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Radiation therapy remains a fundamental treatment for patients with cancer. Despite an increasing number of targeted molecular therapies that are US Food and Drug Administration (FDA)-approved for the treatment of patients with metastatic disease, there has been very little progress made in terms of drugs used concurrently with radiation. This article reviews the existing regulatory framework in which cancer drugs may be developed for use in combination with radiation therapy from the perspective of the FDA. To briefly summarize: (1) nonclinical studies are a critical first step to ensure that drugs are safe for use in humans; however, additional nonclinical studies of a drug with radiation may not be required before a clinical trial in combination with radiation as long as the safety profile of the drug has been characterized in humans. The FDA determines the quality of evidence required before studying a drug in combination with radiation on a case-by-case basis. (2) Although often impractical to consider late toxicities during dose-escalation, late adverse events should be captured and taken into consideration when determining the final dose and schedule to take forward during drug development. (3) There are a number of expedited programs for cancer drug development, including accelerated approval, a conditional approval that allows for use of earlier clinical endpoints when the data suggests a clinically meaningful improvement over available therapy. (4) The Agency encourages sponsors to discuss their development plan with the appropriate FDA review division in formal regulatory meetings.
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Neoplasias , Aprovação de Drogas , Combinação de Medicamentos , Humanos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Estados Unidos , United States Food and Drug AdministrationRESUMO
Cervical cancer is a socially and scientifically distinguishable disease. Its pathogenesis, sexual transmission of high-risk HPV to a metaplastic portion of the uterine cervix, makes cervical cancer preventable by safe and effective HPV vaccines commercially available since 2006. Despite this, cervical cancer remains the deadliest gynecologic cancer in the world. Regrettably, global incidence and mortality rates disproportionately affect populations where women are marginalized, where HIV infection is endemic, and where access to preventive vaccination and screening for preinvasive disease are limited. In the United States, cervical cancer incidence has gradually declined over the last 25 years, but mortality rates remain both constant and disparately higher among communities of color because of the adverse roles that racism and poverty play in outcome. Until these conditions improve and widespread prevention is possible, treatment innovations are warranted. The last standard-of-care treatment changes occurred in 1999 for locally advanced disease and in 2014 for metastatic and recurrent disease. The viral and immunologic nature of HPV-induced cervical cancer creates opportunities for both radiation and immunotherapy to improve outcomes. With the advent of T cell-directed therapy, immune checkpoint inhibition, and techniques to increase the therapeutic window of radiation treatment, an overdue wave of innovation is currently emerging in cervical cancer treatment. The purpose of this review is to describe the contemporary developmental therapeutic landscape for cervical cancer that applies to most tumors and to discuss notable rare histologic subtypes that will not be adequately addressed with these treatment innovations.
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Infecções por HIV , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Imunoterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/terapia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapiaRESUMO
oronavirus (COVID-19) has caused marked impact on graduate medical education for all medical specialties. Radiation Oncology and the American Board of Radiology have also had to rapidly adapt to converting education and examinations to virtual platforms. We describe our small pilot experience in transitioning our in-person mock oral examinations to a virtual platform. Survey-based assessment revealed excellent feedback regarding ease of use and educational usefulness. Our mock oral examinations pilot experience adds to evidence that virtual mock oral examinations are an important considerationfor Radiation Oncology education and a feasible alternative to an in-person oral examination.
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PURPOSE: When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion. METHODS AND MATERIALS: This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades. A literature review was performed to determine the publication outcomes of PRO data, including only trials that used PROs in their design and were mature enough to have published results. RESULTS: Fifty-seven (56.4%) of the 101 trials included in this study included PROs in their design. Brain and head and neck trials demonstrated the largest proportional incorporation of PROs (81.8% and 76.9%, respectively), and thoracic and breast trials used the fewest (18.8% and 37.5%, respectively). The EQ-5D family of questionnaires was the most commonly used PROs, used in 22.8% of trials included. The literature review demonstrated a pattern of increased publication of PRO data alongside survival endpoints in manuscripts derived from these trials over time. CONCLUSIONS: Though there is room for improvement, the field of radiation oncology has embraced the incorporation of PROs into multicenter, high-impact clinical trials over the past 2 decades and has increased its publication of this data alongside survival data from these trials.
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Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Neoplasias/radioterapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Estudos Transversais , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Editoração/estatística & dados numéricos , Radioterapia/efeitos adversos , Terminologia como Assunto , Fatores de TempoRESUMO
Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug-radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug-radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer.
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Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Animais , Quimiorradioterapia , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Progressão da Doença , Humanos , Projetos de Pesquisa , Resultado do TratamentoRESUMO
On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified HR of 0.66 [95% confidence interval (CI), 0.49-0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%-95.4%) in patients treated with neratinib versus 91.9% (95% CI, 90.2%-93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Clin Cancer Res; 24(15); 3486-91. ©2018 AACRSee related commentary by Unni et al., p. 3483.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Quinolinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Quinolinas/efeitos adversos , Receptor ErbB-2/genética , Trastuzumab/administração & dosagemRESUMO
A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the Radiation Research Program and Radiation Oncology Branch of the Center for Cancer Research (CCR) of the National Cancer Institute (NCI), to identify critical research areas and directions that will advance the understanding of radiation-induced fibrosis (RIF) and accelerate the development of strategies to mitigate or treat it. Experts in radiation biology, radiation oncology and related fields met to identify and prioritize the key areas for future research and clinical translation. The consensus was that several known and newly identified targets can prevent or mitigate RIF in pre-clinical models. Further, basic and translational research and focused clinical trials are needed to identify optimal agents and strategies for therapeutic use. It was felt that optimally designed preclinical models are needed to better study biomarkers that predict for development of RIF, as well as to understand when effective therapies need to be initiated in relationship to manifestation of injury. Integrating appropriate endpoints and defining efficacy in clinical trials testing treatment of RIF were felt to be critical to demonstrating efficacy. The objective of this meeting report is to (a) highlight the significance of RIF in a global context, (b) summarize recent advances in our understanding of mechanisms of RIF,
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Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/terapia , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/terapia , Radioterapia/efeitos adversos , Medicina Baseada em Evidências , Humanos , National Cancer Institute (U.S.) , Fibrose Pulmonar/etiologia , Pneumonite por Radiação/etiologia , Resultado do Tratamento , Estados UnidosRESUMO
On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36-0.59; P < 0.0001]. Safety data confirmed the known adverse reaction profile of palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968-72. ©2016 AACR.
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Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Aprovação de Drogas , Estradiol/análogos & derivados , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Estradiol/efeitos adversos , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piridinas/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
INTRODUCTION: The treatment of pediatric intracranial low-grade gliomas (LGG) generally begins with maximal safe resection. Radiation therapy (RT) and chemotherapy are typically reserved for patients with incomplete resection and/or disease progression. We report long-term treatment outcomes and toxicities in a cohort of pediatric patients with LGG after RT. METHODS: Thirty-four patients <21 years old with intracranial LGG who were treated with RT at the Johns Hopkins Hospital were included in this retrospective analysis. Patients were evaluated for overall survival (OS), progression-free survival (PFS), recurrence patterns, and treatment toxicities using descriptive statistics, Kaplan-Meier curves, and Cox proportional hazard regressions. RESULTS: The mean age at diagnosis was 7.9 years (range 1.2-18.3 years) and mean age at RT was 9.8 years (range 3.0-28.9 years). The median follow-up time was 9.8 years after radiation (range 0.8-33.3 years). The estimated 10-year OS and PFS after RT were 92 and 74 %, respectively. Twelve patients had disease progression after RT, and all recurrences were local. Two patients died due to disease progression 2.3 and 9.1 years after RT. One patient had malignant transformation of LGG to high-grade glioma. No significant predictors of PFS were identified on uni- or multivariate analysis. Late effects of LGG and treatment seen were endocrine deficiencies in 16 patients, visual problems in 10 patients, hearing loss in 4 patients, special education requirements for 5 patients, and a vascular injury/demyelination secondary to RT in 1 patient. CONCLUSION: Our study suggests that the use of radiation in patients with intracranial LGG results in excellent OS and PFS with acceptable toxicity at long-term follow-up.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Gerenciamento Clínico , Glioma/diagnóstico , Glioma/radioterapia , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
PURPOSE: The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice. METHODS AND MATERIALS: During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported. RESULTS: Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent of residents reported inadequate exposure to high-dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years. CONCLUSIONS: This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders.
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Escolha da Profissão , Internato e Residência/estatística & dados numéricos , Neoplasias/radioterapia , Radioterapia (Especialidade)/estatística & dados numéricos , Inquéritos e Questionários , Pesquisa Biomédica/educação , Pesquisa Biomédica/estatística & dados numéricos , Braquiterapia/estatística & dados numéricos , Humanos , Internato e Residência/normas , Prática Privada/estatística & dados numéricos , Radioterapia (Especialidade)/educação , Radioterapia (Especialidade)/normas , Radiocirurgia/educação , Radiocirurgia/estatística & dados numéricos , Sociedades Médicas/estatística & dados numéricos , Estados UnidosRESUMO
PURPOSE: A limitation of [(18)F] 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDGPET) in radiation planning for Hodgkin lymphoma (HL) is significant variability in delineation of tumor volume. One approach to reduce variability is to apply automatic or semiautomatic segmentation methods such as thresholding based on a percent tumor maximum standardized uptake value (SUVmax). Here, we apply various tumor SUVmax thresholds and examine their effects in involved field radiation therapy (IFRT) and involved site radiation therapy (ISRT) target volumes. METHODS AND MATERIALS: PET/computed tomography data sets were reviewed for 16 pediatric and young adult patients treated with IFRT. The following percent tumor SUVmax thresholds were applied to the prechemotherapy PET: 15%, 20%, 25%, 30%, 35%, and 40%. Clinical target volumes for IFRT and ISRT plans were manually generated based on these threshold volumes (CTVPET) and compared with clinical target volumes generated using the standard qualitative visual method (CTVQVM). Treatment plans were generated, doses to normal structures were compared, and the optimum threshold, defined as the CTVPET that corresponded to the percent overlap closest to 100% when compared with the CTVQVM, was determined. RESULTS: On average, there was a 7.6-fold increase in PET volume between 40% and 15% SUVmax. When the 6 SUVmax thresholds were applied in the design of target volumes for IFRT, 2 of 16 patients had a change in treatment volume. There was a 2.4-fold increase in ISRT CTVs generated based on the 15% and 40% SUVmax, which translated into a clinically significant decrease in dose to normal structures when the ISRT plans that were generated using the 15% SUVmax volumes were compared with the 40% SUVmax. In most patients, the optimum threshold was SUVmax 15%. CONCLUSIONS: Accurate target volume delineation with [(18)F] 2-fluoro-2-deoxy-d-glucose PET in HL is challenging and may require more precise and reproducible segmentation methods as we move toward more conformal therapies.
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Fluordesoxiglucose F18/farmacocinética , Doença de Hodgkin/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Planejamento da Radioterapia Assistida por Computador/métodos , Adolescente , Adulto , Criança , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto JovemAssuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Endossonografia , Marcadores Fiduciais , Neoplasias Retais/radioterapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL. PATIENTS AND METHODS: Data from 77 patients were evaluated. At initial presentation, disease and performance status were assessed, as well as QoL, which was obtained with the European Organisation for Research and Treatment of Cancer QLQ-PAN26 questionnaire. Statistical analyses examined associations between QoL, disease status, and performance status. RESULTS: Digestive symptoms (P < .003) significantly differed by pancreatic disease status (resectable, resected, locally advanced, and metastatic). Patients with a worse performance status, defined as Eastern Cooperative Oncology Group ≥ 1, were more likely to report symptomatic pancreatic pain (P = .001), digestive symptoms (P = .017), cachexia (P = .004), and ascites (P < .001) compared with patients with a performance status of 0. The majority (92%) of patients reported a significant fear of future health problems, regardless of disease status or performance status. CONCLUSION: Although several measures of QoL have been observed in all patients, certain measures appear to correlate specifically with worse disease status. Therefore, routine assessment of QoL is suggested in order to guide treatment decisions. Further investigation on optimizing the use of QoL measures and patient-reported outcomes to better tailor management is warranted.
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Neoplasias Pancreáticas/patologia , Qualidade de Vida , Índice de Gravidade de Doença , Idoso , Institutos de Câncer , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/epidemiologia , AutorrelatoRESUMO
Knowledge of the basic mechanisms of the immune system as it relates to cancer has been increasing rapidly. These developments have accelerated the translation of these advancements into medical breakthroughs for many cancer patients. The immune system is designed to discriminate between self and non-self, and through genetic recombination there is virtually no limit to the number of antigens it can recognize. Thus, mutational events, translocations, and other genetic abnormalities within cancer cells may be distinguished as "altered-self" and these differences may play an important role in preventing the development or progression of cancer. However, tumors may utilize a variety of mechanisms to evade the immune system as well. Cancer biologists are aiming to both better understand the relationship between tumors and the normal immune system, and to look for ways to alter the playing field for cancer immunotherapy. Summarized in this review are discussions from the 2013 SITC Primer, which focused on reviewing current knowledge and future directions of research related to tumor immunology and cancer immunotherapy, including sessions on innate immunity, adaptive immunity, therapeutic approaches (dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, and immune checkpoint blockade), challenges to driving an anti-tumor immune response, monitoring immune responses, and the future of immunotherapy clinical trial design.
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A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy. Similarly, when disease progression is mistaken for treatment effect, a potentially ineffective therapy may be continued in the face of progressive disease. Here we describe the three types of radiation injury to the brain based on the time to development of signs and symptoms--acute, subacute and late--and then review specific imaging changes after intensity-modulated radiation therapy, stereotactic radiosurgery and brachytherapy. We provide an overview of these phenomena in the treatment of a wide range of malignant and benign CNS illnesses. Finally, we review the published data regarding imaging techniques under investigation to address this well-known problem.
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Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Encéfalo/efeitos da radiação , Diagnóstico por Imagem/métodos , Lesões por Radiação/diagnóstico , Animais , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Progressão da Doença , Humanos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Involved field radiation therapy (IFRT) is integral in curative therapy for Hodgkin lymphoma (HL), although primarily used in patients with intermediate/high-risk HL. We present failure patterns and clinical outcomes in a cohort of pediatric and young adult patients with HL treated with IFRT at the Johns Hopkins Hospital. PROCEDURE: Patients ≤40 years old with intermediate/high-risk HL who received chemotherapy and IFRT from 1997 to 2012 were included in this retrospective analysis. Patients were evaluated for failure patterns, overall survival (OS), and event-free survival (EFS) using Kaplan-Meier curves, descriptive statistics, and Cox proportional hazard regressions. RESULTS: We reviewed 74 patients (45 pediatric and 29 young adult) with a median follow-up of 4.4 years. The mean age at diagnosis was 21.4 years. Patients received a median of 29.75 Gy of IFRT (range 15-39.6 Gy). The majority of pediatric patients received ABVE-PC chemotherapy (n = 25) and <30 Gy of radiation (n = 33) while most young adults received ABVD chemotherapy (n = 24) and ≥30 Gy (n = 25). Estimated 5-year OS and EFS were 96% and 81%, respectively. Thirteen patients had recurrence; eight were pediatric. Distant relapse alone comprised 83% of failures in patients receiving ≥30 Gy. Of the seven patients who received <30 Gy and had recurrence, six had local failure as a component of their recurrence. Caucasian race (P = 0.02) and nodular sclerosing histology (P = 0.01) predicted for increased EFS. Late effects were minimal and all deaths (n = 4) were from HL. CONCLUSIONS: In this series, pediatric and young adult patients were treated with differing chemoradiation and had distinct recurrence patterns.
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Quimiorradioterapia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/diagnóstico , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
We present an unusual case of a germinoma of the pineal region arising adjacent to an epidermoid cyst in a 16-year-old male. Initial imaging findings were classic for epidermoid cyst. The patient underwent two partial resections at an outside institution, each specimen demonstrating pure epidermoid cyst. Follow-up imaging over a period of 24 months showed an area of progressive contrast enhancement adjacent to the initial lesion, suggesting the development of a neoplasm. Given the area of contrast enhancement in addition to worsening headaches and visual changes, he underwent a third and final resection at our institution. Pathology revealed a mixed germ cell tumor with prominent germinoma component in addition to a well-differentiated epidermoid cyst. Details of his imaging and pathologic findings are presented, and possible explanations for these findings are explored, the most likely of which is lack of complete resection at the onset failed to identify the whole of the neoplasm. We conclude that pediatric epidermoid cysts of the pineal region should always receive close follow-up, particularly when total resection is not performed.