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1.
Clin Cancer Res ; 25(22): 6788-6800, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31481512

RESUMO

PURPOSE: Diffuse intrinsic pontine gliomas (DIPG) are the most severe pediatric brain tumors. Although accepted as the standard therapeutic, radiotherapy is only efficient transiently and not even in every patient. The goal of the study was to identify the underlying molecular determinants of response to radiotherapy in DIPG. EXPERIMENTAL DESIGN: We assessed in vitro response to ionizing radiations in 13 different DIPG cellular models derived from treatment-naïve stereotactic biopsies reflecting the genotype variability encountered in patients at diagnosis and correlated it to their principal molecular alterations. Clinical and radiologic response to radiotherapy of a large cohort of 73 DIPG was analyzed according to their genotype. Using a kinome-wide synthetic lethality RNAi screen, we further identified target genes that can sensitize DIPG cells to ionizing radiations. RESULTS: We uncover TP53 mutation as the main driver of increased radioresistance and validated this finding in four isogenic pairs of TP53WT DIPG cells with or without TP53 knockdown. In an integrated clinical, radiological, and molecular study, we show that TP53MUT DIPG patients respond less to irradiation, relapse earlier after radiotherapy, and have a worse prognosis than their TP53WT counterparts. Finally, a kinome-wide synthetic lethality RNAi screen identifies CHK1 as a potential target, whose inhibition increases response to radiation specifically in TP53MUT cells. CONCLUSIONS: Here, we demonstrate that TP53 mutations are driving DIPG radioresistance both in patients and corresponding cellular models. We suggest alternative treatment strategies to mitigate radioresistance with CHK1 inhibitors. These findings will allow to consequently refine radiotherapy schedules in DIPG.

2.
Front Oncol ; 9: 531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293971

RESUMO

Background and purpose: Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery. Material and methods: The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]). Results: In most cases, the proton treatment resulted in higher quality indices (p < 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons (p < 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses. Conclusion: Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.

4.
Bull Cancer ; 106(9): 776-783, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31178070

RESUMO

Mucositis, an acute inflammation of the digestive mucosa, is one of the main toxicities secondary to oncological treatments. Among its consequences, mucositis-related pain is an important complication due to its intensity and repercussion, especially on quality of life. Treatment of pain plays a central role in management of mucositis. It must be multimodal, combining local and general opioid or non-opioid treatments, adapted to pain intensity and based on international recommendations updated in 2014. A systemic analgesic treatment with morphine with a patient-controlled analgesia device is often necessary in severe mucositis. In case of insufficient analgesia, use of co-analgesics (paracetamol, ketamine, anticonvulsants, and antidepressants) can improve analgesic control and reduce morphine doses. Non-drug strategies (distraction, relaxation, hypnosis) and preventive measures must be a major concern. Among them, laser therapy using a low power athermal laser beam, is a promising therapeutic strategy whose effectiveness is based on its analgesic, anti-inflammatory, and healing properties. Despite many available studies, there is a limited number of clinically effective therapies. New therapeutic agents for the prevention and treatment of mucositis and its pain, based on the biological phenomena involved, must be further developed to improve the efficacy of analgesia.


Assuntos
Analgésicos/uso terapêutico , Mucosite/complicações , Manejo da Dor/métodos , Dor/etiologia , Analgesia Controlada pelo Paciente , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Humanos , Terapia a Laser , Terapia de Alvo Molecular , Morfina/uso terapêutico , Doenças da Boca/complicações , Doenças da Boca/terapia , Mucosite/terapia , Neoplasias/terapia , Medição da Dor/métodos , Guias de Prática Clínica como Assunto
5.
Strahlenther Onkol ; 195(6): 504-516, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30963203

RESUMO

PURPOSE: The aim of this study was to retrospectively study survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC) treated by induction chemotherapy and concurrent chemoradiation (CRT). The total dose of radiation was adapted to the response following neoadjuvant chemotherapy. METHODS: Children with non-metastatic NPC treated in France between 1999 and 2015 were retrospectively included in the study. The strategy combined neoadjuvant platinum-based chemotherapy, followed by adapted CRT to tumor response. RESULTS: In total, 95 patients (median age 15 years [range, 7-23 years], male-to-female ratio 1.8) with undifferentiated NPC were included; 59% of patients had TNM stage IV. Intensity-modulated radiotherapy (IMRT) was delivered to 57 patients (60%), while the other patients were treated with conformal RT (3D-RT). After a median follow-up of 4.5 years [range, 3.6-5.5 years], 13 relapses and seven deaths had occurred. The 3­year overall and relapse-free survival (RFS) were 94% [95% CI, 85-97%] and 86% [77-92%], respectively. The locoregional failure rate was 6% [95% CI, 2-14]. Long-term treatment-related sequelae of grade 2+ were reported by 37 (50%) patients; odynophagia was significantly reduced treated by IMRT vs. conventional 3D-RT (7% vs. 55%, p = 0.015). Using a reduction dose of 59.4 Gy, 54 Gy, and 45 Gy, respectively, to the primary, involved, and uninvolved neck nodes, after a favorable tumor response, was not associated with an increased locoregional failure rate. CONCLUSIONS: The survival rates for NPC have been considerably improved by means of multimodal therapy, but long-term locoregional morbidity remains common. Use of IMRT may induce less residual odynophagia. Radiation dose reduction adapted to chemotherapy response does not have a negative impact on outcome. These findings support the use of an RT protocol adapted to the tumor response to neoadjuvant chemotherapy for a long-lasting improvement in the patient's quality of life.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , França , Humanos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
6.
Radiother Oncol ; 132: 1-7, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30825956

RESUMO

PURPOSE: This study aimed to evaluate retrospectively the clinical results of re-irradiation for children with a locally recurrent brain ependymoma. METHODS: 33 full-dose re-irradiations were delivered to 31 children with a recurrent brain ependymoma after a standard treatment. Each child was followed up with clinical and MRI examinations. We evaluated overall survival, local recurrence free-survival and short term toxicity according to CTCAE 4.0 scale. RESULTS: With a median follow-up of 37 months (range, 0 to 107), median local recurrence free-survival was 31 months (range, 2 to 63) and median overall survival was 34 months (range, 3 to 63). It was significantly higher in patients who underwent surgery first, compared with re-irradiation only. Cumulated dosimetric data were available for 22 patients. On average, maximal BED to brain stem was 106,2 Gyα/ß3 (±35,4) for infratentorial re-irradiation. No acute toxicity grade >2 was reported and 1 case of brain radionecrosis treated successfully with steroids was reported after radiosurgery. CONCLUSION: Local recurrence of brain ependymoma can be treated with full-dose re-irradiation, which can be hypofractionated with an acceptable short term toxicity in spite of high total doses delivered to OARs, especially brain stem.


Assuntos
Neoplasias Encefálicas/radioterapia , Ependimoma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adolescente , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Radiação Cranioespinal/efeitos adversos , Radiação Cranioespinal/métodos , Ependimoma/cirurgia , Feminino , Humanos , Lactente , Masculino , Intervalo Livre de Progressão , Lesões por Radiação/etiologia , Radiocirurgia , Radioterapia Adjuvante , Reirradiação/efeitos adversos , Reirradiação/métodos , Estudos Retrospectivos , Taxa de Sobrevida
7.
Lancet Oncol ; 20(3): e155-e166, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842059

RESUMO

Inhomogeneities in radiotherapy dose distributions covering the vertebrae in children can produce long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia. In the published literature, many often interrelated variables have been reported to affect the extent of potential radiotherapy damage to the spine. Articles published in the 2D and 3D radiotherapy era instructed radiation oncologists to avoid dose inhomogeneity over growing vertebrae. However, in the present era of highly conformal radiotherapy, steep dose gradients over at-risk structures can be generated and thus less harm is caused to patients. In this report, paediatric radiation oncologists from leading centres in 11 European countries have produced recommendations on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimise the risk of long-term spinal problems. Based on available information, it is advised that homogeneous vertebral radiotherapy doses should be delivered in children who have not yet finished the pubertal growth spurt. If dose fall-off within vertebrae cannot be avoided, acceptable dose gradients for different age groups are detailed here. Vertebral delineation should include all primary ossification centres and growth plates, and therefore include at least the vertebral body and arch. For partial spinal radiotherapy, the number of irradiated vertebrae should be restricted as much as achievable, particularly at the thoracic level in young children (<6 years old). There is a need for multicentre research on vertebral radiotherapy dose distributions for children, but until more valid data become available, these recommendations can provide a basis for daily practice for radiation oncologists who have patients that require vertebral radiotherapy.

9.
Eur J Heart Fail ; 21(4): 509-518, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30592114

RESUMO

BACKGROUND: Paediatric cancer survivors have a high risk of developing cardiac diseases, and the most frequent cardiac disease is heart failure (HF). The radiation dose-volume effects in the heart and cardiac substructures have not been explored in childhood cancer survivors (CCS). Therefore, the role of irradiated heart volume in the occurrence of HF among this population remains unclear. The aims of this study were to determine the doses and irradiated volumes of the heart and left ventricle (LV) related to the risk of HF in CCS and to investigate the impact of anthracycline exposure on this risk. METHODS AND RESULTS: A case-control study nested in the French Childhood Cancer Survivors Study cohort. The mean heart and left ventricular doses and volumes indicators were estimated by reconstruction of individual treatments. A total of 239 HF cases and 1042 matched controls were included. The median age of HF diagnosis was 25.1 years. The median volume of the heart that received ≥ 30 Gy was 61.1% for cases and 16.9% for controls. In patients who did not receive anthracycline, the risk of HF was increased 3.6-fold when less than 10% of the LV received ≥ 30 Gy when compared to patients who were not exposed to any cardiac radiation and anthracycline. CONCLUSIONS: Small irradiated volumes of the heart or LV were significantly associated with HF risk. To the author's knowledge, this is the first study to report a dose-response relationship based on dose-volume indicators in CCS, which can be translated efficiently into current clinical practice.

10.
J Surg Educ ; 76(3): 604-606, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30563783

RESUMO

OBJECTIVE: We describe an innovative medical student surgery interest group and its influence on mentorship and career exploration. DESIGN: SCRUBS, created to promote interest in academic surgery, is student-led, with continual surgical faculty and resident involvement. Its 3-component programming focuses on clinical skills, research, and mentorship opportunities for medical students to get involved in academic surgery early in medical education. SETTING: The University of Michigan Medical School, Ann Arbor, MI. PARTICIPANTS: First through fourth year medical students, surgery residents, and attending surgeons. RESULTS: SCRUBS is a multifaceted student organization providing longitudinal exposure to various aspects of surgery and academic medicine. The group grew annually from 2010 to 2014, with students and faculty expressing positive feedback. Over the time period reviewed, we had a greater percentage of students applying into surgical specialties compared with the national average (16.8 vs 12% in 2014). The group supported and facilitated mentorship, clinical skills development, and research opportunities for interested students. CONCLUSIONS: This innovative surgery interest group has been well received by students and surgeons, and our institution has seen above-average interest in surgical careers. Early, preclinical mentorship and exposure provided by SCRUBS may contribute to this higher surgical interest.

11.
Cancer Med ; 7(12): 5879-5888, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30449071

RESUMO

BACKGROUND, METHODS: To describe the characteristics, treatments (systemic/local), and outcome (oncological/functional) of French patients with head and neck Ewing's sarcomas (HNES) registered in the Euro-Ewing 99 (EE99) database. Specific patient-level data were reviewed retrospective. RESULTS: Forty-seven HNES patients in the EE99 database had a median age of 11 years, 89% had bone tumors (skull 55%, mandible 21%, maxilla 11%), 89% had small tumors (<200 mL), and they were rarely metastatic (9%). Local treatment was surgery radiotherapy (55%), exclusively surgery (28%), or radiotherapy (17%). Metastatic relapses occurred in five patients with high relapse risk factors (metastasis at diagnosis, poor histological response, large tumors). Local progression/relapses (LR) after exclusive radiotherapy occurred in three patients with persistent extra-osseous residue and in four patients considered R0 margins (postchemotherapy surgery, without postoperative radiotherapy [PORT]), reclassified by pathological review as R1a. Pathological review reclassified 72% of R0 margins: 11/18 to R1a and 2/18 to R2. Five patients had confirmed R0 margins after postchemotherapy surgery without PORT and had no LR Eight patients had R2 margins (initial surgery without previous chemotherapy, with PORT) and had no LR With a median follow-up of 9.3 years, the 3-year LR rate, EFS, and OS were 84.8%, 78.6%, and 89.3%, respectively. Among the 5-year survivors, 88% had long-term sequelae. CONCLUSION: To optimize HNES management, patients should be treated from diagnosis in expert centers with multidisciplinary committees to discuss treatment strategy (type of surgery, need for PORT) and validate surgical margins.


Assuntos
Neoplasias Ósseas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Margens de Excisão , Sarcoma de Ewing/terapia , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Masculino , Sarcoma de Ewing/patologia , Adulto Jovem
12.
J Neurosurg Pediatr ; 22(6): 678-683, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30192215

RESUMO

OBJECTIVEDiffuse intrinsic pontine glioma (DIPG) is a highly aggressive and lethal brainstem tumor in children. In the 1980s, routine biopsy at presentation was abandoned since it was claimed "unnecessary" for diagnosis. In the last decade, however, several groups have reincorporated this procedure as standard of care or in the context of clinical trials. Expert neurosurgical teams report no mortality and acceptable morbidity, and no relevant complications have been previously described. The aim of this study was to review needle tract dissemination as a potential complication in DIPG.METHODSThe authors retrospectively analyzed the incidence of dissemination through surgical tracts in DIPG patients who underwent biopsy procedures at diagnosis in 3 dedicated centers. Clinical records and images as well as radiation dosimetry from diagnosis to relapse were reviewed.RESULTSFour patients (2 boys and 2 girls, age range 6-12 years) had surgical tract dissemination: in 3 cases in the needle tract and in 1 case in the Ommaya catheter tract. The median time from biopsy to identification of dissemination was 5 months (range 4-6 months). The median overall survival was 11 months (range 7-12 months). Disseminated lesions were in the marginal radiotherapy field (n = 2), out of the field (n = 1), and in the radiotherapy field (n = 1).CONCLUSIONSAlthough surgical tract dissemination in DIPG is a rare complication (associated with 2.4% of procedures in this study), it should be mentioned to patients and family when procedures involving a surgical tract are proposed. The inclusion of the needle tract in the radiotherapy field may have only limited benefit. Future studies are warranted to explore the benefit of larger radiotherapy fields in patients with DIPG.


Assuntos
Biópsia/efeitos adversos , Neoplasias do Tronco Encefálico/patologia , Glioma/patologia , Invasividade Neoplásica/patologia , Ponte/patologia , Criança , Feminino , Humanos , Masculino
13.
Int J Radiat Oncol Biol Phys ; 102(1): 166-173, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30102193

RESUMO

PURPOSE: The objective of this study was to analyze survival and prognostic factors for children, adolescents, and young adults treated with postoperative radiation therapy (RT) for intracranial ependymoma. METHODS AND MATERIALS: Between 2000 and 2013, 202 patients aged ≤25 years were treated in the 13 main French pediatric RT reference centers. Their medical records were reviewed for information, treatments received, and survival rates. All children had received postoperative RT- conformal, intensity modulated, or proton beam. In 2009, the prescribed standard dose in France rose from 54 Gy to 59.4 Gy. RESULTS: Median follow-up was 53.8 months (95% confidence interval [CI] 47-63.5). Median age at RT was 5 years (range 1-22), and 32% of the children treated were aged <3 years. Regarding treatment, 85.6% of patients underwent gross total resection, 62% of patients received conformal RT (vs 29% for intensity modulated RT and 8% for proton beam RT), 62.4% of patients received a dose >54 Gy, and 71% received chemotherapy. Of the 84 relapses, 75% were local. The cumulative incidence of local relapse was 24.4% (95% CI 18.2-31.2) at 3 years and 31.3% (95% CI 24-38.9) at 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 50.4% (95% CI 42.2-58) and 71.4% (95% CI 63.1-78.2). Tumor grade was the only prognostic factor for local relapse and DFS. Tumor grade, age, and extent of resection were independent prognostic factors for overall survival. CONCLUSIONS: We confirmed several clinical and tumoral prognostic factors in a large French multicenter study. DFS for intracranial ependymoma remains low, and new biological and imaging markers are needed to distinguish among different subtypes, adapt treatments, and improve survival.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Ependimoma/diagnóstico , Ependimoma/radioterapia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico , Dosagem Radioterapêutica , Adulto Jovem
14.
Bull Cancer ; 105(9): 830-838, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-30126610

RESUMO

Sarcomas are a common type of tumor within the pediatric population. The utilization of proton therapy as a primary attribute the ability to spare adjacent healthy tissue, therefore, proton therapy has become a preferential indication in pediatrics compared to other photon irradiation modalities. Proton therapy is also a proven and historically validated irradiation technique in the treatment of chondrosarcomas and chordomas of the skull base and spine. Additionally, proton therapy can potentially limit irradiated healthy tissue volumes in adults and limit the risk of acute and late toxicities. The evaluation of the effectiveness of proton therapy in sarcomas is underway in many clinical situations in prospective trials, some of which are randomized.


Assuntos
Neoplasias Ósseas/radioterapia , Terapia com Prótons/métodos , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Criança , Condrossarcoma/radioterapia , Cordoma/radioterapia , Humanos , Terapia com Prótons/efeitos adversos , Tolerância a Radiação , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Coluna Vertebral/radioterapia
15.
Radiother Oncol ; 129(3): 520-526, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30021697

RESUMO

BACKGROUND AND PURPOSE: Skull-base chondrosarcoma (ChSa) is a rare bone tumor and the outcome of patients with this malignancy has been documented only in a limited number of series with a restricted number of patients. OBJECTIVE: This study was conducted to assess the outcome and prognostic factors of a large cohort of ChSa patients treated with radiotherapy in two proton therapy centers. MATERIALS AND METHODS: From 1996 to 2015, 251 (male, 43.4%) patients (mean age, 42.0 ±â€¯16.2 years) were treated with protons with (n = 135; 53.8%) or without photons (n = 116; 46.2%). Median delivered dose was 70.2 GyRBE. Failure-free survival (FFS), overall survival (OS) and CTCAE grade ≥3 toxicity free survival (TFS) were calculated using the Kaplan-Meier method. RESULTS: After a median follow-up of 88.0 months for surviving patients, local and distant failures were observed in 12 (4.8%) and 4 (1.6%) patients, respectively. Late failures >6 years were observed in 4 (33.3%) patients. The estimated 7-year FFS was 93.1%. Twenty-five (10%) patients died. The estimated 7-year OS was 93.6%. Tumor volume (p = 0.006) and optic pathway compression (p = 0.027) were significantly associated with the risk of treatment failure on univariate analysis. Treatment failure was significantly associated with a higher risk of death (hazard ratio = 126). The estimated 7-year TFS was 84.2%. CONCLUSIONS: The outcome of skull-base ChSa patients treated with high-dose protons with or without photons is excellent, particularly for patients with small tumors with no optic pathway compression. Treatment failure was however associated with a significantly increased risk of death.


Assuntos
Condrossarcoma/radioterapia , Terapia com Prótons/métodos , Neoplasias da Base do Crânio/radioterapia , Adulto , Condrossarcoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Base do Crânio/mortalidade , Falha de Tratamento
16.
Radiother Oncol ; 127(1): 103-107, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29500084

RESUMO

BACKGROUND AND PURPOSE: Ependymoma is the third most common brain tumor in children. Radiation therapy (RT) is systematically administered after maximum surgical resection, utilizing recent advances in radiation delivery. Imaging can make a significant contribution to improving treatment outcome. This prompted us to look for significant preoperative and postoperative imaging markers for survival. MATERIAL AND METHODS: We undertook a national retrospective review of 121 patients who had undergone resection followed by RT. Preoperative tumor volumes on T1 and FLAIR images were delineated, together with postoperative hyperintense volumes on FLAIR images. Overall survival (OS) and disease-free survival (DFS) analyses included clinical data and volumes extracted from images. RESULTS: After a median follow-up of 38.5 months, 80.2% of patients were alive, but 39.7% had experienced at least one event. Statistically significant differences between patients with and without postoperative FLAIR abnormalities were found for both DFS (71.9% vs. 40.3%; p = 0.006) and OS (93.7% vs. 72.4%; p = 0.023) in the univariate analyses, and for OS (p = 0.049) in the multivariate analyses. CONCLUSIONS: Postoperative FLAIR hyperintensities are a negative prognostic factor for intracranial ependymoma and may be a surrogate for residual disease. They could therefore prove helpful in patients' surgical and radiotherapeutic management.


Assuntos
Neoplasias Encefálicas/radioterapia , Ependimoma/radioterapia , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Ependimoma/diagnóstico por imagem , Ependimoma/patologia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Análise Multivariada , Neoplasia Residual/diagnóstico por imagem , Período Pós-Operatório , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
17.
Bull Cancer ; 105(5): 523-536, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29576221

RESUMO

Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma that typically affects pediatric and young adult patients with a median age in the general and in the pediatric population of 24.6 years (range 4-58 years) and 15.0 years (range 0-21 years) respectively, with a strong male predominance. This tumor is characterized by a specific t(11;22)(p13;q12) that results in fusion of EWS and WT1 genes which can be demonstrated by RT-PCR or by FISH. DSRCT most frequently presents as an intra-abdominal primary mass associated with peritoneal seeding and a highly aggressive pattern of spread. Generally, all tumors showed the typical histologic findings of variably sized clusters of poly-phenotypic small, round, or spindled cells lying in a desmoplastic stroma. Treatment of this malignancy remains a challenge. The combination of polychemotherapy regimens and aggressive surgery followed by whole abdomen radiation therapy represents nowadays a classical protocol for DSRCT. The survival rate of DSRCT patients is still disappointing around 20 %. However, the survival of patients who had complete resection of the tumor appears better. Hopes are turning to targeted therapeutics against this simple genomic sarcoma. Authors summarize medical knowledge of this rare tumor.


Assuntos
Tumor Desmoplásico de Pequenas Células Redondas , Doenças Raras , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 22 , Tumor Desmoplásico de Pequenas Células Redondas/genética , Tumor Desmoplásico de Pequenas Células Redondas/mortalidade , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Tumor Desmoplásico de Pequenas Células Redondas/terapia , Feminino , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Prognóstico , Doenças Raras/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Doenças Raras/terapia , Translocação Genética , Adulto Jovem
18.
Int J Radiat Oncol Biol Phys ; 100(4): 980-986, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29485078

RESUMO

PURPOSE: To identify the incidence of patients with perihippocampal metastases to assess the risk of brain relapse when sparing the hippocampal area. Medulloblastoma (MB) represents 20% of pediatric brain tumors. For high-risk MB patients, the 3- to 5-year event-free survival rate has recently improved from 50% to >76%. Many survivors, however, experience neurocognitive side effects. Several retrospective studies of patients receiving whole brain irradiation (WBI) have suggested a relationship between the radiation dose to the hippocampus and neurocognitive decline. The hippocampal avoidance-WBI (HA-WBI) approach could partially reduce neurocognitive impairment in children treated for high-risk MB. METHODS AND MATERIALS: From 2008 to 2011, 51 patients with high-risk MB were treated according to the French trial primitive neuroectodermal tumor HR+5. Hippocampal contouring was manually generated on 3-dimensional magnetic resonance images according to the Radiation Therapy Oncology Group 0933 atlas. The distribution of metastases was assessed relative to the hippocampus: 0 to 5 mm for the first perihippocampal area and 5 to 15 mm for the rest of the perihippocampal area. RESULTS: The median patient age was 8.79 years (33% female). After a follow-up of 2.4 years, 43 patients were alive; 28 had had brain metastasis at diagnosis and 2 at relapse, with 16% in the first perihippocampal area and 43% in the rest of the perihippocampal area. Of the 18 patients without brain metastases at diagnosis, including M1 patients, none developed secondary lesions within the first or the rest of the perihippocampal area, after receiving 36 Gy. No clinical or biological factor was significantly associated with the development of perihippocampal metastases. CONCLUSIONS: Our results suggest the HA-WBI strategy should be evaluated for the subgroup of high-risk MB patients without metastatic disease.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal/métodos , Hipocampo/efeitos da radiação , Meduloblastoma/radioterapia , Meduloblastoma/secundário , Transtornos Neurocognitivos/prevenção & controle , Tratamentos com Preservação do Órgão/métodos , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Cerebelares/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Meduloblastoma/diagnóstico por imagem , Transtornos Neurocognitivos/etiologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida/tendências
19.
J Neuropathol Exp Neurol ; 77(3): 207-215, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361006

RESUMO

Pediatric chordomas are rare malignant neoplasms, and few data are available for optimizing therapeutic strategies and outcome. This study aimed at evaluating how best to manage them and to identify prognostic factors. This multicentric retrospective study included 40 children diagnosed with chordomas between 1966 and 2012. Clinical, radiological, and histopathological data, treatment modalities, and outcomes were reviewed. The median age was 12 years old. Most chordomas were histologically classical forms (45.5%) and were mostly located at the skull base (72.5%). The overall survival (OS) was 66.6% and 58.6%, and progression-free survival (PFS) was 55.7% and 52% at 5 and 10 years, respectively. Total resection was correlated with a better outcome (p = 0.04 for OS and PFS, log-rank). A histopathological/immunohistochemical grading system recently crafted for adults was applied. In a multivariate analysis, it significantly correlated with outcome (PFS and OS, p = 0.004), and the loss of BAF47 immunoexpression appeared to be a significant independent prognostic factor (PFS, p = 0.033). We also identified clinical and histopathological parameters that correlated with prognosis. A new grading system combined with the quality of surgical resection could help classify patients to postpone radiotherapy in case of low risk. Targeted therapy and reirradiation at recurrence may be considered as potential therapeutic strategies.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Cordoma/diagnóstico , Cordoma/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Proteínas Fetais/metabolismo , Seguimentos , Humanos , Antígeno Ki-67/metabolismo , Masculino , Prognóstico , Radioterapia , Estudos Retrospectivos , Proteína SMARCB1/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas com Domínio T/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Radiother Oncol ; 128(2): 198-202, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29310903

RESUMO

BACKGROUND AND PURPOSE: To evaluate clinical results and safety of a dose adaptive protocol based on tumor volume coverage and critical structure constraints, for the treatment of skull base chordomas. MATERIAL AND METHODS: Between May 2006 and October 2012, 106 patients with skull base chordoma were treated by combined photon and proton irradiation. Prescribed dose levels were 68.4, 70.2, 72 and 73.8 Gy(RBE) in once daily fractionation of 1.8 Gy(RBE). Dose level and dosimetric constraints to organs at risk depended on postoperative residual Gross Tumor Volume (GTV) coverage. Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method. RESULTS: With a median follow-up of 61 months, the 2-year, 4-year, and 5-year LC rates were 88.6%, 78.3%, and 75.1%, respectively. GTV > 25 mL (p = 0.034, HR = 2.22; 95%CI 1.06-4.62) was an independent unfavorable prognostic factor of LC. The 2-year, 4-year, and 5-year OS rates were 99%, 90.2%, and 88.3%, respectively. Grade 3-5 late toxicity was observed in 7 patients, resulting in 93% 5-year freedom from high-grade toxicity. CONCLUSIONS: This study suggests that the probability of LC of skull base chordomas depends on postoperative GTV. The dose adaptive protocol achieves acceptable local control. Future studies should investigate whether further dose escalation to doses in excess of 74 Gy(RBE) would achieve better results.


Assuntos
Cordoma/radioterapia , Terapia com Prótons/métodos , Neoplasias da Base do Crânio/radioterapia , Adolescente , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
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