Consenso chileno para el diagnóstico y tratamiento de gliomas del adulto / Diagnosis and treatment of glioma in adult: Chilean consensus

Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.

Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.

Primary Extra-axial Glioblastoma: Case Report and Literature Review

Glioblastoma multiforme (GBM) is the most frequent and most aggressive primary brain tumor in adults,mainly located in the cerebral hemispheres. In the literature, few cases of primary GBM have been reported to have radiographic and intraoperative features of extra-axial lesions, leading to a diagnostic dilemma. Despite the advances in imaging modalities, the diagnosis of GBM can be challenging, and it is mainly based on the histopathologic confirmation of the excised tumor. We describe the case of a 76- year-old previously healthy female patient who presented to our hospital due to speech disturbances and cognitive impairment. The diagnosis of the tumor type on magnetic resonance imaging (MRI) was difficult, as the findings were suggestive of a malignant meningioma due to the heterogeneous enhancement of a dural-based mass with a dural tail sign. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. A histological examination confirmed the diagnosis of glioblastoma with arachnoid infiltration. The patient underwent adjuvant radiotherapy and concomitant temozolomide treatment, she had clinical improvement postoperatively, and was stable during the six months of follow-up. Glioblastoma should be considered in the differential diagnosis of primary extra-axial mass with atypical and malignant features, especially in elderly patients.

Comprehensive quality assurance for intracranial radiosurgery treatments using a postal system / Garantía de calidad para tratamientos de radiocirugía intracranial usando un sistema postal

Radiosurgery is a high-precision technique for delivering, in most cases, a single highly conformal dose to a stereotactically localized target. It can be indicated for small intracranial injury treatment, using either multiple sources of 60Co (γ rays) or high energy photon beams produced by linear accelerators. In order to minimize the impact of inaccurate localization of the target or dose delivery, a rigorous Quality Assurance (QA) program must be enforced, which should include an independent auditing system. This work proposes a simple and reliable postal QA phantom to be used as an independent evaluation. In it two important parameters were verified such as, the dosimetric precision of the planning system, by comparing the absorbed doses measured in the target volume using different dosimeters (ionization chamber, films, thermoluminescent dosimeters and L-alanine dosimeters) all calibrated against a small volume ion chamber. The exact positioning of the target volume was localized using air spaces and small steel spheres to find the appropriate target coordinates. The head phantom and the instruction sheets were extensively tested and sent by mail to selected institutions. The overall results were very encouraging and suggest that the proposed phantom may be used as a postal system as part of an independent QA tool in radiosurgery.

La radiocirugía es una técnica de alta precisión para administrar, en la mayoría de los casos, una sola dosis altamente conformada en un objetivo localizado estereotípicamente. Puede estar indicado para el tratamiento de pequeñas lesiones intracraneales, utilizando múltiples fuentes de 60Co (rayos γ) o haces de fotones de alta energía producidos por aceleradores lineales. Con el fin de minimizar el impacto de la ubicación inexacta de la administración de la meta o de la dosis, se debe aplicar un riguroso programa de control de calidad (QA), que debe incluir un sistema de auditoría independiente. Este documento propone un fantoma postal de control de calidad simple y fiable que se utilizará como evaluación independiente. Se verificó dos parámetros importantes, como la precisión dosimétrica del sistema de planificación, comparando las dosis absorbidas medidas en el volumen objetivo mediante diferentes dosis (cámara de ionización, películas, dosímetros Termoluminiscentes y dosímetros de L-alanina) todos calibrados con una pequeña cámara de iones de volumen. El posicionamiento exacto del volumen objetivo se localizó utilizando espacios aéreos y pequeñas esferas de acero para encontrar las coordenadas de destino adecuadas. El fantoma principal y las hojas de instrucciones fueron ampliamente probados y enviados por correo a instituciones seleccionadas. Los resultados generales fueron muy alentadores y sugieren que el fantoma propuesto puede utilizarse como sistema postal como parte de una herramienta independiente de control de calidad en radiocirugía.

Características sociodemográficas en cuidadores principales de pacientes operados de cáncer de cerebro / Socio-demographic characteristics in primary caregivers of patients with brain cancer surgery

RESUMEN Introducción: la atención al enfermo es llevada a cabo por una secuencia específica de la familia, por lo que esta es considerada un cuidador principal. Objetivo: describir las características sociodemográficas en cuidadores principales de pacientes operados de cáncer de cerebro. Materiales y métodos : se realizó un estudio descriptivo, retrospectivo, en un universo de 128 cuidadores principales de pacientes operados de cáncer de cerebro en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, entre 2016 y 2018. Criterio de inclusión: cuidadores que residían en la provincia y aceptación del consentimiento informado. Se excluyeron familiares de pacientes que fallecieron durante la investigación. Se aplicaron cuestionarios y entrevistas para caracterizar los resultados. Los mismos se analizaron en frecuencias absolutas, relativas, porcentual, en paquete estadístico de SPSS versión 20.0 en Windows. Resultados : predominó el sexo femenino (79,68 %). El 100 % de los cuidadores principales residían en casa del enfermo. Prevaleció el nivel de escolaridad de técnico medio (35,93 %); 88,28 % de los cuidadores mantenían vínculo laboral, y 41,40 % eran hermanas de los enfermos. Dentro de las necesidades de aprendizaje del cuidador, el déficit de conocimientos sobre la enfermedad constituyó el 73,43 %. Conclusiones: imperó el género femenino en los cuidadores con vínculo laboral, y con mayor incidencia las hermanas. Se evidenció la complejidad del cuidado en el hogar de los pacientes con secuelas, minusvalía progresiva producidas por la enfermedad, y que generalmente la mujer asume con más facilidad (AU).

ABSTRACT Introduction: the care of the patient is carried out by a specific sequence of the family, catalogued as a main caregiver. Objective: to describe the socio-demographic characteristics in main caregivers of patients who underwent a brain cancer surgery. Materials and methods: a retrospective, descriptive study was carried out in a universe of 128 main caregivers of patients who underwent brain cancer surgery in the University Hospital Faustino Perez Hernandez, of Matanzas, from 2016 until 2018. Inclusion criteria: caregivers living in the province of Matanzas and giving the informed consent. The relatives of patients who died during the research were excluded. Interviews were made and questionnaires applied to characterize the results. They were analyzed in absolute, relative, and percentage frequencies in statistical packet Windows SPSS, 20.0. Results: female sex predominated (79.68%). 100% of main caregivers lived in the house of the patient. The technician scholarship predominated (35.93%); 88.28% of the caregivers kept their employment bonds, and 41.40% were patients' sisters. The deficit of knowledge on the disease was 73.43% of the caregiver learning necessities. Conclusions: female genre prevailed in caregivers with employment bonds, with higher incidence of sisters. It was evidenced the complexity of home care of the patients with sequels, progressive disabilities caused by the disease, generally assumed more easily by women (AU).

Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

Clinical practice guideline for brain metastases of lung cancer in China (2021 version) / 中华肿瘤杂志

Brain metastases are common in lung cancer patients, indicating a poor prognosis and short survival time. In recent years, with the development of surgery, radiotherapy and medical therapy, the survival time of lung cancer patients with brain metastases has been prolonged owing to more and more treatment options. In order to reflect the progress in the treatment worldwide timely, and further improve the level of standardized treatment of lung cancer with brain metastases in China, Chinese Association for Clinical Oncologists and Medical Oncology Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare organized experts to formulate "Clinical practice guideline for brain metastases of lung cancer in China (2021 version)" .

Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Delayed Cerebral Metastasis of Breast Cancer: Case Report and Molecular Review

Breast cancer (BC) is a prevalent disease, and its incidence of brain metastasis (BM) varies from5 to 30% according to the literature.We present the case of a delayed isolated cerebral metastasis in a female patient following a period of 16 years after the diagnosis and first treatment. During this time, there was no other recurrence. We also review the literature concerning central nervous systemspread and themolecular subtypes of such late tumors.

Testicular mixed germ cell tumor presenting with seizure as the initial symptom: a case report and literature review

Abstract Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.

Brain metastasis in papillary serous adenocarcinoma of the endometrium / Metástase cerebral do adenocarcinoma seroso-papilífero do endométrio

Abstract Background Most endometrial cancers (75%) are diagnosed in early stages (stages I and II), in which abnormal uterine bleeding is the most frequent clinical sign.When the diagnosis is performed in stage IV, the most common sites of metastasis are the lungs, liver and bones. Central nervous system (CNS)metastasis is a rare condition. The aim of this study is to describe a case of uterine papillary serous adenocarcinoma of the endometrium that progressed to brain and bone metastases. Case Report We present the case of a 56-year-old woman with abnormal uterine bleeding and endometrial thickened echo (1.8 cm). A hysteroscopy with biopsy was performed, which identified poor differentiated serous adenocarcinoma of the endometrium. A total abdominal hysterectomy, with pelvic and para-aortic lymphadenectomy, was performed. Analysis of the surgical specimen revealed a grade III uterine papillary serous adenocarcinoma. Adjuvant radio/chemotherapy (carboplatin and paclitaxel-six cycles) was indicated. Sixteen months after the surgery, the patient began to complain of headaches. Brain magnetic resonance imaging demonstrated an expansile mass in the right parietal lobe, suggesting a secondary hematogenous implant subsequently confirmed by biopsy. She underwent surgery for treatment of brain metastasis, followed by radiotherapy. She died 12 months after the brain metastasis diagnosis due to disease progression. Conclusion Uterine papillary serous adenocarcinoma of the endometrium has a low propensity to metastasize to the brain. To the best of our knowledge, this is the fifth documented case of uterine papillary serous adenocarcinoma of the endometrium with metastasis to the CNS.

Resumo Fundamentos A maioria dos cânceres de endométrio (75%) é diagnosticada em estágios iniciais (estágios I e II), nos quais o sangramento uterino anormal é o sinalclínico mais frequente. Quando o diagnóstico é realizado no estágio IV, os locais mais comuns de metástase são os pulmões, o fígado e os ossos. A metástase para o sistema nervoso central (SNC) é uma condição rara. O objetivo deste estudo é descrever um caso de adenocarcinoma seroso-papilífero do endométrio que progrediu para metástases cerebral e óssea. Relato de Caso Apresentamos o caso de uma mulher de 56 anos com sangramento uterino anormal e eco endometrial espessado (1,8 cm). Foi realizada histeroscopia com biópsia que identificou adenocarcinoma seroso-papilífero pouco diferenciado do endométrio. Uma histerectomia abdominal total, com linfadenectomia pélvica e para-aórtica, foi realizada. A análise da peça cirúrgica revelou adenocarcinoma seroso-papilífero do endométrio grau III. Radioterapia adjuvante/quimioterapia (carboplatina e paclitaxel- seis ciclos) foi indicada.Dezesseismeses após a cirurgia, a paciente começou a se queixar de dores de cabeça. A ressonância magnética cerebral demonstrou uma massa expansiva no lobo parietal direito, sugerindo um implante hematogênico secundário posteriormente confirmado por biópsia. A paciente foi submetida a cirurgia para tratamento de metástase cerebral, seguida de radioterapia. A paciente morreu 12 meses após o diagnóstico de metástase cerebral devido à progressão da doença. Conclusão O adenocarcinoma seroso-papilífero do endométrio tem uma baixa propensão a metastizar para o cérebro. Até onde sabemos, este é o quinto caso documentado de adenocacinoma seroso-papilífero do endométrio com metástase para o SNC.

Therapeutic evaluation of magnetic hyperthermia using Fe3O4-aminosilane-coated iron oxide nanoparticles in glioblastoma animal model / Avaliação terapêutica da técnica de magneto-hipertermia utilizando nanopartículas de Fe3O4 recobertas com aminosilana em modelo animal de glioblastoma

ABSTRACT Objective: To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model. Methods: The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia. Results: The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence. Conclusion: The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.

RESUMO Objetivo: Avaliar o potencial da técnica de magneto-hipertermia utilizando nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana em modelo de tumores de glioblastoma. Métodos: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram avaliadas quanto à sua estabilidade em meio aquoso e a seu potencial de aquecimento pela taxa de absorção específica, quando submetidas à magneto-hipertermia, com diferentes frequências e intensidades de campo magnético alternado. Nos ensaios de magneto-hipertermia in vitro, as células C6 cultivadas e transduzidas com luciferase foram avaliadas por bioluminescência na presença/ausência do campo magnético alternado, como também com e sem nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana. No estudo in vivo, a medida de bioluminescência foi adquirida no 21º dia após indução do glioblastoma com células C6 nos ratos. Após 24 horas, as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram implantadas no animal, tendo sido realizada a magneto-hipertermia por 40 minutos, nas melhores condições de frequência e intensidade de campo magnético alternado testado no estudo in vitro (maior valor da taxa de absorção específica); foi verificada a diferença do bioluminescência antes e após a magneto-hipertermia. Resultados: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana se mostraram estáveis, e sua capacidade de aquecimento aumentou com o incremento da frequência e da intensidade de campo magnético alternado. A aplicação da magneto-hipertermia, com 874kHz e 200 Gauss do campo magnético alternado, determinou o melhor valor da taxa de absorção específica (194,917W/g). Quando utilizados, estes parâmetros de magneto-hipertermia in vitro resultaram em morte celular de 52,0% e in vivo de 32,8% por bioluminescência. Conclusão: A técnica de magneto-hipertermia foi promissora para o processo terapêutico de tumores de glioblastoma no modelo animal utilizando as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana recobertas com aminosilana, que apresentaram alta taxa de absorção específica.

Nimotuzumab y radioterapia en el tratamiento de tumores del tallo cerebral en niños y adolescentes / Nimotuzumab and radiotherapy in the treatment of brainstem tumors in children and adolescents

Introducción: Los tumores localizados en el tallo cerebral en los niños y adolescentes conllevan un mal pronóstico, especialmente aquellos infiltrantes y difusos. Con el tratamiento de radioterapia apenas llegan a más de 15 por ciento de supervivencia y no mejora la cifra con quimioterapia agregada. Objetivos: Estimar el efecto de la asociación del tratamiento radiante con el anticuerpo monoclonal Nimotuzumab en la supervivencia de niños y adolescentes con tumores del tallo cerebral. Método: Estudio clínico no aleatorizado, analítico, longitudinal y prospectivo. Se estudió una serie de 46 pacientes entre 2 y 18 años de edad que padecían de tumores del tallo cerebral, infiltrantes y difusos, desde enero de 2008 y en seguimiento hasta marzo de 2018. Todos se trataron con radioterapia, con dosis entre 54 y 59,8 cGrey, dosis diaria de 1,8 cGrey, y se irradiaban de lunes a viernes. Mientras duró el tratamiento radiante recibieron Nimotuzumab, en la dosis de 150 mg/m2 de superficie corporal, luego semanal con 8 dosis, y finalmente mensual durante uno o dos años. Resultados: Se alcanzó en la serie una supervivencia media de 18,4 meses, y una esperada de 42,9 por ciento a 2 años y 35,5 por ciento a 5 años, estabilizada hasta los 10 años. Conclusiones: La combinación de radioterapia y el anticuerpo monoclonal Nimotuzumab incrementa la supervivencia en niños y adolescentes con tumores del tallo cerebral y es bien tolerada, aun en periodos prolongados, e incluso en casos de recidiva(AU)

Introduction: Tumors localized in the brainstem of children and adolescents entail a bad prognosis, especially those that are intrinsic and diffuse. With radiotherapy treatment, patients barely get a 15 percent of survival, and the numbers don't improve with added chemotherapy. Objectives: To estimate the effect of the association of radiotherapy treatment with Nimotuzumab monoclonal antibody in the survival of children and adolescents with brainstem tumors. . Method: Non randomized, analytical, longitudinal and prospective clinical study that was authorized by the National Regulatory Authority. There was studied a group of 46 patients aged from 2 to 18 years that suffered from intrinsic and diffuse brainstem tumors, from January 2008 (and in follow up) to March 2018. All the patients were treated with radiotherapy, with doses among 54 and 59,8 Grey, daily doses of 1,8 Grey, and from Monday to Friday. While they were under radiotherapy treatment, they get Nimotuzumab, in doses of 150 mg/m2 of corporal surface; then weekly doses of 8 shots; and finally, monthly doses during one or two years. Results: In this group there was a survival mean of 18, 4 months, and an expected survival of 42, 9 percent for 2 years and 35, 5 percent for 5 years that can be stabilized to 10 years. Conclusions: Combination of radiotherapy and Nimotuzumab monoclal antibody can increase the survival from brainstem tumors in children and adolescents(AU)

Analysis of survival in patients with brain metastases treated surgically: Impact of age, gender, oncologic status, chemotherapy, radiotherapy, number and localization of lesions, and primary cancer site

SUMMARY OBJECTIVE To evaluate the survival of patients with brain metastases treated surgically according to the potentially involved factors. METHODS 71 patients treated surgically were analyzed with the diagnosis of brain metastases during the period from January 2011 to November 2014, totaling 47 months of follow-up. The Kaplan-Meier curve method was used for survival analysis. Results We evaluated 71 patients with brain metastases treated surgically, 44 female and 27 male, mean age of 60.1 years. According to the Karnofsky scale, 44 patients were classified with Karnofsky greater than or equal to 70 and 27 patients with Karnofsky inferior to 70. Lung was the primary site most commonly found. Death occurred in twenty patients (28%), and lung tumors were responsible for the most deaths. Twelve patients had supra and infratentorial metastases, fifty-nine only had supratentorial lesions, and lesions were multiple in twenty-eight patients and single in forty-three. Thirty patients were also treated with chemotherapy, eighteen with chemotherapy and radiation therapy, while only three received just radiotherapy. Survival analysis by Kaplan-Meier curve showed no statistical significance regarding age, histological type, location, Karnofsky, chemotherapy, and radiotherapy. There was statistical significance regarding gender. CONCLUSION The factors analyzed did not change survival rates, except for gender. This fact may probably be explained due to the systemic and diffuse behavior of cancer.

RESUMO OBJETIVO Avaliar a sobrevivência de pacientes com metástases cerebrais tratados cirurgicamente de acordo com os fatores potencialmente envolvidos. Métodos 71 pacientes tratados cirurgicamente foram analisados com o diagnóstico de metástases cerebrais durante o período de janeiro de 2011 a novembro de 2014, totalizando 47 meses de seguimento. A curva de Kaplan-Meier foi utilizada para análise de sobrevivência. Resultados Avaliamos 71 pacientes com metástases cerebrais atendidas cirurgicamente, 44 do sexo feminino e 27 do sexo masculino, idade média de 60,1 anos. De acordo com a escala de Karnofsky, 44 pacientes foram classificados com Karnofsky maior ou igual a 70 e 27 pacientes com Karnofsky com menos de 70. O pulmão era o local mais comum. A morte ocorreu em 20 pacientes (28%) e os tumores pulmonares são responsáveis pela maioria das mortes. Doze pacientes apresentavam metástases supra e infratentoriais, 59 apresentavam apenas lesões supratentoriais, e as lesões eram múltiplas em 28 pacientes e isoladas em 43. Trinta pacientes também foram tratados com quimioterapia, 18 foram tratados com quimioterapia e radioterapia, enquanto que apenas três receberam apenas radioterapia. A análise de sobrevivência pela curva de Kaplan-Meier não mostrou significância estatística de acordo com a idade, tipo histológico, localização, Karnofsky, quimioterapia e radioterapia. Houve significância estatística em relação ao gênero. Conclusão Os fatores analisados não alteraram a sobrevivência, exceto o gênero. Este fato provavelmente pode ser explicado devido ao comportamento sistêmico e difuso do câncer.

Genetic variants related to angiogenesis and apoptosis in patients with glioma / Variantes genéticas relacionadas à angiogênese e apoptose em pacientes com glioma

ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

RESUMO Introdução Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]). Métodos 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05. Resultados Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711). Conclusões As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doença. O tratamento com TMZ + RT mostrou aumento na sobrevida dos pacientes.

Actualización del manejo de metástasis encefálicas / Metastasis management update encephalic

Brain metastases represent a critical stage of oncological disease and its frequency is increasing over the recent years. The treatment of brain metastases has moved from a conservative approach to an active management that should be individualized for each patient: in case of single brain metastasis, surgery or radiosurgery should be considered as first option of treatment; in case of multiple lesions, whole-brain radiotherapy is the standard of care. The aim of this review is to present general aspects including new approaches in management of patients with brain metastases.(AU)

Performance of adjuvant treatment correlates with survival in reoperated glioblastomas / Uso de tratamento adjuvante é relacionado ao aumento da sobrevida em pacientes com glioblastoma submetidos à reoperação

ABSTRACT Objective To analyze cases of recurrent glioblastoma subjected to reoperation at a Brazilian public healthcare service. Methods A total of 39 patients subjected to reoperation for recurrent glioblastoma at the Department of Neurosurgery, São Paulo Hospital, Federal University of São Paulo, from January 2000 to December 2013 were retrospectively analyzed. Results The median overall survival was 20 months (95% confidence interval – CI = 14.9–25.2), and the median survival after reoperation was 9.1 months (95%CI: 2.8–15.4). The performance of adjuvant treatment after the first operation was the single factor associated with overall survival on multivariate analysis (relative risk – RR = 0.3; 95%CI = 0.2–0.7); p = 0.005). Conclusion The length of survival of patients subjected to reoperation for glioblastoma at a Brazilian public healthcare service was similar to the length reported in the literature. Reoperation should be considered as a therapeutic option for selected patients.

RESUMO Objetivo Analisar o papel da reoperação em pacientes com glioblastoma recidivado em um serviço público no Brasil. Métodos Foram analisados retrospectivamente 39 pacientes submetidos à reoperação por recorrência de glioblastoma no Departamento de Neurocirurgia da Universidade Federal de São Paulo, no período de janeiro de 2000 até dezembro de 2013. Resultados A sobrevida global mediana foi de 20 meses (IC 95% = 14.9–25.2), e a sobrevida mediana após a reoperação foi de 9.1 meses (IC 95% = 2.8–15.4). A realização de tratamento adjuvante após a primeira cirurgia foi o único fator associado com a sobrevida global numa análise multivariada (RR = 0.3; IC 95% = 0.2–0.7; p = 0.005). Conclusão A sobrevida dos pacientes submetidos à reoperação em um serviço público no Brasil é semelhante à reportada pela literatura. A reoperação deve ser considerada como uma opção terapêutica em pacientes selecionados.

Educational program on fatigue for brain tumor patients: possibility strategy? / Programa educativo para fadiga em pacientes com tumor cerebral: possibilidade de estratégia?

ABSTRACT Objective To evaluate the effectiveness of an educational program on improvement of fatigue and quality of life of patients with high-grade glioma during radiotherapy and chemotherapy treatment. Method This is a longitudinal, experimental study. Twenty-three patients with high-grade glioma were randomly assigned to one of two groups. Both groups completed the Functional Assessment of Cancer Therapy: Fatigue questionnaire and the Beck Depression Inventory, and one of the groups received the educational intervention. The groups did not show any change in quality of life and fatigue in this study, for this reason, the educational program did not present any significant difference. However, there was a significant difference in depressive symptoms during the educational program showing positive evidence for its applicability.

RESUMO Objetivo Verificar a efetividade de um programa educativo na melhora da fadiga e dos sintomas depressivos em pacientes com glioma de alto grau durante o tratamento com radioterapia e quimioterapia. Método Trata-se de estudo longitudinal e experimental. Foram incluídos 23 pacientes com glioma de alto grau e divididos aleatoriamente em 2 grupos. Os dois grupos responderam os questionários Functional Assessment of Cancer Therapy: Fatigue e Inventário de Depressão de Beck, porém somente um foi inserido ao programa educativo. Resultados e Conclusões Os grupos não apresentaram alteração na fadiga ao longo desse estudo, assim o programa educativo não mostrou diferença significativa, porém nos sintomas depressivos, o programa educativo trouxe diferença quando estava sendo realizado mostrando evidências positivas para sua aplicabilidade.

Gliosarcoma cerebeloso asociado aneurofibromatosis tipo I: presentación de caso / Cerebellar gliosarcoma associated with neurofibromatosis type I: case presentation

El Gliosarcoma es un raro Glioblastoma que contiene tantos elementos gliales comparable con un Glioblastoma como componentes mesenquimal. Aproximadamente entre 2-8% de todos los Glioblastomas están asociados con elementos sarcomatosos. Clínica y genéticamente muy parecido a los Glioblastomas, excepto por la ausencia de amplificación del EGFR. El gliosarcoma es un tumor de alto grado de malignidad y pobre pronóstico, con alta tasa de recurrencia. Presentamos el caso de un paciente masculino de 54 años de edad con diagnóstico de gliosarcoma cerebeloso, asociado a Neurofibromatosis tipo I. La NF I es el síndrome hereditario más común que predispone a la neoplasia, es una enfermedad polifacética asociado no sólo a tumores benignos.

Gliosarcoma are rare glioblastomas that contain an anaplastic glial component comparable to a glioblastoma, as well as,a mesenchymal component, that have a biphasic pattern. Approximately 2-8% of all glioblastomas are associated with a sarcomatous element. Clinically and genetically close to glioblastomas, except for the absence of EGFR amplification. The Gliosarcoma is a high-grade tumor of malignity and poor prognosis, with high rate of recurrence. We present the case of a masculine patient of 54 elderly years, with diagnosis of Gliosarcoma Cerebellar associate to Neurofibromatosis type I. The NF I is the hereditary syndrome more common that predisposes to the tumor, it is a versatile disease that not only becomes a partner of benign tumors.

EGFR, p53, IDH-1 and MDM2 immunohistochemical analysis in glioblastoma: therapeutic and prognostic correlation / Análise imunoistoquímica para EGFR, p53, IDH-1 e MDM2 em glioblastoma: correlação terapêutica e prognóstica

We studied 36 glioblastoma cases at HC-UNICAMP from 2008 to 2012 and classified the immunohistochemical distribution of the wild-type epidermal growth factor receptor (EGFR), mutated forms of p53 protein and isocitrate dehydrogenase-1 (IDH-1) and murine double protein 2 (MDM2). Immunostaining findings were correlated with clinical data and response to treatment (surgery, chemotherapy and radiotherapy). About 97% of the tumors were primary, most of them localized in the frontal lobe. Mean time free of clinical or symptomatic disease and free time of radiological disease were 7.56 and 7.14 months, respectively. We observed a significant positive correlation between expressions of p53 and MDM2, EGFR and MDM2. Clinical, radiological and overall survivals also showed a significant positive correlation. p53 staining and clinical survival showed a significant negative correlation. The current series provides clinical and histopathological data that contribute to knowledge on glioblastoma in Brazilians.

Estudamos 36 casos de glioblastoma acompanhados no HC-UNICAMP de 2008 a 2012 e classificamos a marcação imunoistoquímica da forma selvagem do receptor do fator de crescimento epidérmico (EGFR), formas mutantes da proteína p53 e isocitrato desidrogenase-1 (IDH-1) e proteína murina dupla 2 (MDM2). Os resultados de imunoistoquímica foram correlacionados com dados clínicos e resposta ao tratamento (cirurgia, quimioterapia e radioterapia). Cerca de 97% dos tumores foram primários, grande parte localizada no lobo frontal. O tempo médio livre de doença clínica ou sintomática e o tempo livre de doença radiológica foram de 7.56 e 7.14 meses, respectivamente. Observou-se correlação positiva entre a expressão das proteínas p53 e MDM2, EGFR e MDM2. Sobrevivências clínica, radiológica e global também mostraram correlação positiva e significativa. A expressão para p53 e sobrevivência clínica mostrou correlação negativa. O estudo fornece dados clínicos e histopatológicos que contribuem para o conhecimento sobre glioblastoma em brasileiros.

Tratamiento multimodal e individualizado a pacientes con metástasis encefálica / Multimodal and individualized treatment for patients with brain metastases

Introduction: The treatment of Brain Metastases is palliative and it is ignored the ideal therapeutic combination, constituting this a controversial topic. Objective: To determine the results of the treatment to patient with Brain Metastases according to different modalities. Method: It was carried out a prospective cohort study between april 2010 to april 2013 in the National Institute of Oncology and Radiobiology. It was designated as universe the total of patient with diagnosis of Brain Metastases of primary tumor assisted in consultation of Neurosurgery. The Fischer exact test was used to correlate qualitative variables and the Kaplan Meier curvesto estimate the survival. Results: It was obtained a sample of 42 patients and 84 lesions. The age average was of 53,1 years. The primary lesions prevailed in lung and breast. The used modalities were: Surgery-Whole Brain Radiation Therapy (20 lesions), Whole Brain Radiation Therapy alone (29 lesions), Radiosurgery alone (21 lesions) and Surgery alone (9 lesions). Conclusions: The combinations of Radiosurgery-Whole Brain Radiation Therapy and Surgery-Radiosurgery associated to a better local control. The treatment with Whole Brain Radiation Therapy didn't associate to a better distance control. The overall survival to the 6 months was of 91 percent and to the 12 months of 57 percent. A bigger survival was observed in patient with controlled primary illness and absence of extracraneal metastases. The Surgery presents the biggest number of complications.

Introducción: El tratamiento de la Metástasis Encefálica es paliativo y se desconoce la modalidad o combinación terapéutica óptima, constituyendo éste un tema controvertido. Objetivo: Determinar los resultados del tratamiento a pacientes con Metástasis Encefálica según diferentes modalidades. Método: Se realizó un estudio de cohorte prospectivo durante el período abril de 2010 a abril de 2013 en el Instituto Nacional de Oncología y Radiobiología. Se designó como universo el total de pacientes con diagnóstico de Metástasis Encefálica de neoplasia primaria conocida atendidos en consulta de Neurocirugía. Se utilizó el test exacto de Fischer para correlacionar variables cualitativas y las curvas de Kaplan Meier para estimar la supervivencia. Resultados: Se obtuvo una muestra de 42 pacientes y 84 lesiones. El promedio de edad fue de 53,1 años. Predominaron las lesiones primarias en pulmón y mama. Las modalidades más utilizadas fueron: Cirugía-Radioterapia Holocraneal (20 lesiones), Radioterapia Holocraneal sola (29 lesiones), Radiocirugía sola (21 lesiones) y la Cirugía sola (9 lesiones). Conclusiones: Las combinaciones de Radiocirugía-Radioterapia Holocraneal y Cirugía-Radiocirugía se asociaron a un mejor control local. El tratamiento con Radioterapia Holocraneal no se asoció a un mejor control a distancia. La supervivencia global a los 6 meses fue del 91 por ciento y a los 12 meses del 57 por ciento. Se observó una mayor supervivencia en pacientes con enfermedad primaria controlada y ausencia de metástasis extra craneal. La Cirugía presentó el mayor número de complicaciones.