ABSTRACT BACKGROUND: Radiation therapy (RT) is a standard treatment for non-metastatic breast cancer and is associated with acute and late toxicities. Intensity-modulated RT (IMRT) may decrease toxicity and is convenient for patients. OBJECTIVES: To assess the efficacy and safety of IMRT in women with early stage breast cancer. DESIGN AND SETTING: Systematic review study; Multi-institutional centers. METHODS: Seven databases were searched. Randomized controlled trials (RCT) comparing IMRT with any “non-IMRT” strategies were included. Primary outcomes were local control and acute toxicity. Cochrane Handbook was use to plan and conduct the review, and PRISMA 2020 was used to report results. RESULTS: Five RCT involving 2,556 women (n = 1,283 IMRT; n = 1,274 control arm) were included. Baseline characteristics were similar between trials and arms. Local relapse-free survival rates were not different (hazard-ratio [HR] 0.62; 95%confidence interval [CI] -0.38 to 1.62; P > 0.05); however, IMRT reduced the overall acute toxicity (RR 0.69, 95%CI 0.58 to 0.82; P < 0.00001) and acute moist desquamation (risk-ratio [RR] 0.71, 95%CI 0.60 to 0.82; P < 0.00001). Lymphedema and pneumonitis rates, and survival outcomes were not affected by IMRT. The 2-year telangiectasia rate was decreased with IMRT (RR 0.66, 95%CI 0.47 to 0.93; P = 0.02); however, edema, pain, pigmentation, or fibrosis remained unaffected. IMRT did not improve cosmesis. CONCLUSIONS: IMRT improved acute toxicity and lowered telangiectasia rates, without affecting oncological and aesthetic outcomes. SYSTEMATIC REVIEW REGISTRATION: This review was registered at Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010420. https://doi.org/10.1002/14651858.CD010420. BACKGROUND (RT nonmetastatic non metastatic toxicities Intensitymodulated Intensity modulated (IMRT patients OBJECTIVES SETTING study Multiinstitutional Multi institutional centers METHODS searched (RCT nonIMRT “non-IMRT included 202 results RESULTS 2556 2 556 2,55 1283 1 283 1,28 1274 274 1,27 arm arms relapsefree relapse free hazardratio hazard ratio HR [HR 0.62 062 0 62 95confidence confidence 95 CI [CI 0.38 038 38 -0.3 1.62 162 0.05 005 05 0.05) however RR 069 69 0.69 95CI 058 58 0.5 0.82 082 82 0.00001 000001 00001 riskratio risk [RR 071 71 0.71 060 60 0.6 0.00001. . 2year year 066 66 0.66 047 47 0.4 0.93 093 93 0.02 002 02 0.02) edema pain pigmentation unaffected cosmesis CONCLUSIONS REGISTRATION 2013 3 Art No. No CD010420 CD https//doi.org/10.1002/14651858.CD010420. httpsdoiorg10100214651858CD010420 httpsdoiorgCD https //doi.org/10.1002/14651858.CD010420. doi org 10 1002 14651858 https://doi.org/10.1002/14651858.CD010420 20 255 55 2,5 128 28 1,2 127 27 06 6 9 0.3 03 -0. 1.6 16 0.0 00 5 0. 0.8 08 8 0.0000 00000 0000 07 7 0.7 04 4 0.9 09 201 CD01042 https//doi.org/10.1002/14651858.CD010420 httpsdoiorg httpsdoiorg10100214651858CD01042 doiorg10100214651858CD010420 doiorgCD //doi.org/10.1002/14651858.CD010420 100 1465185 https://doi.org/10.1002/14651858.CD01042 25 2, 12 1, -0 1. 0.000 000 CD0104 https//doi.org/10.1002/14651858.CD01042 httpsdoiorg10100214651858CD0104 doiorg doiorg10100214651858CD01042 //doi.org/10.1002/14651858.CD01042 146518 https://doi.org/10.1002/14651858.CD0104 - 0.00 CD010 https//doi.org/10.1002/14651858.CD0104 httpsdoiorg10100214651858CD010 doiorg10100214651858CD0104 //doi.org/10.1002/14651858.CD0104 14651 https://doi.org/10.1002/14651858.CD010 CD01 https//doi.org/10.1002/14651858.CD010 httpsdoiorg10100214651858CD01 doiorg10100214651858CD010 //doi.org/10.1002/14651858.CD010 1465 https://doi.org/10.1002/14651858.CD01 CD0 https//doi.org/10.1002/14651858.CD01 httpsdoiorg10100214651858CD0 doiorg10100214651858CD01 //doi.org/10.1002/14651858.CD01 146 https://doi.org/10.1002/14651858.CD0 https//doi.org/10.1002/14651858.CD0 httpsdoiorg10100214651858CD doiorg10100214651858CD0 //doi.org/10.1002/14651858.CD0 14 https://doi.org/10.1002/14651858.CD https//doi.org/10.1002/14651858.CD doiorg10100214651858CD //doi.org/10.1002/14651858.CD

RESUMO INTRODUÇÃO: A radioterapia é amplamente utilizada como tratamento adjuvante nas pacientes com câncer de mama. Nas últimas décadas, diversos estudos foram desenhados para avaliar a segurança e a eficácia da radioterapia hipofracionada moderada de mama. Mais recentemente, esquemas ainda mais curtos, com doses acima de 4 Gy (hiper-hipofracionamento), foram também propostos. Este estudo tem o objetivo de apresentar uma revisão narrativa dos diversos protocolos de hipofracionamento utilizados no tratamento do câncer de mama com o foco na aplicação clínica. RESULTADOS: Os resultados de longo prazo de diversos ensaios clínicos randomizados fase III demonstraram a segurança e a eficácia da radioterapia hipofracionada moderada utilizando 15 ou 16 frações para doença inicial e localmente avançada. Os resultados dos ensaios clínicos iniciais de hiper-hipofracionamento são também animadores e acredita-se que esses esquemas poderão se tornar rotina na indicação do tratamento adjuvante com radioterapia após a maturação dos estudos em andamento sobre esse tema. CONCLUSÕES: A ideia de que os tecidos normais poderiam apresentar toxicidade elevada com doses acima de 2 Gy foi pioneiramente contraposta por ensaios clínicos que comprovaram que o hipofracionado moderado apresentava resultados semelhantes em relação aos desfechos oncológicos e cosméticos quando comparados ao fracionamento convencional. Os resultados cosméticos e de toxicidade dos estudos de hiper-hipofracionamento são, em princípio, favoráveis. Todavia, ainda se aguardam os resultados oncológicos de longo prazo dos estudos que aplicaram o hiper-hipofracionamento para o tratamento das pacientes com câncer de mama.

SUMMARY INTRODUCTION: Radiation therapy is widely used as adjuvant treatment in breast cancer patients. In the last decades, several studies have been designed to evaluate the safety and efficacy of hypofractionated breast radiation therapy. More recently, even shorter regimens with doses above 4 Gy (hyper-hypofractionation) have also been proposed. This study aims to present a narrative review of the various hypofractionation protocols used to treat breast cancer patients with a focus on clinical application. RESULTS: Long-term results from several phase III randomized controlled trials demonstrated the safety and efficacy of hypofractionated breast radiation therapy using 15 or 16 fractions for early and locally advanced disease. The results of the initial clinical trials of hyper-hypofractionation are also encouraging and it is believed that these regimens may become routine in the indication of adjuvant radiation therapy treatment after the ongoing studies on this subject have matured. CONCLUSIONS: The idea that normal tissues could present high toxicity at doses above 2 Gy was opposed by clinical trials that demonstrated that moderate hypofractionation had similar results regarding oncological and cosmetic outcomes compared to conventional fractionation. Cosmetic and toxicity results from hyper-fractionation studies are in principle favorable. However, the long-term oncological results of studies that used hyper-hypofractionation for the treatment of breast cancer patients are still awaited.

Abstract Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

RESUMO INTRODUÇÃO A radioterapia (RT) tem importante papel no tratamento dos pacientes com neoplasia de cabeça e pescoço, sendo frequentemente utilizada como terapia adjuvante a fim de diminuir a probabilidade de recorrência local. O presente estudo tem o objetivo de realizar uma revisão da literatura para avaliar os fatores terapêuticos temporais que possam ter influência sobre os desfechos clínicos dos pacientes com neoplasia avançada de cabeça e pescoço tratados com RT adjuvante. RESULTADOS As variáveis terapêuticas, como o tempo total do tratamento, a duração da RT e a ausência de interrupções durante o tratamento radioterápico são capazes de impactar o resultado clínico dos pacientes. CONCLUSÕES Da mesma forma que determinados fatores tumorais podem afetar o prognóstico de pacientes com carcinoma de células escamosas de cabeça e pescoço, alguns fatores terapêuticos temporais também constituem fatores prognósticos e, portanto, devem ser rigorosamente orquestrados a fim de se evitarem prejuízos sobrepostos para esses pacientes.

SUMMARY INTRODUCTION Radiotherapy (RT) plays an important role in the treatment of patients with head and neck neoplasia, and is frequently used as postoperative adjuvant therapy. This study aimed to review the literature about timing factors that may influence the clinical outcomes of patients with advanced head and neck neoplasia treated with adjuvant RT. RESULTS Timing factors such as total treatment time, length of adjuvant RT, and the absence of interruptions during RT may influence the clinical outcome of these patients. CONCLUSIONS In the same way that certain tumor factors can affect the prognosis of patients with squamous cell carcinoma of the head and neck, some therapeutic timing factors are also prognostic factors and therefore, must be carefully orchestrated in order to avoid loss at therapeutic outcomes for these patients.

OBJECTIVE: This study aimed to evaluate the effect of the delay to initiate postoperative radiation therapy (RT) on locoregional control to head and neck squamous cell carcinoma patients. METHODS: Retrospective cohort study that included patients submitted to surgery followed by adjuvant RT (with/without chemotherapy). The time interval between surgery and RT was dichotomized by the receiver operating characteristics curve method at 92 days. Other possible sources of heterogeneity with potential impact on locoregional control were explored by regressive analysis. RESULTS: A total of 168 patients were evaluated. The median time for locoregional recurrence (LRR) was 29.7 months. The relapse-free survival rates were 66.4% and 75.4% for patients who initiated RT more than and within 92 postoperative days (p=0.377), respectively. Doses lower than 60Gy were associated with worse rates of locoregional control (HR=6.523; 95%CI:2.266-18.777, p=0.001). Patients whose total treatment time (TTT) was longer than 150 days had LRR rate of 41.8%; no patient with TTT inferior to 150 days had relapses (p=0.001). CONCLUSIONS: The interval between surgery and RT did not show influence on locoregional control rates. However, doses <60Gy and the total treatment time >150 days were associated with lower locoregional control rates.

ABSTRACT Objectives: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. Materials and Methods: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. Results: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. Conclusions: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO OBJETIVO: Avaliar a satisfação cosmética de pacientes diagnosticadas com câncer de mama submetidas à radioterapia hipofracionada com técnica IMRT (hIMRT) e sua correlação com dados dosimétricos do planejamento radioterápico. MATERIAIS E MÉTODOS: Estudo de coorte retrospectivo que avaliou mulheres com diagnóstico de neoplasia maligna de mama submetidas a tratamento conservador ou mastectomia radical e tratadas com hIMRT. No período de agosto de 2007 a dezembro de 2014, em uma instituição filantrópica/particular, foram selecionados 170 prontuários. A avaliação cosmética foi feita por meio da escala de Harvard/RTOG/NSABP com um intervalo mínimo de um ano após o tratamento. Dados dosimétricos coletados foram: volume da mama/plastrão, volume que recebeu 95% (V95%) e 107% (V107%) da dose prescrita. RESULTADOS: O volume das mamas tratadas variou de 169 a 2.103 ml (mediana = 702; IQR: 535 a 914 ml). O V95% mediano foi 86,7% (54,6-96,6%; IQR: 80,0% a 90,6%); oito (5,7%) pacientes tiveram o V95% superior a 95%. O V107% mediano foi 0% (0%-16,3%; IQR: 0,0% a 0,3% e 13); 9,3% pacientes tiveram o V107% superior a 2%. Cento e trinta e três (78,2%) pacientes responderam à avaliação cosmética: 99 (74,4%) consideraram o resultado cosmético excelente. Não foram encontradas associações significativas entre a avaliação cosmética e o volume da mama (p=0,875), V95% (p=0,294) e V107% (p=0,301). CONCLUSÕES: Os resultados cosméticos mostraram-se favoráveis com o uso de hIMRT, e a ausência de correlação com os dados dosimétricos usuais ilustra a capacidade do hIMRT em minimizar a heterogeneidade da dose neste desfecho, mesmo em mamas volumosas.

SUMMARY OBJECTIVE: To assess the cosmetic satisfaction of patients diagnosed with breast cancer submitted to the hypofractionated radiotherapy with IMRT (hIMRT) technique and its correlation with dosimetric data of the radiotherapy planning. MATERIALS AND METHODS: The retrospective cohort study that assessed women with a diagnosis of malignant breast neoplasia submitted to the conservative treatment or radical mastectomy and treated with hIMRT. In the period between August 2007 to December 2014, in a philanthropic / private institution, 170 records were selected. The cosmetic assessment was carried out by means of the Harvard/RTOG/NSABP scale with one-year minimum range after treatment. The collected dosimetric data were: breast / chest wall volume, volume that received 95% (V95%) and 107% (V107%) of the prescribed dose. RESULTS: The volume of the treated breasts ranged from 169 to 2.103 ml (median = 702; IQR: 535 to 914 ml). Median V95% was 86.7% (54.6-96.6%; IQR: 80.0% to 90.6%); eight (5.7%) patients had V95% higher than 95%. Median V107% was 0% (0%-16.3%; IQR: 0.0% to 0.3% and 13); 9.3% patients had V107% higher than 2%. One hundred and thirty-three (78.2%) patients responded to the cosmetic assessment: 99 (74.4%) considered the cosmetic results excellent. Significant associations between cosmetic assessment and breast volume (p=0.875), V95% (p=0.294) e V107% (p=0.301) were not found. CONCLUSION: The cosmetic results showed favorable when using hIMRT, and the lack of correlation with usual the dosimetric data illustrates the capacity of hIMRT to minimize the heterogeneity of the dose in this endpoint, even in voluminous breasts.

RESUMO Este consenso de recomendações para a radioterapia (RT) hipofracionada de toda a mama foi organizado pela Sociedade Brasileira de Radioterapia (SBRT) considerando o cenário ideal para indicação e segurança na tecnologia aplicada. Questões de controvérsias e contraindicações (RT hipofracionada em pacientes submetidas à quimioterapia [QT], RT hipofracionada nas drenagens linfáticas, RT hipofracionada após mastectomia com ou sem reconstrução imediata, a realização de reforço de dose em leito cirúrgico [ou boost], RT hipofracionada em pacientes com idade menor que 50 anos, RT hipofracionada em mamas volumosas, RT hipofracionada em histologia de carcinoma in situ [CDIS]) foram discutidas em encontro presencial, sendo o consenso atingido quando existisse concordância de pelo menos 75% dos panelistas. O grau de recomendação foi também sugerido de acordo com o nível de evidência científico disponível, qualificado entre fraco, médio ou forte. Assim, este consenso deverá servir para auxiliar os especialistas da radioterapia brasileira em relação às indicações e particularidades dessa técnica, como uma alternativa segura e viável para a realidade nacional.

SUMMARY This recommendation consensus for hypofractionated whole-breast radiotherapy (RT) was organized by the Brazilian Society of Radiotherapy (SBRT) considering the optimal scenario for indication and safety in the technology applied. All controversies and contraindication matters (hypofractionated RT in patients who underwent chemotherapy [CT], hypofractionated RT in lymphatic drainage, hypofractionated RT after mastectomy with or without immediate reconstruction, boost during surgery, hypofractionated RT in patients under 50 years old, hypofractionated RT in large breasts, hypofractionated RT in histology of carcinoma in situ [DCIS]) was discussed during a meeting in person, and a consensus was reached when there was an agreement of at least 75% among panel members. The grade for recommendation was also suggested according to the level of scientific evidence available, qualified as weak, medium, or strong. Thus, this consensus will aid Brazilian radiotherapy experts regarding indications and particularities of this technique as a viable and safe alternative for the national reality.

RESUMO INTRODUÇÃO: Foi realizada uma análise de custo-efetividade da radioterapia com intensidade modulada de feixe (IMRT) comparada com a radioterapia conformada para pacientes com câncer de cabeça e pescoço (CCP) no contexto do Sistema Único de Saúde (SUS). MÉTODOS: Foi elaborado um modelo de Markov para comparar os custos médicos diretos e os desfechos de saúde relacionados à qualidade de vida do paciente pós-intervenção radioterápica sofrendo de xerostomia e disfagia. Com essa finalidade, foram usados os dados do estudo PARSPORT e parâmetros de qualidade de vida. Os resultados comparativos das estratégias alternativas de tratamento foram medidos pela razão de custo-efetividade incremental (RCEI). O desfecho analisado foi o de anos de vida ajustados à qualidade (QALY). RESULTADOS: Em um horizonte de tempo de dois anos, a IMRT foi associada com um benefício incremental de ganho de 0,16 QALYs por indivíduo, resultando em um RCEI de R$ 31.579 por QALY ganhado. A IMRT foi custo-efetivo, adotando-se o limite máximo de disposição a pagar, proposto pela OMS, de três vezes o PIB per capita nacional, equivalente a R$ 72.195. No horizonte de tempo de 15 anos, o benefício incremental de ganho foi de 1,16 QALYs por indivíduo, com um RCEI de R$ 4.341. A IMRT foi custo-efetivo, adotando-se o limite de disposição a pagar, proposto pela OMS, de uma vez o PIB per capita nacional, equivalente a R$ 24.065. CONCLUSÃO: A IMRT foi considerada um tratamento custo-efetivo na perspectiva do SUS.

SUMMARY BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

CONTEXTO E OBJETIVO: Até onde sabemos, não há avaliação sistemática da classificação da produção científica no âmbito da radioterapia de tumores de sistema nervoso central. O objetivo deste estudo foi avaliar sistematicamente o estado das evidências relativas ao sistema nervoso central e avaliar origem geográfica e a temática envolvida nestas publicações.TIPO DE ESTUDO E LOCAL: Estudo descritivo de avaliação crítica, realizado em um hospital privado em São Paulo, Brasil.MÉTODOS: Foram avaliados todos os estudos publicados em sistema nervoso central na revista Radiotherapy & Oncology, entre 2003 e 2012. Os estudos identificados foram classificados de acordo com o desenho metodológico e nível de evidência. Informações sobre a localização geográfica do estudo, instituições e os autores envolvidos nas publicações, a principal condição ou doença estudada e o período de publicação também foram obtidos.RESULTADOS: Foram identificados 3.004 estudos publicados no período de 10 anos. Destes, 125 (4,2%) foram considerados como elegíveis, e 66% destes eram séries de casos. As revisões sistemáticas e ensaios clínicos randomizados foram responsáveis por cerca de 10% de todas as publicações. Observou-se um aumento das evidências de alta qualidade e uma diminuição das publicações de baixa qualidade durante o período (P = 0,036). A confiabilidade entre avaliadores demonstrou concordância significativa para níveis de evidência.CONCLUSÕES: Um aumento nas evidências de alto nível, assim como no número absoluto de artigos em sistema nervoso central foi claramente demonstrado, apesar de o número global ser ainda relativamente pequeno.

CONTEXT AND OBJECTIVE: To the best of our knowledge, there has been no systematic assessment of the classification of scientific production within the scope of radiation oncology relating to central nervous system tumors. The aim of this study was to systematically assess the status of evidence relating to the central nervous system and to evaluate the geographic origins and major content of these published data.DESIGN AND SETTING: Descriptive critical appraisal study conducted at a private hospital in São Paulo, Brazil.METHODS: We evaluated all of the central nervous system studies published in the journal Radiotherapy & Oncology between 2003 and 2012. The studies identified were classified according to their methodological design and level of evidence. Information regarding the geographical location of the study, the institutions and authors involved in the publication, main condition or disease investigated and time of publication was also obtained.RESULTS: We identified 3,004 studies published over the 10-year period. Of these, 125 (4.2%) were considered eligible, and 66% of them were case series. Systematic reviews and randomized clinical trials accounted for approximately 10% of all the published papers. We observed an increase in high-quality evidence and a decrease in low-quality published papers over this period (P = 0.036). The inter-rater reliability demonstrated significant agreement between observers in terms of the level of evidence.CONCLUSIONS: Increases in high-level evidence and in the total number of central nervous system papers were clearly demonstrated, although the overall number of such studies remained relatively small.

Resumo O objetivo do presente estudo é descrever a biogênese do microRNA, suas relações na carcinogênese e a correlação do microRNA com a radiação ionizante (RI), com enfoque na radiorresponsividade. Observou-se que a biogênese do microRNA está bem estabelecida e envolve diversas clivagens enzimáticas que resultam na produção do microRNA maduro. Os microRNAs estão envolvidos na carcinogênese. Sua interação está relacionada às alterações genéticas e epigenéticas, associadas à ativação de proto- -oncogenes ou à inativação de genes supressores de tumor. Vários estudos demonstraram que os níveis de expressão de alguns microRNAs variam significativamente após a irradiação. Há evidências de que os microRNAs podem influenciar a resposta celular após a RI. Além disso, os microRNAs estão relacionados à modulação da expressão de vários alvos de pós-transcrição das vias de resposta aos danos no DNA e o do mecanismo de regulação de reparação de danos do DNA. Estudos futuros podem elucidar uma possível utilização clínica dos microRNAs como uma nova classe de agentes radiossensíveis.

Summary The aim of this study is to describe the biogenesis of microRNA, its relations with carcinogenesis, and the correlation between microRNA and ionizing radiation (IR), focusing on radioresponsiveness. It is known that microRNA biogenesis is well established and involves different enzymatic cleavages, resulting in the production of mature microRNA. MicroRNAs are involved in carcinogenesis. Their interaction is related to the genetic and epigenetic changes associated with activation of proto-oncogenes or inactivation of tumor suppressor genes. Several studies have shown that the levels of expression of some microRNAs vary significantly after irradiation. There are evidences that microRNAs can influence cellular response after IR. In addition, microRNAs are related to modulation of the expression of several post-transcriptional targets in DNA damage response pathways, and to the DNA damage repair regulation mechanism. Future studies can clarify a possible clinical use of microRNAs as a new class of radiosensitive agents.