Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
1.
Cell Rep ; 34(2): 108620, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33440157

RESUMO

Phosphatidylserine (PS) is exposed on the surface of apoptotic cells and is known to promote immunosuppressive signals in the tumor microenvironment (TME). Antibodies that block PS interaction with its receptors have been shown to repolarize the TME into a proinflammatory state. Radiation therapy (RT) is an effective focal treatment of isolated solid tumors but is less effective at controlling metastatic cancers. We found that tumor-directed RT caused an increase in expression of PS on the surface of viable immune infiltrates in mouse B16 melanoma. We hypothesize that PS expression on immune cells may provide negative feedback to immune cells in the TME. Treatment with an antibody that targets PS (mch1N11) enhanced the anti-tumor efficacy of tumor-directed RT and improved overall survival. This combination led to an increase in proinflammatory tumor-associated macrophages. The addition of anti-PD-1 to RT and mch1N11 led to even greater anti-tumor efficacy and overall survival. We found increased PS expression on several immune subsets in the blood of patients with metastatic melanoma after receiving tumor-directed RT. These findings highlight the potential of combining PS targeting with RT and PD-1 pathway blockade to improve outcomes in patients with advanced-stage cancers.

2.
Clin Cancer Res ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509808

RESUMO

PURPOSE: Cutaneous and unknown primary melanomas frequently harbor alterations that activate the Mitogen Activated Protein Kinase (MAPK) pathway. Whether MAPK driver detection beyond BRAF V600 is clinically relevant in the checkpoint inhibitor era is unknown. METHODS: Patients with melanoma were prospectivelyofferedtumor sequencingof 341-468 genes. Oncogenic alterations in 28 RTK-RAS-MAPK pathway genes were used to construct MAPK driver groups. Time to treatment failure(TTF)was determinedfor patients who received frontline PD-1 monotherapy,nivolumab plus ipilimumab,or subsequentgenomically matched targeted therapies.A Cox proportional hazards model was constructed for TTF using driver group and clinical variables. RESULTS: 670 of 696 sequenced melanomas (96%) harbored an oncogenic RTK-RAS-MAPK pathway alteration; 33% had {greater than or equal to}1 driver. Nine driver groups varied by clinical presentation and mutational burden. TTF of PD-1 monotherapy (N=181) varied by driver, with worse outcomes for NRAS Q61 and BRAF V600 versus NF1 or other alterations (median 4.2, 7.5, 22 and not reached;p<0.0001). Driver group remained significant independent of TMB and clinical features. TTF did not vary by driver for nivolumab plus ipilimumab (N=141). Among 172 patients with BRAF V600 wild-type melanoma who progressed on checkpoint blockade, 27 were treated with genomically matched therapy, and 8 (30%) derived clinical benefit lasting {greater than or equal to}6 months. CONCLUSION: Targeted capture multigene sequencingcan detect oncogenicRTK-RAS-MAPK pathway alterations in almost allcutaneous and unknown primary melanomas. Time to treatment failure of PD-1 monotherapy varies by mechanism of ERK activation.Oncogenic kinase fusionscan be successfully targetedin immune checkpointinhibitor-refractory melanoma.

5.
Head Neck ; 42(11): 3316-3325, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32737953

RESUMO

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with high mortality. Identifying patients at risk of distant metastasis assists with management and prognostication. We aimed to define the relationship between volume, survival, and risk of distant metastases. METHODS: A retrospective review of all patients with SNMM treated at a single institution over a 21-year period was conducted. Tumor volume was calculated using cross-sectional imaging and survival analysis was performed. RESULTS: Sixty-one patients were included. Tumor volume was predictive of local progression-free survival (P = .03), distant metastases-free survival (DMFS) (P = .002), and overall survival (OS) (P = .02). It was a better predictor than AJCC stage and T-classification. Tumor volume equal to or greater than 5 cm3 was associated with a significantly worse DMFS and OS (P = .02 and .009, respectively). CONCLUSION: Calculation of tumor volume assists in quantifying the risk of distant metastases and death in SNMM.

6.
J Am Acad Dermatol ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32827607

RESUMO

BACKGROUND: Radiation therapy (RT) is a treatment option for selected skin cancers. The histologic effects of RT on normal skin or skin cancers are not well-characterized. Dermoscopy, high frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are non-invasive imaging modalities that may help characterize RT response. OBJECTIVES: To describe changes in the tumor and surrounding skin of basal cell carcinoma (BCC) patients treated with RT. METHODS: The study was conducted between 2014-2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, RCM were performed before treatment, 6 weeks, 3 months and 12 months after RT. RESULTS: 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. Presence of BCC-specific features were present in 81.8%, 91% and 17% of patients imaged with dermoscopy, RCM and HFUS at baseline, prior to treatment. After treatment, resolution of these features was noted in 33.4%, 91.7%, and 100% of patients imaged with the respective modalities. No recurrences were seen after 31.7 months mean follow-up. LIMITATIONS: Small sample size and no histopathological correlation. CONCLUSION: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCCs RT response.

7.
J Natl Cancer Inst ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32726432

RESUMO

BACKGROUND: Radiation therapy is one of the most commonly used cancer therapeutics, but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure. METHODS: We analyzed 20,107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1,085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy. Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared to those harboring variants of unknown significance (VUS). All statistical tests were two-sided. RESULTS: Among 357 pan-cancer patients who received 727 courses of radiotherapy, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs VUS allele, respectively (HR: 0.51, 95% CI = 0.34-0.77, p= .001). The greatest clinical benefit was seen in tumors harboring bi-allelic ATM inactivation (HR = 0.19, 95% CI = 0.06-0.60, p=.005), with statistically significant benefit also observed in tumors with mono-allelic ATM inactivation (HR = 0.57, 95% CI = 0.35-0.92, p=.02). Notably, ATM LoF was highly predictive of outcome in TP53 wild type tumors, but not among TP53-mutant tumors. CONCLUSION: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following radiotherapy. The identification of a radiosensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically-guided radiotherapy.

8.
Ocul Oncol Pathol ; 6(3): 184-195, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32509764

RESUMO

Background: Patients with uveal melanoma (UM) are known to have quality of life (QOL) issues after treatment, but QOL concerns after initial diagnosis are ill-defined. Objectives: We studied the QOL concerns of patients with UM after initial diagnosis to identify factors associated with QOL. Method: Between September 2011 and May 2016, UM planning to undergo radiotherapy completed the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ)-C30, as well as the Ophthalmic Oncology module, QLQ-OPT30. Demographic, ophthalmic, and tumor related characteristics were recorded. The primary outcome was the QOL score and fraction of patients reporting any or severe symptoms. A multiple stepwise regression model investigated the association of demographic, ophthalmic, and tumor characteristics with QOL. Results: QOL concerns were assessed in 201 subjects. The majority (51/60) of QOL items had a high response rate (≥90%), and internal consistency on scales (median Cronbach α = 0.85) with the most common severe QOL concern being worry about disease recurrence (41%). The most common ophthalmic symptoms reported were vision impairment (81%) and ocular irritation (66%). Multivariable regression modeling demonstrated several significant associations. Conclusions: Severe worry about UM recurrence, ocular irritation, and vision impairment was reported by many patients. Clinicians should be aware of these concerns and implement management strategies.

9.
Cancer ; 126(17): 3900-3906, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478867

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.


Assuntos
Betacoronavirus , Tomada de Decisão Clínica/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Médicos/psicologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapia , Comorbidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Humanos , Hospedeiro Imunocomprometido , Morbidade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Tempo para o Tratamento
10.
J Am Acad Dermatol ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32423829

RESUMO

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

11.
Brachytherapy ; 19(4): 415-426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32409128

RESUMO

PURPOSE: Keratinocyte carcinoma (KC, previously nonmelanoma skin cancer) represents the most common cancer worldwide. While surgical treatment is commonly utilized, various radiation therapy techniques are available including external beam and brachytherapy. As such, the American Brachytherapy Society has created an updated consensus statement regarding the use of brachytherapy in the treatment of KCs. METHODS: Physicians and physicists with expertise in skin cancer and brachytherapy created a consensus statement for appropriate patient selection, data, dosimetry, and utilization of skin brachytherapy and techniques based on a literature search and clinical experience. RESULTS: Guidelines for patient selection, evaluation, and dose/fractionation schedules to optimize outcomes for patients with KC undergoing brachytherapy are presented. Studies of electronic brachytherapy are emerging, although limited long-term data or comparative data are available. Radionuclide-based brachytherapy represents an appropriate option for patients with small KCs with multiple techniques available. CONCLUSIONS: Skin brachytherapy represents a standard of care option for appropriately selected patients with KC. Radionuclide-based brachytherapy represents a well-established technique; however, the current recommendation is that electronic brachytherapy be used for KC on prospective clinical trial or registry because of a paucity of mature data.

12.
Clin Cancer Res ; 26(13): 3193-3201, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32205463

RESUMO

PURPOSE: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab. PATIENTS AND METHODS: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety. RESULTS: Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients. CONCLUSIONS: RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.

13.
J Am Soc Mass Spectrom ; 31(3): 498-507, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013416

RESUMO

Acylcarnitines have been identified in human and animal metabolomic-profiling studies as urinary markers of radiation exposure, a result which is consistent with their cytoprotective effects and roles in energy metabolism. In the present work, a rapid method for quantitation of the more abundant acylcarnitines in human urine is developed using a valuable set of samples from cancer patients who received total body irradiation (TBI) at Memorial Sloan Kettering Cancer Center. The method uses solid-phase extraction (SPE) processing followed by differential mobility spectrometry (DMS with ethyl acetate modifier) tandem mass spectrometry (ESI-DMS-MS/MS) with deuterated internal standards. The analyzed human urine samples were collected from 38 individual patients at three time points over 24 h during and after the course of radiation treatment, a design allowing each patient to act as their own control and creatinine normalization. Creatinine-normalized concentrations for nine urinary acylcarnitine (acyl-CN) species are reported. Six acyl-CN species were reduced at the 6 h point. Acetylcarnitine (C2:0-CN) and valerylcarnitine (C5:0-CN) showed recovery at 24 h, but none of the other acyl-CN species showed recovery at that point. Levels of three acyl-CN species were not significantly altered by radiation. This rapid quantitative method for clinical samples covers the short- and medium-chain acylcarnitines and has the flexibility to be expanded to cover additional radiation-linked metabolites. The human data presented here indicates the utility of the current approach as a rapid, quantitative technique with potential applications by the medical community, by space research laboratories concerned with radiation exposure, and by disaster response groups.

14.
J Am Acad Dermatol ; 82(4): 878-886, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31562942

RESUMO

BACKGROUND: There are no specific recommendations for [18F] fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in assessing recurrent cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To evaluate FDG-PET/CT in recurrent cSCC. METHODS: FDG-PET/CT scans were retrospectively reviewed. Sites of abnormal uptake were noted and correlated with biopsy/histopathology studies, where available, and with follow-up imaging or clinical data in others. Comparison with available CT/magnetic resonance imaging was performed. The prognostic significance of PET/CT parameters was evaluated, and PET/CT-based change in management was recorded. RESULTS: A total of 115 FDG-PET/CT scans were analyzed in 100 consecutive patients with cSCC. Of these, 96 (84%) scans were positive for recurrence, and 25 showed distant metastases. PET/CT detected unsuspected disease sites in 39 of 115 scans (34%), locoregional disease in 14, distant metastases in 11, both locoregional disease and distant metastases in 8, additional local cutaneous disease in 5, and second malignancy in 1. Comparison of 78 PET/CT scans with available CT/magnetic resonance imaging showed 37 additional abnormalities on 23 PET/CT scans, predominantly including skin/subcutaneous lesions and nodes. PET/CT led to change in management in 28% of patients. On univariate/multivariate analysis, increased number of FDG-positive lesions and lung metastases on PET/CT was associated with increased risk of death/disease progression. LIMITATIONS: Retrospective study. CONCLUSIONS: FDG-PET/CT was sensitive in detecting recurrent disease in cSCC, led to change in management for 28% of patients, and proved to be of prognostic value.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do Tratamento
15.
J Nucl Med ; 61(4): 512-519, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586002

RESUMO

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1-2, 6-8, 24, 48, and 96-144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time-activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24-48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C-positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell-rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.


Assuntos
Antígenos CD8/imunologia , Imunoconjugados/química , Imunoconjugados/farmacocinética , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Radioisótopos , Zircônio , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Feminino , Humanos , Imunoconjugados/sangue , Imunoconjugados/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Distribuição Tecidual
16.
Pract Radiat Oncol ; 10(1): 8-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31831330

RESUMO

PURPOSE: This guideline reviews the evidence for the use of definitive and postoperative radiation therapy (RT) in patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on indications for RT in the definitive and postoperative setting for BCC and cSCC, as well as dose-fractionation schemes, target volumes, basic aspects of treatment planning, choice of radiation modality, and the role of systemic therapy in combination with radiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The guideline recommends definitive RT as primary treatment for patients with BCC and cSCC who are not surgical candidates while conditionally recommending RT with an emphasis on shared decision-making in those situations in which adequate resection can lead to a less than satisfactory cosmetic or functional outcome. In the postoperative setting, a number of indications for RT after an adequate resection are provided while distinguishing the strength of the recommendations between BCC and cSCC. One key question is dedicated to defining indications for regional nodal irradiation. The task force suggests a range of appropriate dose-fractionation schemes for treatment of primary and nodal volumes in definitive and postoperative scenarios. The guideline also recommends against the use of carboplatin concurrently with adjuvant RT and conditionally recommends the use of systemic therapies for unresectable primaries where treatment may need escalation. CONCLUSIONS: Defining the role of RT in the management of BCC and cSCC has been hindered by a lack of high-quality evidence. This document synthesizes available evidence to define practice guidelines for the most common clinical situations. We encourage practitioners to enroll patients in prospective trials and to approach care in a multidisciplinary fashion whenever possible.


Assuntos
Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Medicina Baseada em Evidências/normas , Radioterapia (Especialidade)/normas , Neoplasias Cutâneas/terapia , Fracionamento da Dose de Radiação , Medicina Baseada em Evidências/métodos , Humanos , Seleção de Pacientes , Radioterapia (Especialidade)/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/normas , Sociedades Médicas/normas , Estados Unidos
17.
Cancer ; 126(4): 850-860, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31747077

RESUMO

BACKGROUND: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Radioterapia/métodos , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estudos de Coortes , Dermatite/etiologia , Fadiga/etiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfopenia/etiologia , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Radioterapia/efeitos adversos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
18.
Ophthalmology ; 127(2): 240-248, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31708274

RESUMO

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 µg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/secundário , Imunoterapia/métodos , Melanoma/patologia , Melfalan/uso terapêutico , Neoplasias Cutâneas/patologia , Corpo Vítreo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
19.
Lancet Oncol ; 20(12): e699-e714, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31797796

RESUMO

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.


Assuntos
Adenocarcinoma Sebáceo/terapia , Medicina Baseada em Evidências/normas , Guias de Prática Clínica como Assunto/normas , Neoplasias das Glândulas Sebáceas/terapia , Humanos , Prognóstico
20.
JAMA Dermatol ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31268498

RESUMO

Importance: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients. Objective: To develop recommendations for the care of adults with MAC. Evidence Review: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins. Findings: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management. Conclusions and Relevance: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA