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Combined Intraarterial Carboplatin, Intraarterial Etoposide Phosphate, and IV Cytoxan Chemotherapy for Progressive Optic-Hypothalamic Gliomas in Young Children
Abstract
Optic pathway and/or hypothalamic astrocytomas in children are often quiescent, but in some cases, more aggressive tumors may cause progressive visual, endocrine, and neurologic deterioration. The initial treatment of these gliomas includes surgery and IV chemotherapy. Radiotherapy is not recommended in young children because of its severe adverse effects on cognitive and neuroendocrine function. This report suggests a new approach using combined intraarterial and IV carboplatin-based chemotherapy for patients for whom first line treatment has already failed.
Six children (mean age, 57 months) with the diagnosis of optic pathway hypothalamic gliomas, who had tumor progression after surgery and underwent IV chemotherapy, were treated monthly with intraarterially administered carboplatin, intraarterially administered etoposide phosphate, and IV administered Cytoxan. Four of the children had histologically verified pilocytic astrocytomas, and in two cases, diagnosis was made on the basis of clinical findings. Administration of the intraarterial chemotherapy required catheter placement in both internal carotid arteries at the level of C2-C3 and into one of the vertebral arteries at the level of C6-C7, with the patient under general anesthesia.
Four of six patients had partial radiographic response, one had stable disease, and one had progressive disease after one cycle. Three patients showed clinical improvement. There were no serious complications associated with the angiographic procedures. Toxicities included bronchospasm that resolved after 3 to 4 minutes in one patient. One patient showed mild ototoxicity, and four patients needed platelet transfusion because of hematologic toxicity of drugs.
These results suggest that this modality of chemotherapy (administered after failure of systemic [ie, IV] chemotherapy), of progressive optic-hypothalamic astrocytomas in young children may be an effective treatment prior to radiotherapy.
... The most authored review article was by Aoki et al. [54], published in 1993 with 13 authors ("Supraophthalmic chemotherapy with long tapered catheter: Distribution evaluated with intraarterial and intravenous Tc-99m HMPAO" in Radiology). The authors with the most senior-authored articles overall were E.A. Neuwelt and J.A. Boockvar, who both contributed eight articles [34,36,37,51,[55][56][57][58][59][60][61][62][63][64][65][66] (Table S4). ...
... The portfolio of both these authors was predominantly focused on CL articles and clinical trials based in the USA. When considering all articles included in this study, E.A. Neuwelt was the author of most with 14 articles overall, of which he senior-authored 8 CL articles [34,51,[55][56][57][58][59][60][92][93][94]. Through the Neuro-Oncology Blood-Brain Barrier Program at OHSU, he was also involved in initiating 3 clinical trials that are currently being conducted at the OHSU Knight Cancer Institute [68,80,81]. ...
... The largest indication for intra-arterial administration was chemotherapy, with 215 of 271 articles describing its BSc or CL use. Indeed, intra-arterial chemotherapy allowed relatively high dosing while minimizing systemic toxicity [41,59,63,64]. However, articles on chemotherapeutic drugs peaked over three decades ago, possibly indicating that these therapies were lacking efficacy with intraarterial use. ...
Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.
Pediatric optic pathway gliomas (OPG) are low-grade brain tumors characterized by slow progression and invalidating visual loss. Common therapeutic strategies include surgery, radiotherapy, chemotherapy, and combinations of these modalities, but despite the different treatment strategies, no actual treatment exists to prevent or revert visual impairment. Nowadays, several reports of the literature show promising results regarding NGF eye drop instillation and improvement of visual outcome. Such results seem to be related with the NGF-linked prevention in caspase activation, which reduces retinal ganglion cell loss.
Reducing retinal ganglion cell loss results clinically in visual field improvement as well as visual electric potential and optical coherence tomography gain. Nonetheless, visual acuity fails to show significant changes.
Visual impairment represents nowadays one of the major issues in dealing with OPGs. Secondary to the interesting results offered by NGF eye drop administration, further studies are warranted to better comprehend potential treatment strategies.
Background:
OPG accounts for 3-5% of childhood central nervous system (CNS) tumors and about 2% of pediatric glial lesions.
Methods:
Article selection was performed by searching PubMed, Web of Science, and Cochrane databases.
Results:
The pooled mortality rate was 0.12 (95%CI 0.09-0.14). Due to the unrepresentative data, improved and not changed outcomes were classified as favorable outcomes and worsened as unfavorable. Meta-analyses were performed to determine the rate of clinical and radiological favorable outcomes. In terms of visual assessment, the pooled rate of a favorable outcome in chemotherapy, radiotherapy, and surgery was 0.74, 0.81, and 0.65, respectively, and the overall pooled rate of the favorable outcome was 0.75 (95%CI 0.70-0.80). In terms of radiological assessment, the rate of a favorable outcome following chemotherapy, radiotherapy, and surgery was 0.71, 0.74, and 0.67, respectively, and the overall pooled rate of the favorable outcome is 0.71 (95%CI 0.65-0.77). The subgroup analysis revealed no significant difference in the rate of clinical and radiological favorable outcomes between the different treatment modalities (p > 0.05).
Conclusion:
Our analyses showed that each therapeutic modality represents viable treatment options to achieve remission for these patients.
Chemotherapeutics play a significant role in the management of most brain tumors. First pass effect, systemic toxicity, and more importantly, the blood-brain barrier pose significant challenges to the success of chemotherapy. Over the last 80 years, different techniques of intraarterial chemotherapy delivery have been performed in many studies but failed to become standard of care. The purpose of this article is to review the history of intraarterial drug delivery and osmotic blood-brain barrier disruption, identify the challenges for clinical translation, and identify future directions for these approaches.
Background:
Progressive and/or unresectable pilocytic astrocytomas (PAs) carry a poor prognosis compared to typical PA. Early radiotherapy (RT) may have severe long-term neurocognitive side effects in this patient population. Intra-arterial (IA) chemotherapy is a viable alternative or addition to intravenous (IV) chemotherapy, which may be beneficial in avoidance of early RT.
Objective:
To evaluate the safety and efficacy of IA chemotherapy in this subset of patients.
Methods:
This is a retrospective review of medical records of PA patients who are treated with IA chemotherapy at Oregon Health & Science University from 1997 until 2019. Response to treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Progression free survival (PFS) and overall survival (OS) are also reported.
Results:
Twelve patients were identified. All patients experienced progression prior to initiation of IA chemotherapy. The most common grade 3 or 4 toxicities related to chemotherapy were thrombocytopenia (66%), neutropenia (66%), leukopenia (50%), anemia (33%), and lymphopenia (16%). Responses achieved were CR in 1, PR in 3, SD in 7, and PD in 1. Median PFS and median OS were 16.5 and 83.5 mo, respectively. A total of 112 procedures (IA injections) were performed and 250 arteries were catheterized. There were 3 minor and no major complications attributable to procedures.
Conclusion:
This study demonstrates that IA chemotherapy can be safely used in patients with unresectable or progressive PA.
Pediatric optic-hypothalamic gliomas (POHGs) have a favorable prognosis with regards to the long-term survival if compared with other pediatric tumors of the central nervous system. Indeed, in spite of the high rate of tumor progression, POHGs can reach a 10-year overall survival more than 80% in many series. The reasons of such a good survival are the indolent course and/or the favorable location (Dodge I tumors) showed by some of them, the lower trend of progression in case of associated neurofibromatosis type 1, and the good response to integrated therapies.
On the other hand, the long-term clinical outcome of affected children strongly contrasts with the survival because of the involvement of the chiasm and the hypothalamus by the tumor and the sequelae of treatment. Unilateral or bilateral severe loss of vision/visual field amputation, neurological deficits, chronic endocrine imbalance, and neuropsychological impairment actually make the quality of life of POHGs patients poor in most of the cases.
Intra-arterial (IA) chemotherapy is a form of regional delivery to brain tumors, designed to enhance the intra-tumoral concentrations of a given drug, in comparison to the intravenous route. Drugs that are likely to be benefited from IA delivery have a rapid systemic clearance and include carmustine and other nitrosoureas, cisplatin, carboplatin, etoposide, and methotrexate. Clinical studies have demonstrated activity of IA chemotherapy approaches for low- and high-grade gliomas, cerebral lymphoma, and brain metastases. However, a survival benefit for IA drug delivery, in comparison to intravenous administration, has not been proven in phase III clinical trials. The technique is limited by the potential for significant vascular and neurological toxicity, including visual loss, stroke, and leukoencephalopathy. More recent studies suggest that toxicity can be reduced by the use of carboplatin- and methotrexate-based regimens. Further clinical studies will be needed to determine the appropriate role for IA chemotherapy in the treatment of brain tumors.
Прилагането на йонизиращите лъчения при доброкачествените тумори започва още през 19-ти век.
Осъвременяването на лъчелечебната апаратура допринесе за минимизиране на риска от късни лъчеви увреждания и карциногенеза след облъчване с йонизиращи лъчения от страна на околните тъкани. Следоперативното и дефинитивно лъчелечение продължава да е актуално, приемливо и ефикасно лечение при редица доброкачествени и гранични тумори.
С въвеждането в България на линейните ускорители стана възможно прилагане на модерни лъчелечебни техники, чрез които се извършва адекватно и прецизно лъчелечение. Чрез тях се оптимизира основния принцип в лъчелечението за постигане на максимален канцерициден ефект, често комбиниран и подпомогнат от други лечебни методи като операция и химиотерапия, при едновременно минимизиране на лъчевата доза под 0,05Gy в прилежащите околни нормални тъкани и структури.
В настоящото ръководство се представя максимално съкратен материал върху разнообразните патохистологични характеристики на доброкачествените и гранични тумори, необходимата образна диагностика, възможностите за прилагане на оперативния метод, показанията за лъчелечение и отчетените в литературата късни лъчеви ефекти.
The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice.
The English literature was searched for defined search items.
Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined.
To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location.
Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins,
making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers
and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic
derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus
HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC50s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited
high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed
eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site,
at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also
shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal
antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor.
Pilocytic astrocytoma is the most common pediatric central nervous system glial neoplasm and the most common pediatric cerebellar tumor. This tumor has a noteworthy benign biologic behavior that translates into an extremely high survival rate-94% at 10 years-that is by far the best of any glial tumor. Most patients present in the first 2 decades, and clinical symptoms and signs are usually of several months duration and directly related to the specific location of the tumor. The cerebellum, optic nerve and chiasm, and hypothalamic region are the most common locations, but the tumor can also be found in the cerebral hemisphere, ventricles, and spinal cord. Surgical resection is the treatment of choice for all tumors, except for those involving the optic pathway and hypothalamic region, which may be treated with radiation therapy and chemotherapy. Cross-sectional imaging often demonstrates a classic appearance: a cystic mass with an enhancing mural nodule. Less common appearances are quite nonspecific. Surrounding vasogenic edema is rarely present, and this feature provides a valuable clue to the correct diagnosis. Accurate interpretation of imaging studies plays an essential role in directing treatment of these tumors, particularly when they arise in the optic pathway of patients with neurofibromatosis type 1. Disseminated disease and recurrence are extremely rare.
Optic chiasmatic-hypothalamic gliomas are sellar-suprasellar lesions with variable radiological features. The advocated treatment is mainly primary radiotherapy without a histological diagnosis. However, in developing countries, like India infective granulomas (tuberculomas) in the suprasellar region radiologically can mimic optic chiasmatic-hypothalamic gliomas. Hence primary radiotherapy without histological confirmation may have deleterious consequences.
The aim of the paper was to analyze the sensitivity and specificity of magnetic resonance imaging (MRI) in these lesions and to analyze the feasibility of primary radiotherapy.
The magnetic resonance imaging (MRI) characteristics of 24 patients with either histologically proven optic chiasmatic "pilocytic astrocytoma" or radiologically suspected optic chiasmatic-hypothalamic gliomas were analyzed. They were grouped into three groups on the basis of radiological features and treated with a suspected diagnosis. The final diagnosis was correlated with preoperative diagnosis, and the feasibility of managing these lesions without a histopathological confirmation is discussed.
The three radiological groups were: Group-1 solid tumors with or without microcysts in 9 patients (histology: 8 pilocystic astrocytomas and 1 tuberculoma); Group-2 mixed tumors with solid and cystic components in 9 patients (histology: 7 pilocytic astrocytomas and 2 craniopharyngiomas); Group-3 ring enhancing lesions in 6 patients (all the 6 patients initially received antituberculous treatment, in 3 patients the lesion resolved and in the remaining 3 patients the lesion was subjected to biopsy as it did not resolve, the biopsy was suggestive of pilocytic astrocytoma). Thus, MRI was shown to have a sensitivity of 83.33% and a specificity of 50% for diagnosing optic chiasmatic-hypothalamic gliomas.
Various lesions like craniopharyngiomas, tuberculomas can mimic optic chiasmatic-hypothalamic gliomas radiologically, and it is not possible to diagnose them with certainty on the basis of radiological findings alone. Biopsy and tissue diagnosis should always be sought before instituting radiotherapy or chemotherapy for optic chiasmatic-hypothalamic gliomas.
Carboplatin plays an important role in the conservative management of retinoblastoma, but is associated with risk of ototoxicity in these young children whose sensory prognosis may be also compromised by their loss of vision. This retrospective study analyzed the impact of carboplatin on hearing in the context of conservative management of children with retinoblastoma.
Data for 175 children treated at the Institut Curie between 1994 and 2002 were analyzed.
Median age at diagnosis was 8 months (0-60). Carboplatin was administered on 3 days (200 mg/m(2)/day) or 5 days (160 mg/m(2)/day) with etoposide and with diode-laser therapy at the dose of 560 mg/m(2) (chemothermotherapy). Median cumulative dose of carboplatin was 2,880 mg/m(2) (560-6,160). Ototoxicity was investigated by pure-tone audiometry and scored by Brock's grading scale before and after treatment. The median follow-up of hearing assessment was 5 years (1.8-11). Ototoxicity was detected in 8 children: 3 grade 1, 1 grade 2, and 2 grade 4. The two patients with grade 4 hearing-loss required a hearing aid. Two children developed bilateral high frequency hearing-loss, considered to be secondary to carboplatin but with less than Brock grade 1. Ototoxicity was observed for a median cumulative dose of carboplatin of 3,120 mg/m(2) (1,200-5,830). Only one child developed ototoxicity during treatment. All other cases were discovered after the last dose of carboplatin with a median interval of 3.7 years (0-7.6). No other risk factor for ototoxicity was able to account for these lesions.
Children receiving carboplatin require long-term audiometric follow-up.
Visual pathway gliomas occur predominantly in young children. Chemotherapy has been increasingly used as a first-line treatment because of the complications caused by radiotherapy and surgery. Nine children between 6 months and 9 years (median age of 4.8 years) were treated with vincristine and carboplatin according to the SIOP (Société Internationale d'Oncologie Pédiatrique) low-grade glioma 1996 protocol. Five patients had evidence of neurofibromatosis type 1. Magnetic resonance imaging (MRI) and ophthalmological assessment were performed during and after treatment. There was a positive response in all children (100%). Three patients developed progressive disease between 8 and 12 months after ceasing treatment. One of them, being only 2.5 years old, was again treated by chemotherapy with partial response on MRI. Patients with neurofibromatosis type 1 never developed progressive disease. Our data suggest that chemotherapy is an effective treatment option in young children with visual pathway gliomas. MRI is an important means of monitoring the tumour response provided that a rigid imaging protocol is used to detect the early tumoral changes.
Thirty glioblastoma patients treated at our institute between April 1998 and September 1999 were randomized in a two-arm study to receive carboplatin plus ACNU intraarterial (IA) chemotherapy (arm A) or cisplatin plus BCNU intravenous (IV) treatment (arm B). After the second course of chemotherapy and before the third cycle they also received concomitant radiotherapy, consisting of a median dose of 56.5 Gy. There were 3 (21.4%) partial responses and 11 (78.6%) disease stabilizations in group A. There were 5 (33%) partial responses and 10 disease stabilizations in group B. Time to tumor progression was 5.2 and 5.8 months for IA and IV treatment respectively. Median survival time was 18.3 months for arm A patients and 18.6 for arm B patients. Our IA chemotherapy schedule has produced no conclusive evidence of benefit compared with intravenous treatment. Moreover, its cost-benefit ratio is not good enough to justify its continued pursuit.
The role of surgery in the management of gadolinium-enhancing pediatric brainstem lesions on magnetic resonance imaging (MRI) has been a matter of open debate. This clinical series correlates radiological and pathological findings to assess the role of contrast enhancement as an indication for surgery with respect to clinical outcome.
We retrospectively reviewed the charts of all pediatric patients admitted to the Johns Hopkins Hospital with a diagnosis of a brainstem tumor between January 1985 and December 2000.
There were a total of 89 patients who met the inclusion criteria. Fifty-seven patients (64.0%) underwent surgical resection while 32 (36%) were treated with radiation and/or chemotherapy. Of the surgical candidates, 57 (100%) had an accompanying MRI scan significant for an enhancing lesion in the midbrain, pons or the medulla. The pathology was consistent with juvenile pilocytic astrocytoma in 30 patients (52.6%) and glioblastoma multiforme in 12 patients (21.1%). The remaining cases consisted of 10 patients (17.5%) with fibrillary astrocytomas, 3 (5.3%) with gangliogliomas, 1 (1.8%) with an oligodendroglioma and 1 (1.8%) with a primitive neuroectodermal tumor. A total of 29 patients had a total surgical resection, 8 a near total resection (>90%), 15 a subtotal resection (50-90%) and 5 a partial resection (<50%). The progression-free survival of all patients was 71.9% at 3 years and 45.6% at 5 years.
This case series illustrates that contrast-enhanced MRI has positive prognostic value in the management of pediatric brainstem gliomas. In our study, the majority of enhancing tumors were low grade and amenable to surgical intervention. Consequently, we recommend surgical resection and pathological diagnosis of all enhancing brainstem tumors with adjuvant therapy reserved for recurrent or unresectable cases.
Intra-arterial (IA) chemotherapy is a form of regional delivery to brain tumors, designed to enhance the intra-tumoral concentrations of a given drug, in comparison with the intravenous route. Drugs that are likely to benefit from IA delivery have a rapid systemic clearance and include carmustine and other nitrosoureas, cisplatin, carboplatin, etoposide, and methotrexate. Clinical studies have demonstrated activity of IA chemotherapy approaches for low- and high-grade gliomas, and for cerebral lymphomas. However, a survival benefit for IA drug delivery, in comparison with intravenous administration, has not been proven in phase III trials. The technique is limited by the potential for significant vascular and neurologic toxicity, including visual loss, stroke, and leukoencephalopathy. More recent studies suggest that toxicity can be reduced by the use of carboplatin- and methotrexate-based regimens. Further clinical studies will be needed to determine the appropriate role for IA chemotherapy in the treatment of primary brain tumors.
The purpose of this study is to analyze clinical aspects and disease-free survival (DFS) in children less than 3 years of age diagnosed with low-grade astrocytoma.
In a period of 24 years (1980-2004), a total of 43 (5.4%) children were registered with these characteristics. Twenty-three patients had pilocytic astrocytoma, 18 diffused, and 2 mixed. Thirty-one (72.1%) children had incomplete surgical tumor resection and 12 (27.9%) had a complete tumor resection. Twelve (27.9%) patients had cranial radiotherapy and 17 (39.5%) received chemotherapy. Overall survival was recorded in 23 (53%). DFS was 50% at 250 months of follow-up for the whole group. DFS for the supratentorial group was 60% at 250 months, whereas, for the infratentorial, it was 22% at 120 months (p = 0.008).
The only favorable prognostic pattern was the supratentorial presentation. Radiotherapy and chemotherapy did not alter the outcome.
Optic pathway gliomas represent approximately 3-5% of childhood intracranial tumors. They usually occur in children during the first decade of life and are seen in 11-30% of patients with neurofibromatosis Type 1 (NF1). Although these tumors are typically low-grade gliomas, the clinical course and natural history are highly variable, making treatment paradigms difficult. Overall, however, they are often indolent tumors that can be observed over time for progression without initial treatment, especially in patients with NF1. Chemotherapy is the first-line treatment for progressive tumors, and radiation therapy is reserved for patients with progressive disease who are older than 5-7 years. Surgery is reserved for large tumors causing mass effect or hydrocephalus and tumors confined to the orbit or unilateral optic nerve.
Optic pathway-hypothalamic gliomas (OPHGs) are rare, often unresectable tumors that mostly occur in childhood. Their biological behavior is unpredictable, although they tend to follow an aggressive clinical course in infants and a benign course in children with neurofibromatosis type 1. Optimal management is still controversial. Nonprogressing OPHGs are usually followed by surveillance alone. Surgery is advocated for progressing tumors to decompress the optic pathways, obtain a quick relief from intracranial hypertension and allow histologic examination (when needed). The current trend is in favor of conservative surgical behavior, except for resectable tumors. Chemotherapy is increasingly used in the management of OPHGs, especially in infants, to delay radiotherapy. Carboplatin and vincristine are the most frequently used drugs, although several chemotherapeutic agents in different combinations are currently employed with good results. Radiotherapy is utilized in children over 5 years of age as an adjuvant or as an alternative to surgery. The prognosis of OPHGs is quite good, with regard to the overall survival rate (70-100% at 5 years), but less favorable in terms of late morbidity.
PURPOSE
Chiasmatic-hypothalamic gliomas are not amenable to surgical resection and therefore are treated with either radiotherapy or chemotherapy. Here we report the use of etoposide (VP-16) administered on a chronic oral schedule as a novel chemotherapeutic approach.
PATIENTS AND METHODS
Fourteen patients, aged 2 to 15 years, were treated with VP-16 after clinical and neuroradiographic tumor progression. Thirteen patients had received prior radiotherapy, and 12 received prior nitrosourea-based chemotherapy. VP-16 was administered orally, each cycle consisting of 50 mg/m2/d on day 1 through 21 and 36 through 57. Clinical and neuroradiographic evaluations were performed during days 58 through 72 before initiation of each cycle of therapy. Complete blood counts were performed weekly.
RESULTS
Treatment-related complications included the following: partial alopecia (seven patients); diarrhea (six); weight loss (five); neutropenia (four); and thrombocytopenia (four). Three patients required transfusion (three RBC; two platelet), and one patient required antibiotic treatment of neutropenic fever. There were no treatment-related deaths. Fourteen patients were assessable, five of whom demonstrated a radiographic response (one complete and four partial); and three patients demonstrated stable disease, with a median duration of response of 8 months.
CONCLUSION
Chronic oral VP-16 is well tolerated, produces modest toxicity, and has apparent activity in this small cohort of patients with recurrent chiasmatic-hypothalamic gliomas.
Background:
Gliomas of the hypothalamus and optic pathways (H/OPG) comprise 5% of pediatric intracranial tumors, present most frequently in patients younger than age 5 years, and may have a more aggressive course in younger children. This study examined clinical characteristics and consequences of treatment of young children diagnosed with H/OPG:
Methods:
The authors reviewed the course, treatment, and outcomes of 46 children diagnosed with H/OPG younger than age 5 years; the median follow-up was 72 months. The median age at diagnosis was 27 months.
Results:
Fifteen (33%) of 46 patients had neurofibromatosis-1 (NF-1). Forty children (87%) had tumor progression in the follow-up period, and tumor growth was less common in children with NF-1. Initial therapy was limited to surgical resection in three and radiation in five children. To postpone radiation until after the age of 5 years, initial therapy was limited to chemotherapy in 32 patients. Radiation was not required in 9 of these patients and was postponed for 40 months (mean) in 17. Of the 46 children, 5 died of tumor progression, 4 became blind, and 20 of 34 evaluable patients had endocrine abnormalities. Endocrinopathy did not correlate with therapy. Ten of 17 children evaluated by questionnaire required special education. There was a trend for educational problems to occur in children who were irradiated before the age of 5 years.
Conclusions:
Gliomas of the hypothalamus and optic pathways and their treatment cause long term morbidity in young children. Chemotherapy postpones radiation effectively, and this delay may reduce neurologic morbidity; however, 60% of children eventually relapse. By contrast, patients with NF-1 have indolent disease.
The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers. Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures). Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment. Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers. Cancer 2000;88:637–47.
Hypothalamic/visual pathway astrocytomas in children are usually quiescent, but certain cases contain aggressive neoplasms that cause progressive neurological and visual deterioration. Radiotherapy is not recommended in young children because of its adverse effects later in life. This report describes the efficacy of a chemotherapeutic regimen. Four young children with hypothalamic/visual pathway astrocytoma, with a mean of 18 months of age at diagnosis, were treated with chemotherapy. Three patients had diencephalic syndrome at the disease's onset. Three patients with pilocytic astrocytoma were histologically verified, and another infant was clinically diagnosed. A combination chemotherapy using cisplatin and vincristine was administered in a total of 8 cycles in 3 children and 4 in one child. One patient who demonstrated renal insufficiency after 4 cycles of this regimen was treated with additional 4 cycles using carboplatin instead of cisplatin. The acute and subacute hematologic and otologic toxicities were mild, and a transient renal insufficiency in a child during chemotherapy improved. After chemotherapy, tumor regression was documented in 3 patients, and the disease was observed to be stable in one patient with an evidence of intratumoral necrosis on MRI. Three patients showed neurological and endocrinological improvements. These results suggest that this regimen is feasible in young children and may be useful as a first-line treatment for hypothalamic/visual pathway astrocytomas, which in turn may allow potentially deleterious irradiation on the maturing brain to be deferred until the disease progresses.
Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m2 for 7 to 8 weeks and VP-16 100 mg/m2 for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, 1 exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor.(ABSTRACT TRUNCATED AT 250 WORDS)
Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.
Chiasmatic-hypothalamic gliomas are not amenable to surgical resection and therefore are treated with either radiotherapy or chemotherapy. Here we report the use of etoposide (VP-16) administered on a chronic oral schedule as a novel chemotherapeutic approach.
Fourteen patients, aged 2 to 15 years, were treated with VP-16 after clinical and neuroradiographic tumor progression. Thirteen patients had received prior radiotherapy, and 12 received prior nitrosourea-based chemotherapy. VP-16 was administered orally, each cycle consisting of 50 mg/m2/d on day 1 through 21 and 36 through 57. Clinical and neuroradiographic evaluations were performed during days 58 through 72 before initiation of each cycle of therapy. Complete blood counts were performed weekly.
Treatment-related complications included the following: partial alopecia (seven patients); diarrhea (six); weight loss (five); neutropenia (four); and thrombocytopenia (four). Three patients required transfusion (three RBC; two platelet), and one patient required antibiotic treatment of neutropenic fever. There were no treatment-related deaths. Fourteen patients were assessable, five of whom demonstrated a radiographic response (one complete and four partial); and three patients demonstrated stable disease, with a median duration of response of 8 months.
Chronic oral VP-16 is well tolerated, produces modest toxicity, and has apparent activity in this small cohort of patients with recurrent chiasmatic-hypothalamic gliomas.
Six patients with optic pathway gliomas who were previously managed with surgery and/or chemotherapy were treated with carboplatin (560 mg/sq m) after radiographic evidence of disease progression. The median age at diagnosis was 2 years (range 4 months to 7 years), and the interval between diagnosis and carboplatin therapy ranged between 7 months and 6.5 years (median 1.8 years). Treatment was given at 4-week intervals and continued until unacceptable toxicity supervened, the disease progressed, or the disease was stable for 12 months. All patients demonstrated disease stability at the outset of the third cycle and continued to do so at the time of this writing. Two patients are 16 and 32 months from initial carboplatin therapy and have been off treatment for 5 and 14 months, respectively; two patients are still receiving therapy at 7 and 11 months after their initial treatment. During the study, two patients developed hypersensitivity to the drug, requiring its discontinuation. Toxicity was minimal, consisting mainly of thrombocytopenia, requiring a one-dose reduction in four of the six treated patients. No platelet transfusions were needed. These results suggest that carboplatin can arrest growth of progressive optic pathway gliomas in children and can allow delay of radiotherapy. A larger trial will be required to define the optimal use of carboplatin in the treatment of low-grade gliomas in children.
This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs.
Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity.
Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated.
Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.
Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical benefit. The patients were aged 2.5 to 8 years. Three patients presented with PA localized in the posterior fossa, initially treated with surgical resection (n = 3) and radiotherapy (n = 1). Leptomeningeal dissemination occurred at 32, 44, and 8 months from diagnosis, respectively. The fourth patient presented with an optic pathway tumor with leptomeningeal dissemination at diagnosis. At commencement of cyclophosphamide therapy, disease was present in the subarachnoid space (intracranial, n = 2; spinal, n = 4), cerebral ventricles (n = 2), and primary site (n = 3). Histology was identical at diagnosis and recurrence in the two biopsied cases and cerebrospinal fluid was negative in all cases. Treatment was with cyclophosphamide 4-5 g/m2/cycle given every 4 weeks for a total of two cycles (n = 1) and four cycles (n = 3). One patient achieved disease stabilization (duration 27 months at the time of publication) and three patients experienced significant reductions in tumor burden. Subsequent intrathecal therapy was administered to two patients. Two patients developed disease progression at 10 and 9 months from cessation of chemotherapy. The one re-treated patient responded to further, lower dose, cyclophosphamide. This is the first report of the use of high dose cyclophosphamide for disseminated PA. The recurrence of disease in two cases with a further response to lower dose cyclophosphamide has implications for the optimal duration of therapy for these low grade, aggressive tumors.
The treatment of visual pathway gliomas is controversial. The many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic gliomas are difficult to interpret for several reasons. First the natural history of these tumors is erratic with some reports suggesting that most visual pathway gliomas are hamartomas and follow an indolent course, and others reporting 10-year survival rates of close to 60%. Second, earlier studies did not clearly indicate which patients had neurofibromatosis type 1 (NF1) and recent evidence suggests that the natural history of optic gliomas is more favorable in patients with NFL Third the methods and accuracy of diagnosis have changed dramatically and patients diagnosed before and after the[/p] advent of CT/MR imaging have often been included in the same series.
While surgical resection is usually not a viable option for definitive treatment of these tumors, recent studies have shown favorable results after subtotal resection in selected patients. The efficacy of radiotherapy has not been unequivocally demonstrated and treatment-related morbidity has become a major concern, in particular, adverse effects on cognition and growth. Chemotherapy has been advanced as an viable alternative to avoid or delay the adverse affects of RT, but the long-term outcome benefits and adverse effects of treatment are just being defined. Despite the limitations of currently available information, sufficient data are now available to rational management quotelines for the majority of children with chiasmatic/hypothalamic gliomas.
Neurofibromatosis 1 (NF1) is a common multisystem disorder that is frequently associated with neoplastic and non-neoplastic lesions within the central nervous system. Improvements in neuroimaging have led to increased detection of both types of lesions. Focal areas of increased T2 signal represent the most common abnormalities detected. The vast majority of such lesions are non-neoplastic and fluctuate in number and size during childhood. Optic pathway tumors are second in frequency and generally manifest an indolent natural history, although some lesions will increase in size over time and lead to progressive visual impairment. A smaller percentage of patients will develop gliomas within the cerebral and cerebellar hemispheres of brain-stem. This article will review areas of controversy in the evaluation and follow-up of patients with NF1 and will present our approach to these issues. We will also discuss therapeutic considerations in these patients that take into account the unique features of the underlying disorder.
The effect of radiosurgery on optic gliomas is uncertain. We report two cases of low-grade glioma of the optic nerve and chiasm treated by transcranial subtotal removal and Gamma Knife radiosurgery. The first case was a 2-year-old boy, admitted with visual disturbance and nystagmus. Histopathological examination showed a pilocytic astrocytoma. The tumor volume was 14.4 cm3. Dose planning was performed using axial and coronal T1-weighted enhanced images. The marginal dose was 12 Gy at the 40% isodose line. The dose to the optic apparatus was less than 9 Gy. The second case was a 47-year-old woman, admitted to our hospital with headache and visual disturbance. The histopathological findings showed a fibrillary astrocytoma. The tumor volume was 12.3 cm3. The marginal dose was 14.4 Gy at the 40% isodose curve. The follow-up periods for the two cases were 24 and 43 months, respectively. In both cases the most recent follow-up magnetic resonance scan showed a marked decrease in tumor size, and visual symptoms were improved. No postradiosurgical complications have developed to date. Gamma Knife radiosurgery could be an effective adjuvant therapy for low-grade optic glioma. However, long-term follow-up is required for further evaluation of the efficacy and potential side effects.
An 18 year-old woman received radiation therapy for hypothalamic astrocytoma at the age of 11 years. She developed progressive cerebral occlusive vascular disease with moyamoya vessels formation in both carotid systems. Apart from diabetes mellitus, she had no other risk factors for occlusive cerebrovascular disease. The site of occlusion was confined to the field of radiation and the development of moyamoya vessels strongly suggestive of a radiation-induced cause. Radiation therapy around the sella and parasellar region appears to be the most common risk factor for this vasculopathy. Progressive irradiation-induced cerebral vasculopathy is due to accelerated atherosclerosis.
We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy.
Descriptive retrospective study using case note review analysis.
The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment.
Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function.
Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery.
Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.
This article reviews historical aspects of the blood-brain barrier (BBB) and recent advances in mechanisms to deliver therapeutic agents across the BBB for the treatment of intracerebral tumors and other neurological diseases.
The development of the osmotic BBB disruption procedure as a clinically useful technique is described. Osmotic BBB disruption is contrasted with alternative methods for opening or bypassing the BBB, including pharmacological modification of the BBB with bradykinin and direct intracerebral infusion.
Laboratory studies have played a fundamental role in advancing our understanding of the BBB and delivery of agents to brain. Preclinical animal studies will continue to serve an integral function in our efforts to improve the diagnosis and treatment of a number of neurological disorders. Techniques involving the modification of the BBB and/or blood-tumor barrier to increase delivery of therapeutic agents have been advanced to clinical trials in patients with brain tumors with very favorable results.
Improving delivery of agents to the brain will play a major role in the therapeutic outcome of brain neoplasms. As techniques for gene therapy are advanced, manipulation of the BBB also may be important in the treatment of central nervous system genetic disorders.
Two cases of recurrent pilocytic astrocytoma with leptomeningeal dissemination (LMD) are described. A 6-year-old boy presented with a cerebellar tumor, which was subtotally removed. Tumor recurrence with LMD occurred 4 years later. Reoperation for tumor removal followed by craniospinal irradiation stabilized the LMD over 5 years. A 4-year-old girl presented with a chiasmatic-hypothalamic tumor. Partial removal of the tumor was followed by radiation therapy. Tumor regrowth with LMD occurred 4 years later and was managed by reoperation, chemotherapy and radiotherapy. Tumor recurrence with LMD can be stabilized by multimodal treatment without tumor progression.
Occlusive vasculopathy is a potential complication of radiotherapy in children with optic pathway glioma. With a median follow-up of 7 years, 13 of 69 children in this study developed clinical and radiological signs of occlusive vasculopathy after radiotherapy within a median interval of 36 months. The major risk factor was neurofibromatosis type 1. Radiotherapy should no longer be the first treatment in these settings. When radiotherapy is unavoidable, regular screening for cerebral vasculopathy is mandatory, as preventive treatment is available.
Management of low grade optic glioma in children and adolescents remains controversial. Treatment with chemotherapy may delay or eliminate the need for radiation therapy. Children with newly diagnosed optic chiasm glioma were eligible for enrollment in this phase II trial and received intravenous carboplatin (CBDCA) (560 mg/m2) every four weeks. Patients were monitored closely for toxicity and tumor status. Twelve children were enrolled. Six patients had stable disease, four a partial response and two progressed on therapy. Overall progression free survival was 83 +/- 11%. The median duration of follow-up was 38.6 months (range 18-63 months). No deaths were noted in our series. Thrombocytopenia was the major toxicity, and two patients required platelet transfusions. One child developed an urticarial reaction requiring discontinuation of therapy. Another child developed unilateral high frequency hearing loss. No renal toxicity was encountered. We have demonstrated that carboplatin can eliminate or delay radiation therapy in children and adolescents with low grade optic glioma. CBDCA deserves further investigation in larger clinical trials as a treatment for children with optic chiasm glioma.
To evaluate the rate of complications associated with diagnostic cerebral angiography accompanied by intraarterial chemotherapy for the treatment of primary and metastatic brain tumors.
Three hundred ninety-two consecutive transfemoral cerebral angiographic procedures accompanied by intraarterial chemotherapy were performed in 48 patients (28 men, 20 women), and complications were evaluated.
The most common local complications were groin hematomas, which occurred in 10 (2.6%) of the 392 procedures and none of which required therapy. Two carotid arterial dissections (0.5%) were reported in two patients who were asymptomatic and did not require further treatment. Both improved at follow-up examinations. Only one patient required surgery for a delayed popliteal embolus. Systemic transient complications occurred five times (1.3%). There were seven (1.8%) transient neurologic events, which were paresis and visual disturbances. Six (1.5%) transient seizure events were recorded. There were no permanent neurologic complications.
Intraarterial chemotherapy for brain tumors is a safe procedure with a low complication rate.
Optic chiasmatic-hypothalamic gliomas in children with radiation therapy
- E Alshail
- Jt Rutka
- Becker
- Le
Alshail E, Rutka JT, Becker LE, et al. Optic chiasmatic-hypothalamic gliomas in children with radiation therapy. Radiother Oncol 1997;45:11–15