PubMed Health⌕ Search

Biomedical subjects

Amar Gajjar

Publications and source records attributed to Amar Gajjar.

At least 37 records · Page 2Linked to original sources

Development and validation of limited sampling models for topotecan lactone pharmacokinetic studies in children.

PURPOSE: To develop and validate a pharmacokinetic limited sampling model (LSM) for intravenous and oral topotecan pharmacokinetic studies in children. METHODS: Topotecan lactone concentration-time data from five trials were used to develop and validate LSM for intravenous and oral topotecan. Based on full sampling from one intravenous study (30 patients; 195 studies), a LSM for intravenous topotecan was determined using a modification of the D-optimality algorithm. For oral topotecan we used full sampling data from one oral topotecan study (27 patients; 47 studies) to develop an LSM. Accuracy and bias of each LSM were determined relative to the full sampling method. Predictive performance of the LSM was validated using additional data and Monte-Carlo simulations based on these data. RESULTS: LSM for intravenous topotecan includes: 5 min, 1.5, and 2.5 h after the end of the 30 min infusion. The median accuracy (absolute predicted error) and bias (predicted error) are < or =8% and < or =6.1%, respectively. For oral topotecan, the optimal LSM includes: 15 min, 1.5, and 6 h. The median accuracy and bias are 6% and 4%, respectively. CONCLUSIONS: Our results indicate that the optimal sampling times for the intravenous LSM for topotecan in children consist of: predose, and 5 min, 1.5, and 2.5 h after the end of infusion. For oral topotecan the sample times are predose, 15 min, 1.5, and 6 h after dose administration. These LSM are invaluable to children receiving topotecan because it minimizes inconvenience and blood collection.

Administration, Oral↗

Attention and memory functioning among pediatric patients with medulloblastoma.

OBJECTIVE: To test the hypotheses that memory and attention deficits are prevalent in survivors of childhood medulloblastoma (MB) and that these deficits are associated with problems with academic achievement. METHODS: The medical charts of 38 child survivors of MB, who were administered the California Verbal Learning Test, Child Version (CVLT-C), Conners' Continuous Performance Test (CPT), and the Wechsler Individual Achievement Test (WIAT) as part of a comprehensive neurocognitive test battery, were retrospectively reviewed. RESULTS: Although no significant verbal memory deficits were found, 8 of 11 CPT variables were significantly below the standardization mean (p < or = .01). Additionally, stepwise regression analyses found that increased omission errors were significantly associated with lower reading and math performance (p < or = .01). CONCLUSIONS: These findings confirm previous reports of attention deficits among survivors of MB and provide a better understanding of how the dysfunction of particular attentional substrates (e.g., perceptual sensitivity, response bias) may result in learning problems in this population.

Adolescent↗

Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.

Central Nervous System Neoplasms↗

Development of a pharmacokinetic limited sampling model for temozolomide and its active metabolite MTIC.

PURPOSE: To develop a pharmacokinetic limited sampling model (LSM) for temozolomide and its metabolite MTIC in infants and children. METHODS: LSMs consisting of either two or four samples were determined using a modification of the D-optimality algorithm. This accounted for prior distribution of temozolomide and MTIC pharmacokinetic parameters based on full pharmacokinetic sampling from 38 patients with 120 pharmacokinetic studies (dosage range 145-200 mg/m(2) per day orally). Accuracy and bias of each LSM were determined relative to the full sampling method. We also assessed the predictive performance of the LSMs using Monte-Carlo simulations. RESULTS: The four strategies generated from the D-optimality algorithm were as follows: LSM 1=0.25, 1.25, and 3 h; LSM 2=0.25, 1.25, and 6 h; LSM 3=0.25, 0.5, 1.25, and 3 h; LSM 4=0.25, 0.5, 1.25, and 6 h. LSM 2 demonstrated the best combination of low bias [0.1% (-8.9%, 11%) and 11% (4.3%, 15%)] and high accuracy [-1.0% (-12%, 24%) and 14% (7.9%, 37%)] for temozolomide clearance and MTIC AUC, respectively. Furthermore, adding a fourth sample (e.g., LSM 4) did not substantially decrease the bias or increase the accuracy for temozolomide clearance or MTIC AUC. Results from Monte-Carlo simulations also revealed that LSM 2 had the best combination of lowest bias (0.1+/-6.1% and -0.8+/-6.5%), and the highest accuracy (4.5+/-4.1% and 5.0+/-4.3%) for temozolomide clearance and MTIC apparent clearance, respectively. CONCLUSIONS: Using data derived from our population analysis, the sampling times for a limited sample pharmacokinetic model for temozolomide and MTIC in children are prior to the temozolomide dose, and 15 min, 1.25 h and 6 h after the dose.

Antineoplastic Agents, Alkylating↗

Phase I clinical trial of mafosfamide in infants and children aged 3 years or younger with newly diagnosed embryonal tumors: a pediatric brain tumor consortium study (PBTC-001).

PURPOSE: A phase I trial of intrathecal (IT) mafosfamide was performed to determine the optimal dose, dose-limiting toxicities, and incidence and severity of other toxicities when administered in association with concomitant multiagent systemic chemotherapy to children younger than 3 years with newly diagnosed embryonal tumors. PATIENTS AND METHODS: Twenty-five assessable patients received IT mafosfamide at one of six dose levels ranging from 5 mg to 17 mg. Patients were premedicated with dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. RESULTS: Irritability, presumably secondary to pain or headache during mafosfamide administration, was dose limiting in two of three patients at the 17-mg dose level. The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg. CONCLUSION: The maximum tolerated dose and recommended phase II dose of IT mafosfamide in patients younger than 3 years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess the efficacy of regional therapy with IT mafosfamide administered with intensive systemic chemotherapy in children younger than 3 years with primary intracranial embryonal tumors is now in progress.

Affect↗

Bone marrow recurrence after initial intensive treatment for childhood acute lymphoblastic leukemia.

BACKGROUND: The authors studied the clinical outcome of 106 children with acute lymphoblastic leukemia (ALL) who developed a bone marrow recurrence as the first adverse event after contemporary intensified therapy. METHODS: Endpoints were the rates and lengths of second remission, the cumulative incidence of second hematologic recurrence, second event-free survival (EFS), and survival. RESULTS: Bone marrow recurrences were isolated in 79 patients, and combined with an extramedullary site in 27 patients. The median time to recurrence was 2.6 years (range, 0.3-11.6 years). Seventy-six patients (71.7%) attained a second remission (median length, 0.7 year; range, 0.03-13.3 years). The 5-year survival probability among all patients was 24.2% +/- 4.2% (standard error). On multivariate analysis, time to first disease recurrence and blast cell lineage were found to be independent predictors of a second EFS (P = 0.008 and P = 0.028, respectively). The 5-year EFS estimate in patients with an initial disease remission of >/= 36 months was 42.6% +/- 7.8% but was only 12.5% +/- 3.9% among children with a short duration of disease remission (< 36 months). These estimates were 28.7% +/- 4.9% and 5.0% +/- 3.4%, respectively, for B blast and T blast cell lineages. CONCLUSIONS: Despite acceptable long-term second EFS rates for certain subgroups, overall bone marrow recurrence after intensified first-line therapy for childhood ALL signals a poor outcome.

Adolescent↗

Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98).

BACKGROUND: The role of chemotherapy in the treatment of children with newly diagnosed diffuse brainstem glioma is uncertain. In the current study, the authors tested the efficacy of temozolomide treatment after radiotherapy (RT) in this setting. METHODS: Patients ages 3-21 years were eligible for the current multiinstitutional study. An optional window therapy regimen consisting of 2 cycles of intravenous irinotecan (10 doses of 20 mg/m2 per day separated by 2 days of rest per cycle) was delivered over 6 weeks and was followed by conventionally fractionated RT. The 5-day schedule of temozolomide (200 mg/m2 per day) was initiated 4 weeks after RT and was continued for a total of 6 cycles. The pharmacokinetics of temozolomide and its active metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), were analyzed during Cycles 1 and 3. RESULTS: Thirty-three patients (median age at diagnosis, 6.4 years) were enrolled. Of the 16 patients who received window therapy, 6 had irinotecan treatment discontinued due to clinical progression (n=5) or toxicity (n=1); the remaining 10 experienced disease stabilization after 2 cycles. All patients completed RT (median dose, 55.8 gray). Twenty-nine patients received a combined total of 125 cycles of temozolomide. Grade 3/4 neutropenia and thrombocytopenia occurred in 33% and 29% of all temozolomide cycles, respectively. In approximately one-third of the cycles, dose reduction was required due to myelosuppression. No correlation was demonstrated between temozolomide/MTIC exposure and myelosuppression at the conclusion of Cycle 1. All patients died of disease progression (median survival, 12 months). The estimated 1-year survival rate was 48% (standard error, 8%). CONCLUSIONS: The administration of temozolomide after RT did not alter the poor prognosis associated with newly diagnosed diffuse brainstem glioma in children.

Administration, Oral↗

A knowledge-guided active contour method of segmentation of cerebella on MR images of pediatric patients with medulloblastoma.

PURPOSE: To develop an automated method for identification of the cerebella on magnetic resonance (MR) images of patients with medulloblastoma. MATERIALS AND METHODS: The method used a template constructed from 10 patients' aligned MR head images, and the contour of this template was superimposed on the aligned data set of a given patient as the starting contour. The starting contour was then actively adjusted to locate the boundary of the cerebellum of the given patient. Morphologic operations were applied to the outlined volume to generate cerebellum images. The method was then applied to data sets of 20 other patients to generate cerebellum images and volumetric results. RESULTS: Comparison of the automatically generated cerebellum images with two sets of manually traced images showed a strong correlation between the automatically and manually generated volumetric results (correlation coefficient, 0.97). The average Jaccard similarities were 0.89 and 0.88 in comparison to each of two manually traced images, respectively. The same comparisons yielded average kappa indexes of 0.94 and 0.93, respectively. CONCLUSION: The method was robust and accurate for cerebellum segmentation on MR images of patients with medulloblastoma. The method may be applied to investigations that require segmentation and quantitative measurement of MR images of the cerebellum.

Adolescent↗

Molecular biology of medulloblastoma: will it ever make a difference to clinical management?

Over the last 10 years approximately 750 children with medulloblastoma have been treated on consortia based clinical trials at an estimated cost of over 150 million US dollars. Despite this enormous effort, no meaningful molecular data has been generated that will inform the next generation of clinical studies. It is imperative that the neuro-oncology community give greater priority to studies of medulloblastoma molecular biology: unless we do this our patients will face a bleak future in which there is no accurate disease-risk stratification tool and no effective new treatments. We review some of the reasons we have failed to translate knowledge of medulloblastoma disease biology to the clinic and look forward to the next generation of clinical and molecular studies that are seeking to correct this.

Antineoplastic Agents↗

Radial glia cells are candidate stem cells of ependymoma.

Tumors of the same histologic type often comprise clinically and molecularly distinct subgroups; however, the etiology of these subgroups is unknown. Here, we report that histologically identical, but genetically distinct, ependymomas exhibit patterns of gene expression that recapitulate those of radial glia cells in the corresponding region of the central nervous system. Cancer stem cells isolated from ependymomas displayed a radial glia phenotype and formed tumors when orthotopically transplanted in mice. These findings identify restricted populations of radial glia cells as candidate stem cells of the different subgroups of ependymoma, and they support a general hypothesis that subgroups of the same histologic tumor type are generated by different populations of progenitor cells in the tissues of origin.

Animals↗

Seizures in children with primary brain tumors: incidence and long-term outcome.

PURPOSE: To estimate the incidence and long-term outcome of brain tumor related seizures in children and to identify risk factors for adverse seizure outcome. METHODS: Analysis of medical records of children treated for brain tumor and seizures in a single institution. Children were identified from hospital database and neurology clinic records. Seizure status was characterized for the 6 months prior to most recent follow-up. RESULTS: Median follow-up after first seizure of the 157 analyzed children was 3.3 years. Tumor location was supratentorial in 81% and posterior fossa in 19%. Initial anti-epileptic drugs were phenytoin (n=52), carbamazepine (n=38), phenobarbital (n=14), gabapentin (n=31), or others (n=22). Seizures were controlled in 65% of the children and uncontrolled in 35% (17% intractable). Gabapentin showed a trend toward better seizure control (p=0.06). Neurologic deficit, T2 peri-cavity hyperintensity, and EEG slow waves were independently predictive of uncontrolled seizures by multivariate analysis. CONCLUSIONS: T2 peri-cavity hyperintensity, focal neurologic deficits, and EEG slow waves predict poor seizure control in children with brain tumors. Seizures can be controlled in most patients with brain tumors. Gabapentin use as first anti-epileptic drug needs to be studied prospectively.

Adolescent↗

Atypical white matter volume development in children following craniospinal irradiation.

Most children with medulloblastoma (MB), the second most common pediatric brain tumor, have a 70% probability of survival. However, survivors who receive aggressive therapy are at significant risk of cognitive deficits that have been associated with lower volumes of normal-appearing white matter (NAWM). We hypothesized that cranial irradiation inhibited normal brain volume development in these survivors. We retrospectively analyzed 324 MRI studies of 52 patients with histologically proven MB treated with surgery and 35 to 40 Gy craniospinal irradiation, with or without chemotherapy. The volume of NAWM and that of cerebrospinal fluid were quantified from a single index section and compared with those of healthy, age-similar control subjects. A quadratic random coefficient model was used to identify trends in brain volume with increasing age. Patients treated for MB at younger ages demonstrated substantially less development of NAWM volume than did their healthy peers. Younger age at the time of irradiation and the need for a ventricular shunt were significantly associated with reduced NAWM volume. NAWM and craniospinal fluid volume differences between patients who had shunts and those without resolved over a period of four to five years. NAWM volume is known to be associated with neurocognitive test performance, which shows deficiencies after cranial irradiation early in life. Therefore, volumetric monitoring of brain development can be used to guide the care of survivors, assess the toxicity of previous and current clinical trials, and aid in the design of therapies that minimize toxicity.

Abnormalities, Radiation-Induced↗

Diffusion tensor imaging of intraaxial tumors at the cervicomedullary and pontomedullary junctions. Report of two cases.

Brainstem gliomas are a heterogeneous group of lesions that account for 15% of all pediatric tumors of the central nervous system. Diagnosis and treatment planning for these tumors is based on the observation of Epstein and Farmer that the growth of lesions with low malignant potential is limited by the anatomical structures of the brainstem. Surgery is offered only to those patients with a high probability of harboring a low-grade tumor, because the attendant risk for significant morbidity outweighs the therapeutic benefit of debulking the tumor in cases of high-grade tumors. The authors report two cases that highlight the potential of diffusion tensor (DT) imaging to identify local white matter tracts in the pons, medulla, and cervical cord and to improve the preoperative assessment of low-grade gliomas. Preoperative DT imaging in both cases demonstrated that the white matter tracts were displaced by the bulk of the low-grade tumors but were structurally preserved. Intraoperative and neurological findings were consistent with the preoperative interpretation of the DT images. These cases demonstrate that DT imaging is a useful method for visualizing the relationship between tumor and normal brainstem white matter architecture, as well as for improving the surgical evaluation and management of pediatric brainstem tumors.

Adolescent↗

White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor.

PURPOSE: White matter lesions (WMLs) have been described as a delayed effect of cranial irradiation in children with brain tumors, or a transient subacute effect characterized by an intralesional or perilesional reaction. We report the occurrence of subacute WMLs detected by magnetic resonance imaging (MRI) in children treated for medulloblastoma or primitive neuroectodermal tumor (PNET) and document the associated clinical, radiologic, and neurocognitive findings. PATIENTS AND METHODS: Among 134 patients with medulloblastoma or supratentorial PNET treated prospectively with risk-adjusted craniospinal irradiation and conformal boost to the tumor bed, followed by four high-dose chemotherapy (HDC) cycles with stem-cell rescue, 22 developed WMLs on T1-weighted imaging with and without contrast and/or T2-weighted imaging on MRI. Patients had > or = 12 months of follow-up. Neurocognitive assessments included intelligence quotient (IQ) tests and tests of academic achievement. RESULTS: Twenty-two patients developed WMLs at a median of 7.8 months after starting therapy (range, 1.9 to 13.0 months). Lesions were predominantly in the pons (n = 8) and cerebellum (n = 6). Sixteen patients (73%) had WML resolution at a median of 6.2 months (range, 1.68 to 23.5 months) after onset; two patients developed necrosis and atrophy. Three developed persistent neurologic deficits. Cumulative incidence of WMLs at 1 year was 15% +/- 3%. Patients with WMLs had a significant decline in estimated IQ (-2.5 per year; P = .03) and math (-4.5 per year; P = .003) scores. CONCLUSION: WMLs in medulloblastoma or PNET patients treated with conformal radiotherapy and HDC are typically transient and asymptomatic, and may mimic early tumor recurrence. A minority of patients with WMLs develop permanent neurologic deficits and imaging changes. Overall, the presence of WMLs is associated with greater neurocognitive decline.

Adolescent↗

Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.

PURPOSE: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. PATIENTS AND METHODS: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL.h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. RESULTS: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. CONCLUSION: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.

Adolescent↗

Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children's Research Hospital experience.

BACKGROUND: Details on second neoplasms (SNs) following pediatric central nervous system (CNS) tumors are scant, because of the rarity of such SNs. The goal of the current study was to investigate and characterize these rare SNs. METHODS: The authors reviewed clinical and treatment data on all institutional patients age < 22 years at diagnosis of a primary CNS tumor who developed any type of SN. Patients with neurofibromatosis type 1 were excluded. Cumulative incidence rates were estimated, and putative risk factors were analyzed. RESULTS: The SNs investigated in the current study included 10 gliomas (42%), 5 meningiomas (21%), 2 desmoid tumors, 2 myelodysplastic syndromes, 2 basal cell carcinomas, 1 leukemia, 1 malignant fibrous histiocytoma, and 1 thyroid carcinoma. Twenty-one patients had previously received radiotherapy, and 12 patients had received chemotherapy. The SN was related to a genetic cause in 7 patients (29%). Eleven patients died of their SNs, including 8 patients with glioma and 2 patients with myelodysplastic syndromes. The estimated 15-year cumulative incidence rate for malignant SNs was 4%. Children with choroid plexus tumors had an estimated 10-year cumulative incidence rate of 20.2%; 2 of those patients had germline TP53 mutations. Age </= 2 years was a significant risk factor (P = 0.016) for development of an SN only when patients with genetic conditions were included in the analysis. No significant difference in the estimated cumulative incidence of SNs was found among patients who had received different types of therapy. CONCLUSIONS: The risk of lethal SNs after pediatric CNS tumors is small. Young patients and patients with choroid plexus tumors appear to have an increased risk of SNs that is associated with genetic factors.

Adolescent↗

Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma.

PURPOSE: To assess the feasibility of performing central molecular analyses of fresh medulloblastomas obtained from multiple institutions and using these data to identify prognostic markers for contemporaneously treated patients. MATERIALS AND METHODS: Ninety-seven samples of medulloblastoma were collected. Tumor content in samples was judged by frozen section review. Tumor ERBB2 protein and MYCC, MYCN, and TRKC mRNA levels were measured blind to clinical details using Western blotting and real-time polymerase chain reaction, respectively. Histopathologic and clinical review of each case was also performed. All data were subjected to independent statistical analysis. RESULTS: Sample acquisition and analysis times ranged from 3 to 6 days. Eighty-six samples contained sufficient tumor for analysis, including 38 classic, 30 nodular desmoplastic, and 18 large-cell anaplastic (LCA) medulloblastomas. Protein and mRNA were extracted from 81 and 49 tumors, respectively. ERBB2 was detected in 40% (n=32 of 81) of tumors, most frequently in LCA disease (P=.005), and was independently associated with a poor prognosis (P=.031). A combination of clinical characteristics and ERBB2 expression provided a highly accurate means of discriminating disease risk. One hundred percent (n=26) of children with clinical average-risk, ERBB2-negative disease were alive at 5 years, with a median follow-up of 5.6 years, compared with only 54% for children with average-risk, ERBB2-positive tumors (n=13; P=.0001). TRKC, MYCC, and MYCN expression and histopathologic subtype were not associated with prognosis in this study. CONCLUSION: Central and rapid molecular analysis of frozen medulloblastomas collected from multiple institutions is feasible. ERBB2 expression and clinical risk factors together constitute a highly accurate disease risk stratification tool.

Adolescent↗

Clinically evident venous thromboembolic events in children with brain tumors.

We evaluated the incidence and significance of central venous access device dysfunction and symptomatic major thrombosis in 253 pediatric patients with brain tumors. Central venous access device dysfunction was a common complication (28.4%) and was associated with major thrombosis development and a reduced overall survival rate. Major thrombosis was relatively uncommon (2.8%).

Brain Neoplasms↗