ABSTRACT
AIMS: There is a crucial need for pharmacokinetic (PK) data on oral vinorelbine (VNR) in the paediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). METHODS: A multicentre, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumours, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. RESULTS: PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t1/2 ) and their between-subject variability (CV%) at 60 mg m-2 dose level, were 472 L h-1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (P = .004). Lower area under the concentration-time curve (AUC) levels were observed among children in comparison to adults. CONCLUSION: Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among paediatric patients.
Subject(s)
Glioma , Neoplasm Recurrence, Local , Adolescent , Child , Glioma/drug therapy , Half-Life , Humans , Infusions, Intravenous , Neoplasm Recurrence, Local/drug therapy , VinorelbineABSTRACT
INTRODUCTION: Medulloblastoma is the most common malignant brain tumor in children, but accounts for only 1% of brain cancers in adults. For standard-risk pediatric medulloblastoma, current therapy includes craniospinal irradiation (CSI) at reduced doses (23.4 Gy) associated with chemotherapy. Whereas most same-stage adult patients are still given CSI at 36 Gy, with or without chemotherapy, we report here on our use of reduced-dose CSI associated with chemotherapy for older patients. METHODS: We gathered non-metastatic patients over 18 years old (median age 28 years, range 18-48) with minimal or no residual disease after surgery, no negative histological subtypes, treated between 1996-2018 at the Centre Léon Bérard (Lyon) and the INT (Milano). A series of 54 children with similar tumors treated in Milano was used for comparison. RESULTS: Forty-four adults were considered (median follow-up 101 months): 36 had 23.4 Gy of CSI, and 8 had 30.6 Gy, plus a boost to the posterior fossa/tumor bed; 43 had chemotherapy as all 54 children, who had a median 83-month follow-up. The PFS and OS were 82.2 ± 6.1% and 89 ± 5.2% at 5 years, and 78.5 ± 6.9% and 75.2 ± 7.8% at ten, not significantly different from those of the children. CSI doses higher than 23.4 Gy did not influence PFS. Female adult patients tended to have a better outcome than males. CONCLUSION: The results obtained in our combined series are comparable with, or even better than those obtained after high CSI doses, underscoring the need to reconsider this treatment in adults.
Subject(s)
Cerebellar Neoplasms/radiotherapy , Craniospinal Irradiation/mortality , Medulloblastoma/radiotherapy , Adolescent , Adult , Cerebellar Neoplasms/pathology , Dose-Response Relationship, Radiation , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Medulloblastoma/pathology , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
AIM: To assess objective response after two cycles of temozolomide and topotecan (TOTEM) in children with refractory or relapsed miscellaneous extracranial solid and central nervous system (CNS) tumors, including medulloblastoma and primitive neuroectodermal tumors (PNET). PROCEDURE: Multicenter, nonrandomized, phase 2 basket trial including children with solid tumors, completed by a one-stage design confirmatory cohort for medulloblastoma, and an exploratory cohort for PNET. Main eligibility criteria were refractory/relapsed measurable disease and no more than two prior treatment lines. Temozolomide was administered orally at 150 mg/m2 /day followed by topotecan at 0.75 mg/m2 /day intravenously for five consecutive days every 28 days. Tumor response was assessed every two cycles according to WHO criteria and reviewed independently. RESULTS: Thirty-two patients were enrolled and treated in the miscellaneous solid tumor and 33 in the CNS strata; 20 patients with medulloblastoma and six with PNET were included in the expansion cohorts. The median age at inclusion was 10.0 years (range, 0.9-20.9). In the basket cohorts, confirmed complete and partial responses were observed in one glioma, four medulloblastoma, and one PNET, leading to the extension. The overall objective response rate (ORR) in medulloblastoma was 28% (95% CI, 12.7-47.2) with 1/29 complete and 7/29 partial responses, those for PNET 10% (95% CI, 0.3-44.5). Post hoc Bayesian analysis estimates that the true ORR in medulloblastoma is probably between 20% and 30% and below 20% in PNET. The most common treatment-related toxicities of the combination therapy were hematologic. CONCLUSIONS: Temozolomide-topotecan results in significant ORR in children with recurrent and refractory medulloblastoma with a favorable toxicity profile.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Medulloblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neuroectodermal Tumors, Primitive/drug therapy , Salvage Therapy , Adolescent , Adult , Bayes Theorem , Central Nervous System Neoplasms/pathology , Cerebellar Neoplasms/drug therapy , Cerebellar Neoplasms/pathology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Medulloblastoma/pathology , Neoplasm Recurrence, Local/pathology , Neuroectodermal Tumors, Primitive/pathology , Prognosis , Survival Rate , Temozolomide/administration & dosage , Topotecan/administration & dosage , Young AdultABSTRACT
Objective: Childhood brain tumors (BTs) and their treatment often negatively affect development of executive functions. Previous studies have reported executive functions deficits, particularly through questionnaires of daily life. This study aimed to assess executive functioning in everyday life following pediatric BT, in a larger and more histologically diverse sample than previously, and to study clinical and demographic factors influencing outcome.Methods: Assessment of executive functioning using parent ratings of the Behavior Rating Inventory of Executive Function (BRIEF), in a large sample of children treated for various BT (n = 153). Clinical and demographic factors were: age at diagnostic, age at assessment, parental education level, radiation therapy.Results: Significant difficulties were found in the 3 composite indices and in the majority of the BRIEF subscales. The highest level of difficulties was observed in the Working Memory subscale. Older age at assessment and younger age at diagnosis were significantly associated with higher levels of parent-reported difficulties, particularly for metacognition.Conclusions: Parents of children treated for BT report widespread and persistent deficits in executive functions that negatively affect their everyday functioning. Including analysis of all clinical scales and composite indices allows a more comprehensive approach and enables to specify the patients' executive profile.
Subject(s)
Brain Neoplasms , Metacognition , Adolescent , Aged , Brain Neoplasms/radiotherapy , Child , Executive Function , Humans , Memory, Short-Term , Neuropsychological Tests , Parents , Surveys and QuestionnairesABSTRACT
The European Association of Neuro-Oncology (EANO) and EUropean RAre CANcer (EURACAN) guideline provides recommendations for the diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. The guideline is based on the 2016 WHO classification of tumours of the CNS and on scientific developments published since 1980. It aims to provide direction for diagnostic and management decisions, and for limiting unnecessary treatments and cost. In view of the scarcity of data in adults with medulloblastoma, we base our recommendations on adult data when possible, but also include recommendations derived from paediatric data if justified. Our recommendations are a resource for professionals involved in the management of post-pubertal and adult patients with medulloblastoma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
Subject(s)
Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/therapy , Medulloblastoma/diagnosis , Medulloblastoma/therapy , Practice Guidelines as Topic/standards , Puberty , Adolescent , Adult , Europe , Follow-Up Studies , HumansABSTRACT
DNMT3A codes for a DNA methyl transferase enzyme that plays a central role embryogenesis. Somatic mutations in this gene have been associated with tumorigenesis and are associated with a number of cancers. The recently described Tatton-Brown-Rahman syndrome (TBRS) is due to heterozygous germline mutations in the DNMT3A gene. So far, only one case of hematological malignancy associated with TBRS have been reported. Here, we describe the first case presenting with TBRS and medulloblastoma. We also discuss the associations between mutations in DNMT3A found in TBRS, AML, and medulloblastoma.
Subject(s)
Cerebellar Neoplasms/genetics , Intellectual Disability/genetics , Medulloblastoma/genetics , Adolescent , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methyltransferase 3A , Female , Humans , Mutation , SyndromeABSTRACT
BACKGROUND: Volasertib induces mitotic arrest and apoptosis by targeting Polo-like kinases. In this phase I dose-escalation study, the maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of volasertib were determined in pediatric patients. METHODS: Patients aged 2 to <18 years with relapsed/refractory acute leukemia/advanced solid tumors (ST) without available effective treatments were enrolled-cohort C1 (aged 2 to <12 years); cohort C2 (aged 12 to <18 years). The patients received volasertib intravenously (starting dose: 200 mg/m2 body surface area on day 1, every 14 days). The primary endpoint was the pediatric MTD for further development. RESULTS: Twenty-two patients received treatment (C1: leukemia, n = 4; ST, n = 8; C2: leukemia, n = 3; ST, n = 7). No dose-limiting toxicities (DLTs) occurred up to 300 mg/m2 volasertib in C1; two patients in C2, at 250 mg/m2 volasertib, had DLTs in cycle 1, one of which led to death; therefore, the MTD of volasertib in C2 was 200 mg/m2 . The most common grade 3/4 adverse events (all patients) were febrile neutropenia, thrombocytopenia, and neutropenia (41% each). Stable disease (SD) was the best objective response (leukemia, n = 5; ST, n = 2); the duration of SD was short in all patients, except in one with an ST. PK profiles were generally comparable across dose groups and were consistent with those in adults. CONCLUSION: The pediatric MTD/dose for further development was identified. There were no unexpected safety or PK findings; limited antitumor/antileukemic activity was demonstrated.
Subject(s)
Leukemia/drug therapy , Neoplasms/drug therapy , Pteridines/administration & dosage , Pteridines/pharmacokinetics , Adolescent , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Male , Maximum Tolerated Dose , Pteridines/adverse effectsABSTRACT
INTRODUCTION: Medulloblastoma is the most common malignant cerebral tumor during childhood, arising in the posterior fossa. Children treated for medulloblastoma often experience working memory (WM) deficits, affecting their quality of life and school performance. The aim of the present study undertaken to describe the cerebellar involvement in WM deficits observed in these children. MATERIAL AND METHODS: 23 healthy children and 11 children treated for medulloblastoma were included into study. All subjects performed a detailed neuropsychological examination, an anatomical and functional MRI. Stimuli were presented to the participants with alternating sensory modality and nature of communication in a block design during functional magnetic resonance imaging acquisitions. Non-parametric tests were used for analyzing neuropsychological and behavioral data. SPM8 and SUIT (Spatially Unbiased Atlas Template) were used for anatomical and functional MRI data analyses. RESULTS: Patients had cerebellar resections mainly located in the left posterior lobe. Patients had significantly reduced intelligence quotient, central executive and visuospatial WM. In healthy children group, fMRI showed activations for non-verbal and visuospatial WM in the left posterior cerebellar lobe. CONCLUSION: This study provides further evidence that left posterior cerebellar lobe plays a critical role in WM. Indeed, lesions of left posterior cerebellar lobe were associated with WM impairment in children treated for cerebellar medulloblastoma. Additionally, fMRI using WM tasks showed activation in the left posterior cerebellar lobe in healthy children. Taken together, these findings may help for improving treatment and rehabilitation of children referred for cerebellar tumor.
Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/psychology , Cerebellar Diseases/diagnostic imaging , Cerebellar Diseases/psychology , Magnetic Resonance Imaging/methods , Medulloblastoma/diagnostic imaging , Medulloblastoma/psychology , Memory, Short-Term , Adolescent , Brain Mapping , Brain Neoplasms/surgery , Child , Female , France , Humans , Intellectual Disability/etiology , Male , Medulloblastoma/surgery , Neuropsychological Tests , Neurosurgical Procedures , Quality of Life , Risk FactorsABSTRACT
PURPOSE OF REVIEW: Medulloblastoma is no more a unique disease. Clinical and biologic classification used so far are challenged by molecular classification(s). Following the consensus article that described four molecular groups of medulloblastoma in 2012, several articles in 2017 provided more relevant classifications that may impact on further clinical trial design. RECENT FINDINGS: Though wingless (WNT) and sonic hedgehog (SHH) are defined by the activation of their respective pathways, the age and type of activation define various subgroups with specific features and outcome. Groups 3 and 4 remain ill defined. The whole population of medulloblastoma may be divided in 12 subgroups: WNTαß, SHHαßγδ, group 3αßγ and group 4αßγ. The paediatric population may be divided in seven subgroups: WNT, SHH of infants and children, and low-risk and high-risk groups 3 and 4. SHH of infants may be divided as iSHH-I vs. iSHH-II that have different prognosis. Moreover, specific drivers of groups 3 and 4 were reported. SUMMARY: These findings have and will have direct implications on the conception of clinical trials. Low-risk groups will benefit from less toxic therapies, and high-risk groups will benefit from targeted therapies.
Subject(s)
Cerebellar Neoplasms/classification , Cerebellar Neoplasms/genetics , Medulloblastoma/classification , Medulloblastoma/genetics , Prognosis , Biomarkers , Cerebellar Neoplasms/diagnosis , Humans , Medulloblastoma/diagnosis , Predictive Value of TestsABSTRACT
LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70. MATERIALS AND METHODS: Patients aged ≥70 years with a KPS <70 and biopsy-proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130-150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks. RESULTS: The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19-27.6), and the median progression-free survival (PFS) was 15.3 weeks (95% CI, 12.9-19.3). Twenty-two (33%) patients became transiently capable of self-care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%). CONCLUSION: This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.
Subject(s)
Bevacizumab/therapeutic use , Glioblastoma/drug therapy , Temozolomide/therapeutic use , Aged , Aged, 80 and over , Bevacizumab/pharmacology , Female , Humans , Male , Temozolomide/pharmacologyABSTRACT
Adult cerebellar glioblastomas (cGBM) are rare and their characteristics remain to be fully described. We analyzed the characteristics of 17 adult patients with cGBM and compared them to a series of 103 patients presenting a supra-tentorial glioblastoma (stGBM). The mean age at GBMc diagnosis was 53.4 years (range 28-77). A history of neurofibromatosis type I was noted in 3 patients. cGBM were hemispheric in 10 patients (58.8%), only vermian in 4 patients (23.5%), and both vermian and hemispheric in 3 patients (17.7%). A H3 K27M mutation was identified in 3/14 patients, a TERT promoter mutation in 3/14 patients and a methylated MGMT promoter in 3/14 patients. None of the patients (0/14) harbored an EGFR amplification, an IDH or a BRAF mutation. Association with neurofibromatosis type I and H3K27M mutations were mutually exclusive. Compared with stGBM, cGBM occurred in younger patients (53.4 vs. 63.2, p = 0.02), were more frequently associated with neurofibromatosis type I (18 vs. 1%, p = 0.009) and with a H3 K27M mutation (21 vs. 3%, p = 0.02). They also tended to have a more frequent multifocal presentation at diagnosis (21 vs. 4.3%, p = 0.06), more frequently resulted in leptomeningeal or intra-axial metastasis (44.5 vs. 5%, p = 0.002) and were associated with a shorter median overall survival (5.9 vs. 14.2 months, p = 0.004). The present study suggests that adult cGBM differ from their supra-tentorial counterpart and constitute a heterogeneous group of IDH wild-type gliomas with at least two subgroups, one associated with H3K27M mutations and the other with neurofibromatosis type I.
Subject(s)
Cerebellar Neoplasms/epidemiology , Glioblastoma/epidemiology , Adult , Age Factors , Aged , Cerebellar Neoplasms/genetics , Female , Follow-Up Studies , Glioblastoma/genetics , Humans , Male , Middle Aged , Mutation , Neurofibromatosis 1/epidemiology , Retrospective Studies , Supratentorial Neoplasms/epidemiology , Supratentorial Neoplasms/geneticsABSTRACT
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.
Subject(s)
Central Nervous System Neoplasms/therapy , Adolescent , Central Nervous System Neoplasms/diagnosis , Child , Child, Preschool , Clinical Trials, Phase I as Topic , Disease Progression , Female , Humans , Infant , Kaplan-Meier Estimate , Male , Outcome Assessment, Health Care , Treatment OutcomeABSTRACT
PURPOSE: The current staging system of central nervous system (CNS) germ cell tumors (GCT) includes a binary classification in "localized" or "metastatic" disease based on the absence or presence of leptomeningeal dissemination. Loco-regional tumor dissemination has been barely described whereas its accurate definition might be useful in terms of prognosis and treatment, especially for radiation therapy planning. Our purpose was therefore to describe MR patterns and prevalence of loco-regional extensions of these tumors. METHODS: One hundred consecutive patients (median age 16.3 years, range 7-41 years, sex ratio 7:1) with a histologically or biologically proven CNS GCT were retrospectively included. Brain and spinal MRI at diagnosis were reviewed by two neuroradiologists focusing on MR patterns of primaries and loco-regional extensions. When available, follow-up MR exams were analyzed. RESULTS: Pure germinoma represented 84/100 cases. Primaries were unifocal pineal (n = 49/100), bifocal pineal and supra-sellar (n = 27/100), isolated supra-sellar (n = 21/100), isolated basal ganglia (n = 2/100) or trifocal pineal, supra-sellar, and basal ganglia (n = 1/100). Metastatic disease occurred in 6/100 patients (depicted by MRI in two and CSF cytology in four). Loco-regional extensions were observed in all patients and classified as follows: third ventricle (n = 88/100), thalamus (n = 47/100), midbrain (n = 42/100), distant sub-ependymal areas (n = 19/100), optic pathways (n = 19/100), lateral ventricles (n = 7/100), cavernous sinus (n = 6/100), corpus callosum (n = 4/100), and fourth ventricle (n = 3/100). CONCLUSION: CNS GCT present with specific loco-regional extensions at diagnosis. Improving their recognition will be helpful to further understand their prognostic value and potentially to optimize the treatment.
Subject(s)
Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/pathology , Magnetic Resonance Imaging/methods , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/pathology , Adolescent , Adult , Child , Contrast Media , Female , Humans , Image Interpretation, Computer-Assisted , Male , Neoplasm Invasiveness , Neoplasm Staging , Retrospective StudiesABSTRACT
Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth.
Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/therapy , Ependymoma/metabolism , Ependymoma/therapy , Animals , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Consensus , Disease Management , Ependymoma/genetics , Ependymoma/pathology , Humans , Neoplasm StagingABSTRACT
OBJECTIVE: Patients with brain tumors often report having visual complaints. This may be due to increased intracranial pressure, compression/invasion of the optic pathway or diplopia. We assessed the incidence and the etiology of visual symptoms in patients with intracranial germinoma tumors (ICGTs). METHODS AND MATERIALS: We performed a blinded retrospective review of the clinical charts and the initial magnetic resonance imaging (MRI) of 28 patients with ICGT. Thirteen tumors were pineal, five suprasellar, seven bifocal, and further three involved either the optic nerve, the corpus callosum, or the brainstem. RESULTS: Twelve patients reported visual disturbances, seven of whom mainly experienced a decrease in vision. Two of those were initially managed as "retrobulbar neuritis" when endocrinologic symptoms prompted assessment by MRI. Involvement of the optic pathway was underestimated, and both relapsed. Field deficits were definitive sequelae, whereas visual acuity was sometimes regressive in the absence of optic atrophy. CONCLUSIONS: Compression or invasion of the optic pathway by germinomas is not a rare occurrence, and this possibility should not be overlooked when thickening or contrast enhancement is detected. Radiotherapy fields should be extended accordingly.
Subject(s)
Brain Neoplasms , Diplopia , Germinoma , Magnetic Resonance Imaging , Nerve Compression Syndromes , Optic Nerve Diseases , Adolescent , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/epidemiology , Brain Neoplasms/physiopathology , Child , Diplopia/diagnostic imaging , Diplopia/epidemiology , Diplopia/physiopathology , Female , Germinoma/diagnostic imaging , Germinoma/epidemiology , Germinoma/physiopathology , Humans , Intracranial Pressure , Male , Nerve Compression Syndromes/diagnostic imaging , Nerve Compression Syndromes/epidemiology , Nerve Compression Syndromes/physiopathology , Optic Nerve/diagnostic imaging , Optic Nerve/physiopathology , Optic Nerve Diseases/diagnostic imaging , Optic Nerve Diseases/epidemiology , Optic Nerve Diseases/physiopathology , Retrospective StudiesABSTRACT
This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.
Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Glioblastoma/diagnosis , Glioblastoma/therapy , Glioma/diagnosis , Glioma/therapy , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Combined Modality Therapy , Europe , Evidence-Based Medicine , Female , Glioblastoma/mortality , Glioma/mortality , Humans , Male , Middle Aged , Prognosis , Risk Assessment , Societies, Medical , Survival AnalysisABSTRACT
PURPOSE: Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment. METHODS: This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment. RESULTS: At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5-23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6-46.8%) and 32% (95%CI: 12.9-52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT. CONCLUSION: In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Neoplasms, Germ Cell and Embryonal/drug therapy , Salvage Therapy , Adolescent , Adult , Bleomycin/administration & dosage , Child , Cisplatin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Ifosfamide/administration & dosage , Infant , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Prospective Studies , Survival Rate , Testicular Neoplasms , Vinblastine/administration & dosage , Young AdultABSTRACT
We studied academic and employment outcomes in 59 subjects who underwent allogeneic hematopoietic stem cell transplantation (a-HSCT) with fractionated total body irradiation (fTBI) for childhood leukemia, comparing them with, first, the general French population and, second, findings in 19 who underwent a-HSCT with chemotherapy conditioning. We observed an average academic delay of 0.98 years among the 59 subjects by Year 10 of secondary school (French class Troisième), which was higher than the 0.34-year delay in the normal population (P < .001) but not significantly higher than the delay of 0.68 years in our cohort of 19 subjects who underwent a-HSCT with chemotherapy. The delay was dependent on age at leukemia diagnosis, but not at fTBI. This delay increased to 1.32 years by the final year of secondary school (Year 13, Terminale) for our 59 subjects versus 0.51 years in the normal population (P = .0002), but did not differ significantly from the 1.08-year delay observed in our cohort of 19 subjects. The number of students who received their secondary school diploma (Baccalaureate) was similar to the expected rate in the general French population for girls (observed/expected = 1.02) but significantly decreased for boys (O/E = 0.48; CI: 95%[0.3-0.7]). Compared with 13.8% of the general population, 15.3% of the cancer survivors received no diploma (P = NS). Reported job distribution did not differ significantly between our cohort of childhood cancer survivors and the general population except that more female survivors were employed in intermediate-level professional positions. Academic difficulties after fTBI are common and their early identification will facilitate educational and professional achievement.
Subject(s)
Employment/statistics & numerical data , Hematopoietic Stem Cell Transplantation/adverse effects , Learning Disabilities/etiology , Leukemia/therapy , Transplantation Conditioning , Whole-Body Irradiation/adverse effects , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Infant , Learning Disabilities/diagnosis , Male , Myelodysplastic Syndromes/therapy , Prognosis , Survival Rate , Survivors , Transplantation, Homologous , Young AdultABSTRACT
Background: SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. Methods: CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. Results: 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Conclusion: Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.