J E C Bromberg

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (21)91.63 Total impact

  • M J van den Bent, J E C Bromberg
    Handbook of Clinical Neurology 01/2012; 105:467-84.
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    Journal of Neurology 08/2011; 259(3):559-61. · 3.58 Impact Factor
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    ABSTRACT: Palliative sedation (PS) is necessary in a significant percentage of patients dying on an acute palliative care unit (PCU). Common indications are terminal restlessness, pain and dyspnoea. On our PCU, terminal restlessness was the main indication for PS but pain was the most prevalent symptom during admission. Because delirium is often drug induced in terminal cancer patients and opioids are amongst the most frequently implicated drugs, we hypothesised that the underlying pain problem and its treatment might have been related to the need for sedation. To test this hypothesis, we did a retrospective analysis on the use of medication with potential cognitive side-effects, focusing on analgesics, in 68 patients who died on the PCU after PS and 89 patients who died without PS. Ultimately sedated patients used opioids in significantly higher doses; they were more often treated with a rotation to another opioid and with amitriptyline. The dose of opioids used at various time points between admission and death was strongly related to the probability of PS. Our findings support the hypothesis that, although pain was not the main indication for PS, pain and its treatment might have been primarily related to the need for palliative sedation in this patient cohort.
    European journal of cancer (Oxford, England: 1990) 07/2011; 47(15):2341-6. · 4.12 Impact Factor
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    ABSTRACT: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.
    Annals of Oncology 02/2011; 22(9):2144-9. · 7.38 Impact Factor
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    ABSTRACT: Objective Paraneoplastic neurological syndromes associated with anti-Hu antibodies (Hu-PNS) are mediated by a T-cell immune response that is directed against the Hu antigens. In pregnancy, many Th1-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis regress. We hypothesised that this decreased disease activity during pregnancy may be related to high human chorionic gonadotropin (hCG) levels.Methods15 Hu-PNS patients were treated in a prospective, uncontrolled and unblinded trial with 10 000 IU daily of hCG administered by intramuscular injection during 12 weeks. Primary outcome measures were functional improvement defined as a decrease of one or more points on the modified Rankin Scale (mRS) or stabilisation in patients with mRS score ≤3 and improvement of neurological impairment assessed with the Edinburgh Functional Impairment Tests (EFIT). Secondary end points included the change in activities of daily living as evaluated using the Barthel Index.ResultsSeven of 15 patients (47%) improved on the mRS or stabilised at mRS score ≤3. Four patients (27%) showed significant improvement of neurological impairment as indicated by an overall Edinburgh Functional Impairment Tests score of ≥1 point. Five patients improved on the Barthel Index (33%).Conclusion Comparison with previous studies suggests that hCG may have immunomodulatory activity and may modify the course of Hu-PNS, although well-established confounding factors may have contributed in this uncontrolled trial.
    Journal of neurology, neurosurgery, and psychiatry 01/2010; 81(12):1341-1344. · 4.87 Impact Factor
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    ABSTRACT: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment. We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy. IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment. These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.
    Neurology 11/2009; 73(21):1792-5. · 8.30 Impact Factor
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    ABSTRACT: Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth factor receptor (EGFR) gene amplification (EGFR(amp)), and loss of chromosome 10 or 10q offers additional prognostic information to the histological diagnosis and would allow molecular subtyping. For this study, we used the clinical data and tumor samples of the patients included in multicenter prospective phase III European Organisation for Research and Treatment of Cancer (EORTC) study 26951 on the effects of adjuvant procarbazine, chloroethyl cyclohexylnitrosourea (lomustine), and vincristine chemotherapy in anaplastic oligodendroglial tumors. Fluorescence in situ hybridization was used to assess copy number aberrations of chromosome 1p, 19q, 7, 10, and 10q and EGFR. Three different analyses were performed: on all included patients based on local pathology diagnosis, on the patients with confirmed anaplastic oligodendroglial tumors on central pathology review, and on this latter group but after excluding anaplastic oligoastrocytoma (AOA) with necrosis. As a reference set for glioblastoma multiforme (GBM), patients from the prospective randomized phase III study on GBM (EORTC 26981) were used as a benchmark. In 257 of 368 patients, central pathology review confirmed the presence of an anaplastic oligodendroglial tumor. Tumors with combined 1p and 19q loss (1p(loss)19q(loss)) were histopathologically diagnosed as anaplastic oligodendroglioma, were more frequently located in the frontal lobe, and had a better outcome. Anaplastic oligodendroglial tumors with EGFR(amp) were more frequently AOA, were more often localized outside the frontal lobe, and had a survival similar to that for GBM. Survival of patients with AOA harboring necrosis was in a similar range as for GBM, while patients with AOA with only endothelial proliferation had better overall survival. In univariate analyses, all molecular factors except loss of 10q were of prognostic significance, but on multivariate analysis a histopathological diagnosis of AOA, necrosis, and 1p(loss)19q(loss) remained independent prognostic factors. AOA tumors with necrosis are to be considered WHO grade IV tumors (GBM). Of all molecular markers analyzed in this study, especially loss of 1p/19q carried prognostic significance, while the others contributed little prognostic value to classical histology.
    Neuro-Oncology 03/2009; 11(6):737-46. · 6.18 Impact Factor
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    Jacolien E C Bromberg, Martin J van den Bent
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    ABSTRACT: Oligodendroglial tumors continue to receive much attention because of their relative sensitivity to chemotherapy. The histological diagnosis of oligodendroglial tumors is subject to considerable interobserver variation. The revised 2007 World Health Organization classification of brain tumors no longer accepts the diagnosis "mixed anaplastic oligoastrocytoma" if necrosis is present; these tumors should be considered glioblastomas (perhaps with oligodendroglial features). The 1p/19q codeletion that is associated with sensitivity to chemotherapy is mediated by an unbalanced translocation of 19p to 1q. Randomized studies have shown that patients with 1p/19q codeleted tumors also have a better outcome with radiotherapy. Histologically more atypical tumors are less likely to have this 1p/19q codeletion; here, other alterations usually associated with astrocytic tumors are often found. Some patients with tumors with classic histological features but no 1p/19q codeletion still have a very favorable prognosis. Currently, the best approach for newly diagnosed anaplastic oligodendroglial tumors is unclear. Early adjuvant chemotherapy does not provide a better outcome than chemotherapy at the time of progression. The value of combined chemoirradiation with temozolomide has not been proven in these tumors, and could at least theoretically be associated with greater neurotoxicity. Tumors with 1p and 19q loss can also be managed with early chemotherapy, while deferring radiotherapy to the time of further progression. The presently available second-line chemotherapy results are modest, and better salvage treatments are necessary. The molecular explanation for the greater sensitivity of 1p/19q codeleted tumors is still unclear, and this could, in part, be explained by more frequent MGMT promoter gene methylation.
    The Oncologist 02/2009; 14(2):155-63. · 4.10 Impact Factor
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    ABSTRACT: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population.
    Annals of Oncology 08/2007; 18(7):1145-51. · 7.38 Impact Factor
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    ABSTRACT: To assess the diagnostic accuracy of flow cytometric immunophenotyping in comparison with classic cytomorphology for diagnosing CNS localizations of hematologic malignancies, and to evaluate the implications of CSF pleocytosis and protein content in this context. We reviewed the results of diagnostic evaluations of all CSF samples analyzed for localization of a hematologic malignancy between 2001 and 2004 at our center. A total of 1,054 samples from 219 patients were available for analysis. Sixty patients had a CSF localization diagnosed by positive flow cytometry, cytomorphology, or both. The first sample was positive by flow cytometry in 44 (73%) patients, by cytomorphology in 19 (32%). Four first samples were positive by cytomorphology but negative by flow cytometry. Patients with positive cytomorphology had more frequent clinical symptomatology (95% vs 58%) and CSF pleocytosis (84% vs 25%), and tended to a poorer progression-free survival than patients with positive flow cytometry only. OR for CNS localization in case of CSF pleocytosis was 10.1 (95% CI 4.9 to 20.8); OR for CNS localization in case of elevated protein content was 2.9 (95% CI 1.5 to 5.4). Nevertheless, 26 of 137 (19%) patients with normal cell count and protein concentration had a CNS localization. The diagnostic value of flow cytometry is more than twice that of cytomorphology. However, cytomorphologic examination of the CSF has additional diagnostic and possibly prognostic value, and should still be performed in conjunction with flow cytometry.
    Neurology 06/2007; 68(20):1674-9. · 8.30 Impact Factor
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    ABSTRACT: Establishing the presence of paraneoplastic antibodies is important in identifying an often severe neurological syndrome as paraneoplastic and hence directing the search for an underlying neoplasm. A paraneoplastic neurological syndrome was diagnosed in 3 patients. The first was a 64-year-old woman in whom paraneoplastic encephalomyelitis was diagnosed. The diagnosis was strongly supported by a high titre of serum anti-Hu antibodies, despite three negative biopsies from a mediastinal mass. The patient died of a non-convulsive status epilepticus; autopsy revealed not only paraneoplastic encephalomyelitis but also small-cell lung cancer. The second patient was a 55-year-old woman with metastatic breast cancer. After a three-year period of progressive neurological deterioration, a high titre of anti-CV2/CRMP5 antibodies was detected, on the basis of which the clinical syndrome was diagnosed as paraneoplastic. She received immunotherapy and her condition stabilised. The third patient, a 41-year-old man, presented with severe limbic encephalitis. Biopsy from a paraaortic mass was positive for undifferentiated carcinoma. The patient had a high titre ofanti-Ma2 antibodies and was subsequently tested positive for serum alpha-foetoprotein (AFP) and beta-human-chorionic gonadotrophin (bta-HCG). During chemotherapy for a non seminoma testicular cancer, the limbic encephalitis improved both clinically and radiologically, but the patient died as a result of the toxicity of the treatment.
    Nederlands tijdschrift voor geneeskunde 05/2007; 151(15):874-80.
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    ABSTRACT: Corticosteroids can induce hypertension and inhibit collagen synthesis in the blood vessel wall. Deficiencies in collagen have been found in intracranial aneurysms. Therefore use of corticosteroids could be a risk factor for intracranial aneurysms and aneurysmal subarachnoid haemorrhage (SAH). We investigated the relationship between the systemic use of corticosteroids in the past and the occurrence of aneurysmal SAH. We compared the systemic use of corticosteroids (oral or intravenous) in the past between a consecutive series of 1158 patients with aneurysmal SAH and a control group consisting of 1019 patients diagnosed with a primary central nervous system (CNS) tumour. We discriminated between definite use of corticosteroids defined as use mentioned in the medical record and possible use defined as note in the medical record of a disease that may be treated with corticosteroids. We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI) and adjusted for age and sex by means of logistic regression analyses. Twenty (1.7%, 95% CI 1.1-2.7) of the SAH patients and eight (0.8%, 95% CI 0.3-1.5) of the controls had used systemic corticosteroids (OR: 2.22; 95% CI 0.97-5.05; p-value 0.058; adjusted OR 2.23; 95 % CI 0.97-5.15; p-value 0.059). For definite plus possible use the OR was 1.67 (95% CI 1.09-2.54; p-value 0.016) and the adjusted OR 1.52 (95% CI 0.99-2.33; p-value 0.055). Patients with aneurysmal SAH more often have used systemic corticosteroids in the past than controls. This may suggest that the use of corticosteroids is a risk factor for aneurysmal SAH.
    Journal of Neurology 05/2006; 253(4):496-9. · 3.58 Impact Factor
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    Neuro-Oncology. 01/2006; 8(4):452-453.
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    ABSTRACT: We compared the value of changes in proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and (1)H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of > or =20% compared to the baseline value was considered as indicative for progression on (1)H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant (1)H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on (1)H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on (1)H-MRSI. Our data do not show convincing evidence that (1)H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of (1)H-MRSI changes.
    Neuroradiology 12/2005; 47(12):887-91. · 2.70 Impact Factor
  • J E C Bromberg, T J Postma
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    ABSTRACT: There are new scientific data concerning the treatment of patients with glioblastoma multiforme with concomitant and adjuvant temozolomide following surgery and radiotherapy. Patients have an improved survival rate, especially if they also have a methylated promoter of the methylguanine-DNA-methyltransferase (MGMT) gene. It is advisable to consider treating young patients with primary glioblastoma multiforme who are in good condition with concomitant and adjuvant temozolomide. Efficacy of temozolomide in recurrent glioblastoma multiforme is limited.
    Nederlands tijdschrift voor geneeskunde 07/2005; 149(25):1376-8.
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    ABSTRACT: To evaluate the influence of radiation volume and other risk factors for the development of delayed radiation toxicity in patients treated for low-grade glioma, a retrospective analysis of 41 adult patients treated with focal or whole brain radiotherapy (WBRT) was performed. For all patients CT and MRI scans were revised to quantify brain atrophy and white matter lesions. Medical data were reviewed concerning baseline and tumor characteristics, treatment, survival, signs and symptoms of clinical encephalopathy and cardiovascular risk factors. In patients treated with WBRT an increased risk was found for brain atrophy (RR 3.1), white matter lesions (RR 3.8) and clinical encephalopathy (RR 4.2). An increased risk of atrophy (RR 2.2) and white matter lesions (RR 2.9) was also found in patients aged over 40 years. Furthermore, brain atrophy and white matter lesions were more severe in patients treated with WBRT and in older patients. In conclusion, both the incidence and the severity of abnormalities is greater in patients treated with WBRT and in older patients.
    Journal of Neuro-Oncology 03/2004; 66(3):333-9. · 3.12 Impact Factor
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    ABSTRACT: To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All patients were in complete remission after combined modality treatment with IV and intrathecal high-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT). An extensive neuropsychological assessment, including QOL measures, was conducted in 19 patients with PCNSL. The results were compared with matched control subjects with systemic hematologic malignancies treated with systemic chemotherapy or non-CNS radiotherapy. In addition, a neuroradiologic evaluation was carried out in 18 patients with PCNSL. Cognitive impairment was found in 12 patients with PCNSL (63%) despite a complete tumor response. Four patients (21%) showed severe cognitive deficits, and the percentage of impaired test indices correlated with age. In comparison, only two control subjects (11%) showed cognitive dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in contrast to 81% of the control subjects, resumed work. White matter abnormalities were observed in 14 patients with PCNSL, and 14 had cortical atrophy. Cortical atrophy correlated with cognitive functioning, age, and Karnofsky performance score. Group differences in cognitive status and QOL could not be explained by anxiety, depression, or fatigue. Combined modality treatment for primary CNS lymphoma is associated with cognitive impairment even in patients aged <60 years.
    Neurology 02/2004; 62(4):544-7. · 8.30 Impact Factor
  • J E C Bromberg, M D Siemers, M J B Taphoorn
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    ABSTRACT: The authors report clinical and radiologic characteristics and ultimate diagnosis in 12 patients with a regressing cerebral mass lesion. Primary CNS lymphoma (PCNL) was found in only half of the patients with such a lesion. In patients showing a complete resolution of the enhancing lesion the probability of finding a PCNL is smaller and survival is longer.
    Neurology 10/2002; 59(5):762-4. · 8.30 Impact Factor
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    ABSTRACT: Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%) without prior radiotherapy. White matter abnormalities were observed in six patients, all of whom were treated with prior radiotherapy. These radiologic cerebral abnormalities correlated with cognitive performance.
    Neurology 08/2002; 59(1):121-3. · 8.30 Impact Factor
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    ABSTRACT: A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans were revised by a neurologist and a radiologist in conference. White matter abnormalities before and after radiotherapy on the last scan before recurrence were quantified according to a semi-quantitative scale. All available medical records were retrieved and reviewed with respect to demographic and tumor-related variables, treatment modalities, disease-free and overall survival and clinical symptoms and signs of encephalopathy. CT and MRI scans showed severe white matter lesions in 75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent of patients presented with new clinical signs of cognitive impairment a median of 14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of white matter lesions appeared greater in patients aged >60 (RR 1.2, 95% CI = 0.8-2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8-2.1) and in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0-2.1). In conclusion, the risk of white matter lesions and clinical symptoms and signs of encephalopathy is high in patients treated by radiotherapy for PCNL. The risk appears to be greatest in older patients, patients with multifocal tumor and in those with prior white matter lesions on CT or MRI.
    Journal of Neuro-Oncology 04/2001; 52(1):73-80. · 3.12 Impact Factor

Publication Stats

417 Citations
91.63 Total Impact Points

Institutions

  • 2009–2012
    • Erasmus Universiteit Rotterdam
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
  • 2004–2009
    • Erasmus MC
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
  • 2002–2005
    • University Medical Center Utrecht
      • Department of Neurology
      Utrecht, Provincie Utrecht, Netherlands