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)

Clinical outcomes of perioptic tumors treated with hypofractionated stereotactic radiotherapy using CyberKnife® stereotactic radiosurgery.

INTRODUCTION: Stereotactic radiation technique is widely reported as an effective treatment for various types of benign intracranial tumors. However, single fraction radiosurgery (SRS) is not recommended for tumors located close to the optic apparatus due to the restricted radiation tolerance dose of the optic pathway. Recent advances in radiotherapy include advanced frameless radiosurgery using hypofractionated stereotactic radiotherapy (HSRT), and this has become an attractive treatment option for perioptic tumors within 2-3 mm of the optic pathway. Accordingly, the aim of this study was to investigate the clinical outcomes of perioptic tumors treated with HSRT using CyberKnife® (CK) robotic radiosurgery system relative to tumor control, vision preservation and toxicity. METHODS: This retrospective analysis of prospectively collected data included consecutive 100 patients that were diagnosed with and treated for perioptic tumor at the Radiosurgery center, Ramathibodi Hospital during the January 2009 to December 2012 study period. RESULTS: The median tumor volume was 6.81 cm3 (range 0.37-51.6), and the median prescribed dose was 25 Gy (range 20-35) in 5 fractions (range 3-5). After the median follow-up time of 37.5 months (range 21-103), two patients developed tumor progression at 6 and 34 months post-HSRT. The 5-year overall survival was 97%, and the 5-year local control was 97.5%. At the last follow-up, no vision deterioration or newly developed hypopituitarism was detected in our study. CONCLUSIONS: Although a longer follow-up is needed, HSRT yields a high level of local control and vision preservation, and should be considered a treatment of choice for perioptic tumor located close to the optic apparatus.

[Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy].

PURPOSE: Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. PATIENTS AND METHODS: Between December 2011 and January 2013, 34 patients(19 males, 15 females;age range, 3-80 years)received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting(grade 1)or nausea(grade 2)were treated with granisetron as a rescue anti-emetic. Episodes were graded as(1)no vomiting, no nausea, no anti-emetic;(2)no vomiting, nausea, no anti-emetic;(3)no vomiting, nausea with anti-emetic;and(4)vomiting. RESULTS: Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5(55.6%)experienced grade 2 nausea or vomiting. Two of 6 patients(33.3%)treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients(16.7%)who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia(p<0.05). Complete response(no vomiting, no additional rescue anti-emetic, and no nausea)was observed in 5 of 9 patients treated with granisetron. Four of 9 patients(44.4%)treated with granisetron experienced constipation(grade 1 or 2);its administration had no major adverse effects in our study population. CONCLUSION: Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation.

Radiation therapy in neurologic disease.

Radiotherapy is a primary mode of treatment of many of the disease entities seen by the neurologist. Therefore knowledge of how ionizing radiation works and when it is indicated is a crucial part of the field of Neurology. The neurologist may also be confronted with some of the side effects and complications or radiotherapy treatment. This chapter attempts to serve as a review of the current day process of radiotherapy, a brief review of biology and physics of radiation, and how it is used in the treatment diseases which are common to the Neurologist. In addition we review the more commonly seen side effects and complications of treatment which may be seen by the neurologist.

Multidisciplinary approach in the treatment of malignant paraganglioma of the glomus vagale: a case report.

Malignant paraganglioma of the glomus vagale is a rare tumor entity originating from paraganglia or glomus cells. It typically affects middle age. It differs from benign paraganglioma because of its rapid growth and more aggressive clinical behavior. We report the case of a 40-year-old man presenting with a 5 cm lesion in the upper right cervical region detected by computed tomography (CT) and magnetic resonance imaging (MRI), which also showed enlargement of ipsilateral spinal and jugulodigastric lymph nodes with contrast enhancement. Clinical manifestations at diagnosis included a partial neurological deficit involving the right cranial nerves X, XI and XII. Tumor vascularization was assessed by digital angiography. The tumor mass was entirely removed by a right cervical approach with en-bloc resection with the regional lymph nodes. Histopathological examination showed a paraganglioma with cellular pleomorphism, necrotic microfoci, perineural infiltration and angiogenesis. Massive metastases in two of three jugulodigastric and one spinal lymph nodes on the right side were also detected. Postoperative workup included MRI, positron emission tomography (PET)/CT, meta-iodine-benzyl-guanidine (MIBG) scan, liver ultrasound and chest radiography. Subsequently, the patient underwent conformal radiotherapy with concomitant cisplatin administration. At the last clinical and radiological follow-up examination 5 years after completion of treatment, the patient was free of tumor recurrence. The integrated treatment by surgery and chemoradiation was feasible and effective in the management of this rare case of malignant paraganglioma of the glomus vagale. Multicenter studies should be done to increase the knowledge of tumor presentation and natural history and to analyze the possible treatment options.

[Glioblastoma treatment in 2010]. / Traitement des glioblastomes à l'aube de 2010.

The treatment of glioblastomas requires a multidisciplinary approach because despite the progresses in surgical and iconographic managements associated with research knowledge this disease presently remains incurable and progresses during the 6 months after its diagnose. Current recommendations are that patients with glioblastoma should undergo maximum surgical resection followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide, followed subsequently by additional adjuvant temozolomide for a period of up to 6 months. Temozolomide mechanism of action is complex and we have recently evidenced a temozolomide-associated anti-angiogenic activity in vitro and in vivo on preclinical human glioblastoma models. We describe in the current review the temozolomide-associated antiangiogenic activity. We also describe here the major signaling pathways that can be constitutively activated in migrating glioma cells, and which render these cells resistant to proapoptotic insults such as conventional chemotherapies. In light of this resistance, we therefore describe the targeted therapies and local drug delivery systems which could be used to complement conventional treatments. We have reviewed more than 400 ongoing clinical trials with respect to these new targeted therapy approaches alone or in combination for glioblastoma therapy and we also emphasize the importance of vaccinotherapy. We conclude our review with a therapeutic model that could be used in the light of the present knowledge.

Curability of cancer by radiotherapy and chemotherapy, including in neuraxial neoplasms.

In the October of 1996, Lance Armstrong, celebrated cyclist and one of the greatest athletes the world has ever seen, at the age of 24, was diagnosed with metastatic testicular cancer with disease having already spread to his abdomen, lungs and brain. Lance underwent four cycles of chemotherapy, actually the pretty standard one, pioneered at the Indiana University and not only did he get completely cured of his cancer, he remains extremely well till date, 12 years later. He sure did have a few adverse effects during those cycles of chemotherapy in the form of nausea, vomiting, weakness and fall in blood count but he knew and experienced them only for a short transient time and emerged triumphant and strong. In fact, he went on to win six awe-inspiring and incredible successive Tours de France victories from 1999-2005, one of the most grueling sporting events testing the endurance of the very fittest. After his retirement, he has been so inspired that he has completely devoted himself to educate people about the common myths about cancer, and promised to raise awareness and generate money for furthering research into surgery, radiation therapy and chemotherapy for cancer through his foundation. He says "I am indebted to the doctors, nurses and medicine and would want to pay them back for all their energy and caring." In his successful journey of overcoming cancer, he captures the essence of its treatment so well by declaring "Pain is temporary, it may last a minute, or an hour, or a day, or a year, but eventually, it will subside and something else will take its place. If I quit, however, it will last forever".

A dosimetry intercomparison phantom for intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) using very low kV x-rays is a promising new treatment modality and has proven to be effective for managing breast and neurological tumours. We have treated in excess of 75 patients using four Zeiss Intrabeam x-ray sources (XRS). To date there has been no published data of any dosimetric intercomparison of this type of x-ray source used at other cancer centres worldwide. This paper describes the design of a simple dosimetry intercomparison phantom for use with these very low kV x-ray sources. A prototype polymethyl methacrylate (PMMA) phantom has been manufactured, the dimensions of which were determined by the dimensions of the XRS, the beam energy and the attenuating properties of PMMA. The phantom is used in conjunction with Gafchromic XR Type-R film (GC-XRR) and its purpose is to measure the absorbed dose at a fixed distance from the effective point source at the tip of the XRS. The utility of this phantom is further enhanced through the use of an interlock, which eliminates the need to use the mobile gantry. We have used this phantom to conduct a qualitative dosimetric intercomparison of four Zeiss Intrabeam x-ray sources with positive results. This phantom is low cost, easy to manufacture, simple to use and could be adopted as a standard method of dosimetric intercomparison for Intrabeam x-ray sources as this mode of IORT becomes more widespread.

Automated gamma knife radiosurgery treatment planning with image registration, data-mining, and Nelder-Mead simplex optimization.

Gamma knife treatments are usually planned manually, requiring much expertise and time. We describe a new, fully automatic method of treatment planning. The treatment volume to be planned is first compared with a database of past treatments to find volumes closely matching in size and shape. The treatment parameters of the closest matches are used as starting points for the new treatment plan. Further optimization is performed with the Nelder-Mead simplex method: the coordinates and weight of the isocenters are allowed to vary until a maximally conformal plan specific to the new treatment volume is found. The method was tested on a randomly selected set of 10 acoustic neuromas and 10 meningiomas. Typically, matching a new volume took under 30 seconds. The time for simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and 8/10 meningiomas, the automatic method found plans with conformation number equal or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10 meningiomas, both overtreatment and undertreatment ratios were equal or better in automated plans. In conclusion, data-mining of past treatments can be used to derive starting parameters for treatment planning. These parameters can then be computer optimized to give good plans automatically.

Cell proliferative activity estimated by histone H2B mRNA level correlates with cytogenetic damage induced by radiation in human glioblastoma cell lines.

We studied the relationship between proliferative activity and radiation-induced DNA damage in human malignant gliomas in vitro. Nine human glioblastoma established cell lines were gamma-irradiated (60Co) over a dose range of 0-10 Gy. H2B and H4 histone mRNA level was assessed with quantitative RT-PCR technique (TaqMan) and histone labeling index (HLI) with in situ hybridization to define proliferation rate, while cytochalasin-block micronucleus assay was performed to measure cytogenetic damage. Micronucleus frequency correlated with H2B mRNA level (Spearman's R up to 0.82 at 8 Gy), HLI, nuclear division index (NDI) and percentage of binucleated cells (%BNC). There was a high correlation between H2B mRNA level and NDI (R = 0.80) as well as %BNC and HLI (R = 0.72). Histone H2B and H4 mRNA level (not significant), HLI, NDI, and %BNC (significant) were higher in cell lines sensitive to DNA damage. Proliferative activity correlates with radiation-induced DNA damage in human glioma cell lines. Histone H2B mRNA level and HLI may be a useful molecular predictor of the tumour response to radiation treatment in gliomas of the same histological grade, however the risk of potentially more rapid tumour-cell repopulation must be considered. Presumed protective activity of histones against radiation-induced DNA damage was not confirmed at the transcript level.

Toxicidad y tratamientos de soporte en oncología radioterápica. Tórax y sistema nervioso central. Riesgo/beneficio de las terapias asociadas / No disponible

No disponible

Bases radiobiológicas de la asociación de fármacos y radioterapia en los tumores del sistema nervioso central

No disponible

Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.

BACKGROUND: Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. We undertook a systematic review and meta-analysis to assess the effects of such treatment on survival and recurrence. METHODS: We did a systematic review and meta-analysis using updated data on individual patients from all available randomised trials that compared radiotherapy alone with radiotherapy plus chemotherapy. Data for 3004 patients from 12 randomised controlled trials were included (11 published and one unpublished). FINDINGS: Overall, the results showed significant prolongation of survival associated with chemotherapy, with a hazard ratio of 0.85 (95% CI 0.78-0.91, p<0.0001) or a 15% relative decrease in the risk of death. This effect is equivalent to an absolute increase in 1-year survival of 6% (95% CI 3-9) from 40% to 46% and a 2-month increase in median survival time (1-3). There was no evidence that the effect of chemotherapy differed in any group of patients defined by age, sex, histology, performance status, or extent of resection. INTERPRETATION: This small but clear improvement in survival from chemotherapy encourages further study of drug treatment of these tumours.

Unusual eustachian tube mass: glomus tympanicum.

SUMMARY: A case of recurrent glomus tympanicum presenting with epistaxis is described. CT and MR imaging revealed a homogeneously enhancing mass extending along the entire course of the eustachian tube, with a portion protruding into the nasopharynx. Glomus tumors tend to spread along the path of least resistance and may extend into the eustachian tube. The unique imaging appearance should place a glomus tumor high on the list of differential diagnoses.

Advances in pediatric neuro-oncology.

A number of exciting advances have been reported over the past few years in the understanding and treatment of children with brain tumors. The present review highlights many of the publications from this period, focusing on their relevance within the major diagnostic and treatment domains of pediatric oncology (surgery, radiation therapy, chemotherapy, neuropathology, and neuroradiology). Although many of the publications cited provide confirmation of previously reported work, when taken together they form a good framework of the state of the field from the past few years.

Tumores do sistema nervoso central / Tumors of the central nervous system

A autora destaca a importância dos tumores do sistema nervoso central em Pediatria, visto tratar-se do segundo grupo de neoplasias em frequência. Estuda os gliomas de alto e baixo grau de malignidade, os astrocitomas cerebelares, gliomas supratentoriais e de linha média, de vias ópticas e do tronco cerebral, o meduloblastoma e os tumores da regiäo pineal, analisando seu quadro clínico, diagnóstico, evoluçäo e tratamento

Primary malignant schwannoma involving simultaneously the right Gasserian ganglion and the distal part of the right mandibular nerve. Case report.

A 66-year-old man presented to our Department with trigeminal neuralgia of the third division of the right trigeminal nerve. He also complained of some difficulty in mastication because of a tumour mass in the right lower jaw. A brain CT scan, X-rays of the lower jaw and viscerocranium CT scan revealed a malignant schwannoma of the right Gasserian ganglion involving simultaneously the distal end of the right mandibular nerve. The patient was operated on and has undergone a course of external irradiation. Seven years later, he is living a normal life. The value of the preoperative diagnosis of this extremely rare pathology is discussed because it seems that this tumour is radiosensitive.

Carcinoma insular de tiroides: reporte de un caso de revisión de la literatura / Insular carcinoma of the thyroid: report of 1 case and review of the literature

El carcinoma insular de tiroides es un tumor poco frecuente. Fue descrito originalmente en 1907. Hasta la fecha, en la literatura mundial se ha informado de altededor de 100 casos. La importancia del carcinoma insular de tiroides resalta cuando se revisa la clasificación de tumores de tiroides. Para este fin se puede observar que las clasificaciones vigentes emplean una correlación clinicopatológica en la que se relaciona a las diversas morfologías conocidas con una conducta específica conocida. Con este concepto en mente podemos considerar neoplasias de relativamente buen pronóstico, como los carcinomas papilar y folicular de tiroides, y tumores de mal pronóstico, como el carcinoma anaplásico, como el carcinoma anaplásico de tiroides. De manera semejante tendríamos que considerar a los tumores poco diferenciados como formas intermedias entre los tipos descritos. El carcinoma insular de tiroides corresponde a una variante poco diferenciada, con potencial metastásico elevado., con una supervivencia menor a la de las formas diferenciadas de tumores malignos de tiroides, pero menos agresivo que los tumores anaplásicos de el mismo órgano. En el presente artículo presentamos un caso de carcinoma insular de tiroides y una revisión de la literatura relacionada con el tema