRS/SRT with gamma knife and cyber knife, are the most common choices for the treatment of primary ocular melanoma. These techniques allow for excellent lesion spread control, eye, and vision conservation, and improve overall patients' quality of life. Among the narrative reviews, the highest INSA score was 5/7, the lowest 2/7, the mean was 3.83/7 and median was 4/7. Among the systematic reviews, the highest AMSTAR score was 9/12, the lowest 4/12, the mean 5.6/7 and median 4/7 Conclusion: The number of studies available on this topic is scarce. Among those published, the methodological quality is modest, as assessed with the INSA and AMSTAR checklists. As a result, we are not able to determine what the most effective radiotherapy technique is


Assuntos
Neoplasias Oculares/radioterapia , Melanoma/radioterapia , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Radioterapia/métodos , Radioterapia/estatística & dados numéricos , Doenças da Úvea/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
JAMA Ophthalmol ; 138(3): 260-267, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31944225

RESUMO

Importance: The Cancer Genome Atlas (TCGA) classification is a newly emerging method for prediction of uveal melanoma (UM)-related metastasis and death. Limited information is available regarding the accuracy of the TCGA classification for prediction of metastasis in patients with UM. Objective: To investigate the accuracy of the TCGA classification for predicting UM-related metastasis compared with the American Joint Committee on Cancer (AJCC) classification. Design, Setting, and Participants: In this retrospective cohort study, patients with UM treated with plaque radiotherapy at a tertiary referral center from October 1, 2008, to December 31, 2018, were evaluated. All patients with tumors classified according to the American Joint Committee on Cancer Staging Manual, 8th Edition, and who completed pretreatment fine-needle aspiration biopsy sampling for genetic analysis of chromosomes 3 and 8 for TCGA classification were included. Tumors were classified into 4 categories, 17 subcategories, and 4 stages using AJCC classification and further grouped into 4 classes using TCGA classification. Main Outcomes and Measures: Value of TCGA classification vs AJCC classification for predicting UM-related metastasis. Results: Of 642 included patients, 331 (51.6%) were women, and the mean (SD) age was 58.0 (13.8) years. There were 642 tumors from 642 patients classified according to both AJCC and TCGA classifications. The mean (range) follow-up time for the entire cohort was 43.7 (1.4-159.2) months. At 5 years, TCGA classification showed higher value for prediction of metastasis (4 TCGA classes: Wald statistic, 94.8; hazard ratio [HR], 2.8; 95% CI, 2.3-3.5; P < .001; 4 AJCC categories: Wald statistic, 67.5; HR, 2.6; 95% CI, 2.1-3.2; P < .001; 17 AJCC subcategories: Wald statistic, 74.3; HR, 1.3; 95% CI, 1.2-1.3; P < .001; 4 AJCC stages: Wald statistic, 67.0; HR, not applicable; P < .001). After entering TCGA and AJCC classifications into a multivariate model, TCGA classification still showed higher value for prediction of metastasis (TCGA classification: Wald statistic, 61.5; HR, 2.4; 95% CI, 1.9-2.9; P < .001; AJCC classification: Wald statistic, 35.5; HR, 1.9; 95% CI, 1.5-2.4; P < .001). Conclusions and Relevance: These results suggest that TCGA classification provides accuracy that is superior to AJCC categories, subcategories, and stages for predicting metastasis from UM. When genetic testing is available, TCGA classification can provide a more accurate way to identify patients at high risk of metastasis who might benefit from adjuvant therapy.


Assuntos
Melanoma/secundário , Estadiamento de Neoplasias , Neoplasias Uveais/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Braquiterapia , Feminino , Humanos , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/radioterapia , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Neoplasias Uveais/genética , Neoplasias Uveais/mortalidade , Neoplasias Uveais/radioterapia
14.
In Vivo ; 34(1): 381-387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882502

RESUMO

AIM: The aim of this study was to detect clinical factors predictive of loss of visual acuity after treatment in order to develop a predictive model to help identify patients at risk of visual loss. PATIENTS AND METHODS: This was a retrospective review of patients who underwent interventional radiotherapy (brachytherapy) with 106Ru plaque for primary uveal melanoma. A predictive nomogram for visual acuity loss at 3 years from treatment was developed. RESULTS: A total of 152 patients were selected for the study. The actuarial probability of conservation of 20/40 vision or better was 0.74 at 1 year, 0.59 at 3 years, and 0.54 at 5 years after treatment. Factors positively correlated with loss of visual acuity included: age at start of treatment (p=0.004) and longitudinal basal diameter (p=0.057), while distance of the posterior margin of the tumor from the foveola was inversely correlated (p=0.0007). CONCLUSION: We identified risk factors affecting visual function and developed a predictive model and decision support tool (AVATAR nomogram).


Assuntos
Braquiterapia/métodos , Neoplasias da Coroide/radioterapia , Melanoma/radioterapia , Nomogramas , Radioisótopos de Rutênio/uso terapêutico , Neoplasias Uveais/radioterapia , Acuidade Visual/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/patologia , Feminino , Seguimentos , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Uveais/patologia , Acuidade Visual/efeitos da radiação , Adulto Jovem
16.
Biochem Biophys Res Commun ; 522(3): 639-646, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31785810

RESUMO

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Despite of important progress in the local therapy, high radioresistance in primary tumor and chemoresistance in metastatic disease are the major obstacles for UM therapy. Therefore, strategies to overcome resistance to radiation or chemotherapy in UM are urgently needed. In this study, we found that phosphorylation of DNA-PKcs, which is the key factor of non-homologous end joining (NHEJ) pathway, was remarkably overexpressed in ionizing radiation (IR)- and Selumetinib resistant UM cells. Increased amount of NHEJ events were also observed in resistant UM cells. Inhibition of DNA-PKcs by NU7441 significantly impaired DNA repair and re-sensitized resistant UM cells to radiation and Selumetinib both in vitro and in vivo. The results demonstrate increased DNA double strand break repair as a mechanism of resistance to ionizing radiation and Selumetinib, and identify DNA-PKcs as a promising target for radio-and chemotherapy in UM patients.


Assuntos
Benzimidazóis/farmacologia , Cromonas/farmacologia , Proteína Quinase Ativada por DNA/antagonistas & inibidores , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Morfolinas/farmacologia , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/radioterapia , Animais , Benzimidazóis/uso terapêutico , Linhagem Celular Tumoral , Cromonas/uso terapêutico , Proteína Quinase Ativada por DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Melanoma/metabolismo , Camundongos Endogâmicos BALB C , Morfolinas/uso terapêutico , Fosforilação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Neoplasias Uveais/metabolismo
17.
Br J Ophthalmol ; 104(1): 26-32, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30910871

RESUMO

BACKGROUND: Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and ß-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope. METHODS: All patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups. RESULTS: 317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5-7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%). CONCLUSIONS: Rates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.


Assuntos
Braquiterapia/métodos , Neoplasias da Coroide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Melanoma/radioterapia , Radioisótopos de Rutênio/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/patologia , Neoplasias da Coroide/cirurgia , Enucleação Ocular/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Adulto Jovem
18.
Oncogene ; 39(10): 2118-2124, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31811271

RESUMO

Uveal melanoma is the most common intraocular primary malignancy in adults and has been considered a fatal disease for decades. Optogenetics is an emerging technique that can control the activation of signaling components via irradiation with visible light. The clinical translation of optogenetics has been limited because of the need for surgical implantation of electrodes and relatively shallow tissue penetration. As visible light easily penetrates the eyes, we hypothesized that an optogenetics approach can be an effective treatment of uveal melanoma without surgery. In this study, we evaluated the feasibility of this strategy by using a genetically encoded optogenetic system based on reversible blue light-induced binding pairs between Fas-CIB1-EGFP and CRY2-mCherry-FADD. Subretinal injection of B16 cells was performed to create a uveal melanoma model. Plasmids pairs were co-transfected into B16 cells. We found that blue light irradiation dynamically controlled the translocation of FADD to Fas on the plasma membrane and induced the apoptosis of B16 cells transfected with the optogenetic nanosystem in vitro. Moreover, the blue light-controlled optogenetic nanosystem suppressed the growth of uveal melanoma in vivo by inducing apoptosis. These results suggest that light-controlled optogenetic therapy can be used as a potential novel therapeutic strategy for uveal melanoma.


Assuntos
Apoptose , Terapia Genética/métodos , Luz , Melanoma/terapia , Optogenética/métodos , Neoplasias Uveais/terapia , Animais , Modelos Animais de Doenças , Feminino , Melanoma/metabolismo , Melanoma/fisiopatologia , Melanoma/radioterapia , Camundongos , Transdução de Sinais , Neoplasias Uveais/metabolismo , Neoplasias Uveais/fisiopatologia , Neoplasias Uveais/radioterapia
19.
Surg Clin North Am ; 100(1): 189-199, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753112

RESUMO

The role of radiation therapy in melanoma has evolved over the last few decades. There has been a dramatic improvement in radiation delivery with the introduction of intensity-modulated radiation therapy, image-guided radiation therapy, stereotactic radiosurgery, and stereotactic body radiation therapy/stereotactic radiation therapy. More recently, with the introduction of immunotherapy in various malignancies, including melanoma, the role of radiation therapy is being reevaluated. This article describes the evolution of the role of radiation therapy from nonimmunotherapy to the era of immunotherapy.


Assuntos
Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Terapia Combinada , Humanos , Imunoterapia , Melanoma/terapia , Neoplasias Cutâneas/terapia
20.
Chem Commun (Camb) ; 56(4): 547-550, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31829350

RESUMO

We report a cancer cell membrane-camouflaged nanoreactor based on a GOx decorated TiO2@MnO2 core-shell structure for enhanced radiotherapy against cancer metastasis. The nanoreactor could specifically target tumor tissues, catalytically oxidize glucose to generate H2O2, and generate abundant ROS under X-ray irradiation.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/secundário , Membrana Celular/efeitos dos fármacos , Compostos de Manganês/farmacologia , Melanoma/radioterapia , Melanoma/secundário , Nanopartículas/química , Óxidos/farmacologia , Titânio/farmacologia , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Compostos de Manganês/química , Melanoma/patologia , Camundongos , Óxidos/química , Tamanho da Partícula , Propriedades de Superfície , Titânio/química , Raios X
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