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Biomedical subjects

K Hoang-Xuan

Publications and source records attributed to K Hoang-Xuan.

At least 19 recordsLinked to original sources
PubMed2006

MRI features of neurodegenerative Langerhans cell histiocytosis.

CNS complications of LCH include "space occupying" lesions corresponding to histiocytic granulomas and "neurodegenerative" presentation (ND-LCH) characterized by a progressive cerebellar ataxia. Studies analyzing specifically the MRI presentation of ND-LCH are scarce. We present here the MRIs of 13 patients registered as isolated ND-LCH. Posterior fossa was involved in 12 patients (92%), showing a symmetrical T2 hyperintensity of the cerebellar white matter areas in seven cases with a circumscribed T1 hyperintensity of the dentate nuclei in five cases, definite hyperintense T2 areas in the adjacent pontine tegmentum white matter in nine cases associated with a hyperintensity of the pontine pyramidal tracts in four cases. A cerebellar atrophy was noted in eight cases. The supratentorial region was involved in 11 patients, showing T2 hyperintense lesions in the cerebral white matter in eight cases and a discrete symmetrical T1 hyperintense signal in the globus pallidus in eight patients. A diffuse cortical atrophy was present in three cases and a marked focal atrophy of the corpus callosum in three cases. This series allows us to establish a not previously reported evocative semeiologic MR presentation to precisely orientate to the diagnosis of the pure neurodegenerative form of LCH.

Adolescent↗
PubMed2005

Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of carmustine (BCNU) in combination with temozolomide as first-line chemotherapy before and after radiotherapy (RT) in patients with inoperable, newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: Forty patients were treated with BCNU (150 mg/m2) on day 1 and temozolomide (110 mg/m2/day) on days 1 through 5 of each 42-day cycle for up to four cycles prior to conventional RT (2 Gy fractions to a total of 60 Gy). After RT, BCNU + temozolomide was administered for four additional cycles or until progression. The primary end point was response rate; secondary end points included progression-free survival (PFS); overall survival (OS) and safety. RESULTS: Sixty per cent of patients completed four cycles of neo-adjuvant BCNU + temozolomide. Objective response rate (intention-to-treat) was 42.5% (95% confidence interval 27% to 58%), including two (5%) complete and 15 (37.5%) partial responses. In the eligible population (n=37) the objective response rate was 46%. Nine (24%) patients had stable disease and 14 (35%) had progressive disease. Median PFS and OS were 7.4 and 12.7 months, respectively. Age was the only significant prognostic factor and tumor location (lobar versus multifocal versus corpus callosum) showed a trend. Grade 3-4 toxicities included thrombocytopenia (n=11) and neutropenia (n=7) for both pre- and post-RT chemotherapy. Four patients required platelet transfusions. No patient discontinued treatment because of toxicity. CONCLUSIONS: The combination of BCNU plus temozolomide as neo-adjuvant therapy in inoperable GBM exhibited promising activity with a good safety profile and warrants further evaluation.

Adult↗
PubMed2005

EGFR tyrosine kinase domain mutations in human gliomas.

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor effective in patients with lung cancer with mutations in exons 19 and 21 of the EGFR tyrosine kinase domain. In this study, the authors tested the presence of such mutations in 95 gliomas including glioblastomas, anaplastic oligodendrogliomas, and low-grade gliomas. No mutation was found, which suggests that the biology of EGFR in gliomas is different from lung cancer and that this may be a factor in the resistance of glioblastomas to gefitinib.

Astrocytoma↗
PubMed2005

The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common phenomenon, often resulting in serious limitations in daily functioning and compromised quality of life. Currently available toxicity grading systems typically use a combination of clinical and paraclinical parameters and relies on the judgment of clinicians and/or nurses. However, because many of the symptoms of CIPN are subjective in nature, it is only logical that an assessment of CIPN be based, at least in part, on patient self-report data. We report on the development of a patient self-report questionnaire, the CIPN20, intended to supplement the core quality of life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC). Following EORTC guidelines, relevant CIPN-related issues were identified from a literature survey and interviews with health professionals (n=15) and patients (n=112). The resulting 20-item questionnaire was pre-tested in three languages and four countries and is currently being examined in a large, international clinical trial. The EORTC CIPN20 should provide valuable information on CIPN-related symptoms and functional limitations of patients exposed to potentially neurotoxic chemotherapeutic and/or neuroprotective agents.

Adult↗
PubMed2005

[Molecular biology of oligodendroglial tumors].

Oligodendrogliomas have been the focus of considerable interest over the last decade, ever since they were recognized as chemosensitive tumors. However, the histological diagnosis remains highly controversial and unsatisfactory. Meanwhile, our understanding of glioma oncogenesis improved greatly. Gliomas are the consequence of specific genetic or epigenetic alterations - activations of oncogenes and inactivation of tumor suppressor genes - resulting in the disruption of critical cellular pathways and leading to phenotypic changes. Such genetic information complements the existing WHO morphological classification and, more importantly, provides additional prognostic markers. Indeed, 1p/19q deletion has been correlated with chemosensitivity in oligodendrogliomas, and is becoming more and more widely used in clinical practice. There is little doubt that emerging techniques, such as CGH-array and gene profiling will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.

Brain Neoplasms↗
PubMed2005

[Primary central nervous system lymphoma presenting with central neurogenic hyperventilation. A case report and review of the literature].

INTRODUCTION: Central neurogenic hyperventilation (CNH) in an awake patient is a rare entity. OBSERVATION: We report here a 54-year-old patient who developed central neurogenic hyperventilation as the initial presentation of a primary central nervous system lymphoma located in the brainstem. CONCLUSION: The patient's hyperventilation resolved completely with chemotherapy for primary CNS lymphoma. Most of the cases reported in the literature are related to a diffuse tumor of the brainstem with an intriguing overrepresentation of primary CNS lymphoma. The pathogenesis of CNH is discussed.

Brain Stem Neoplasms↗
PubMed2005

Olig2 expression, GFAP, p53 and 1p loss analysis contribute to glioma subclassification.

The expression of Olig2, a basic helix-loop-helix (bHLH) transcription factor involved in oligodendroglial specification, was investigated by immunohistochemistry in a series of 146 tumours and control samples. Olig2 expression was restricted to glial tumours and nontumoral oligodendrocytes. It was higher in oligodendrogliomas as compared to astrocytomas and oligoastrocytomas, and in grade III as compared to grade II tumours. Olig 2 was absent or weakly expressed in glioblastoma (GBM), whereas strong expression was found in the oligodendroglial foci of GBM with oligodendroglial component (GBMO). Double labelling was performed on a subset of the most typical tumours, according to the WHO classification. It showed a mutual exclusion, at cell level, of Olig2 and GFAP expression. In pure oligodendrogliomas, tumour cells were Olig2+/GFAP-. In contrast, two main tumour populations, Olig2+/GFAP- and Olig2-/GFAP+, were found in both oligoastrocytomas and astrocytomas. Based on these data from selected samples, two separate entities can be established, corresponding to 'pure oligodendrogliomas' and 'astrocytomas and oligoastrocytomas'. The relevance of this subdivision is further supported by the association with 1p loss and a trend to better survival for pure oligodendrogliomas and with p53 expression and a trend to shorter survival for astrocytomas and oligoastrocytomas. Combined testing of Olig2, 1p status, GFAP and p53 expression may therefore be helpful in refining current classification and providing more homogeneous sets of gliomas for clinical studies.

Basic Helix-Loop-Helix Proteins↗
PubMed2004

Correlations between molecular profile and radiologic pattern in oligodendroglial tumors.

OBJECTIVE: To investigate possible correlations between tumor location and genetic alterations in a series of oligodendrogliomas. METHODS: A series of 158 consecutive oligodendrogliomas were retrospectively reviewed. In each case, the radiologic picture and the chromosome 1p (chr 1p) status of the tumor detected by the loss of heterozygosity technique were analyzed. Correlation between tumor location and molecular profile was made by chi2 tests. RESULTS: Eighty-eight of the 158 patients had low-grade oligodendrogliomas, and 70 had anaplastic oligodendrogliomas. Overall, oligodendrogliomas with chr 1p loss were located preferentially in the anterior part of the brain, whereas tumors with intact chr 1p affected mainly the posterior part of the brain (p = 0.0038). In terms of lobar involvement, a preferential location of oligodendrogliomas with chr 1p loss was found in the frontal lobes as compared with the temporal, parietal, and occipital tumors (p < 0.01). CONCLUSION: There is a significant correlation between loss of heterozygosity on chromosome 1p and tumor location in oligodendrogliomas, suggesting that subtypes of oligodendrogliomas could derive from site-specific precursors.

Adult↗
PubMed2004

Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions.

PURPOSE: To determine the response rate of low-grade oligodendroglial tumors (LGOT) to temozolomide (TMZ) as initial treatment and to evaluate the predictive value of chromosome 1p deletion on the radiologic response. PATIENTS AND METHODS: Adult patients with pathologically proven LGOT with progressive disease on magnetic resonance imaging (MRI) were eligible for the study. TMZ was administered at the starting dose of 200 mg/m2/d for 5 days, repeated every 28 days. Response was evaluated clinically and by central review of MRIs. Chromosome 1p and 19q deletions were detected by the loss of heterozygosity technique. RESULTS: Sixty consecutive patients were included in the study. At the time of analysis, the median number of TMZ cycles delivered was 11. Clinically, 51% of patients improved, particularly those with uncontrolled epilepsy. The objective radiologic response rate was 31% (17% partial response and 14% minor response), whereas 61% of patients had stable disease and 8% experienced disease progression. The median time to maximum tumor response was 12 months (range, 5 to 20 months). Myelosuppression was the most frequent side effect, with grade 3 to 4 toxicity in 8% of patients. Loss of chromosome 1p was associated with objective tumor response (P < .004). CONCLUSION: TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.

Adult↗
PubMed2004

Initial chemotherapy in gliomatosis cerebri.

BACKGROUND: Because of the diffuse nature of gliomatosis cerebri (GC), surgery is not suitable, and large field radiotherapy carries the risk of severe toxicity. In this setting, initial chemotherapy warrants further investigation. METHODS: The authors treated 63 consecutive patients with GC with initial chemotherapy consisting of either PCV (procarbazine, 60 mg/m2 on days 8 to 21; CCNU, 110 mg/m2 on day 1; and vincristine, 1.4 mg/m2 on days 8 and 29) or temozolomide (TMZ; 150 to 200 mg/m2 for 5 days every 4 weeks). There were 40 men and 23 women, with a median age of 48 years (range, 17 to 74 years) and a median Karnofsky performance status of 90 (range, 50 to 100). GC was initially present at diagnosis in 49 patients (primary GC), whereas 14 patients with a circumscribed glioma at onset developed secondary GC after a median follow-up period of 5.11 years. GC was classified based on the predominant tumor cells as astrocytic, oligodendroglial, or mixed GC. RESULTS: Seventeen patients received 1 to 6 cycles (median, 5) of PCV, and 46 received 2 to 24 courses (median, 13) of TMZ. Grade 3 to 4 hematologic toxicity was seen in 4 of 17 (23.5%) patients treated with PCV and in 4 of 46 (8.6%) of those treated with TMZ. Clinical objective responses were observed in 21 of 63 (33%) patients, and radiologic responses were seen in 16 of 62 (26%), with no significant difference between the two regimens. For all patients combined, the median progression-free survival (PFS) and overall survival (OS) were 16 months and 29 months, respectively. Regardless of the chemotherapeutic regimen, oligodendroglial GC had a better prognosis than astrocytic and oligoastrocytic GC in terms of PFS (p < 0.02) and OS (p < 0.0001). CONCLUSION: Initial chemotherapy is useful for some patients with gliomatosis cerebri. Temozolomide is well tolerated and appears to be a valuable alternative to procarbazine-CCNU-vincristine, especially for those with slow-growing, low-grade GC.

Adolescent↗
PubMed2004

Retinoic acid therapy in "degenerative-like" neuro-langerhans cell histiocytosis: a prospective pilot study.

BACKGROUND: Degenerative-like neuro-Langerhans cell histiocytosis (DN-LCH) is a rare complication of LCH marked by progressive cerebellar ataxia. No treatment has so far been shown to slow this progression. PROCEDURE: All-trans retinoic acid (ATRA) was administered orally at a dose of 45 mg/m(2) daily for 6 weeks and then 2 weeks every month for 1 year. The endpoints were clinical status at 1 year (assessed with rating scales for ataxia and disability), adverse effects, and changes in neurological abnormalities on MRI. RESULTS: Ten patients were studied. The treatment was well tolerated. All the patients were clinically stable at the end of the study. No MRI changes were noted. CONCLUSIONS: DN-LCH appeared to be stable during ATRA therapy, but further studies are required to appreciate the possible long-term benefits of ATRA.

Adolescent↗
PubMed2003

Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group.

PURPOSE: To assess the efficacy and toxicity of chemotherapy alone in patients older than 60 years with primary CNS lymphoma. PATIENTS AND METHODS: Fifty patients with a median age of 72 years and a median Karnofsky performance score (KPS) of 50 were eligible for this multicenter phase II study. The protocol consisted of high-dose methotrexate (MTX), lomustine, procarbazine, methylprednisolone, and intrathecal chemotherapy with MTX and cytarabine. The patients received one induction cycle; if objective response was achieved, five additional maintenance cycles were administered every 6 weeks. The median follow-up of patients was 3 years. RESULTS: Twenty four patients (48%) achieved an objective response (compete response [CR], 42%; partial response, 6%), with a median duration of CR of 27 months (range, 3 to 47+ months). Overall median survival time was 14.3 months, and 1-year progression-free survival was 40% (95% confidence interval [CI], 26% to 53%). Myelosuppression was the most frequent side effect, with grade 3 to 4 neutropenia in 19% of patients. One patient died during chemotherapy, as a result of pulmonary embolism. Most patients improved or preserved their cognitive functions (47% and 45% of the patients, respectively) and KPS (36% and 52% of the patients, respectively) until relapse, whereas cognitive and KPS decline attributed to delayed treatment neurotoxicity occurred in 8% and 12% patients, respectively. CONCLUSION: In the elderly, this chemotherapy regimen compares favorably with radiotherapy (RT) alone and reduces considerably the risk of delayed neurotoxicity associated with combined chemoradiotherapy. Chemotherapy alone is an appropriate strategy in older patients to delay or avoid RT.

Age Factors↗
PubMed2003

Telomerase reactivation in malignant gliomas and loss of heterozygosity on 10p15.1.

An inhibitor of telomerase activity maps to chromosome 10p15.1. A series of 51 high-grade gliomas was analyzed for loss of heterozygosity (LOH) on chromosome 10 and for telomerase activity. In univariate analysis, LOH10p (59%) and LOH10q (61%) were associated with telomerase activity (55%; p < 0.0001 and p = 0.0006). In multivariate analysis, only LOH10p remained statistically related to telomerase activity, suggesting that the telomerase repressor gene located on 10p15.1 is inactivated in high-grade gliomas.

Chromosome Mapping↗
PubMed2002

Intravascular malignant lymphomatosis.

Intravascular malignant lymphomatosis is a rare and probably often overlooked disease characterised by massive intravascular proliferation of lymphoid cells, usually with a poor prognosis. CT and MRI appearances are nonspecific; the most suggestive finding being both asymmetrical, bilateral, contrast enhancing high-signal areas on T2 weighting and infarct-like lesions of the cortex and basal ganglia. We report two patients with previously unreported dural and spinal cord involvement.

Adult↗
PubMed2001

Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression.

OBJECTIVE: To identify different genetic molecular profiles in oligodendrogliomas and to evaluate their prognostic significance. METHODS: The main genetic alterations reported in glial tumors were investigated in 26 oligodendrogliomas (10 World Health Organization grade II and 16 World Health Organization grade III). Correlation between identified molecular changes and pathologic grade or clinical course was subsequently analyzed using univariate and multivariate statistical analyses. RESULTS: Loss of heterozygosity (LOH) on chromosome 1p, 19q, and 10; P16/CDKN2A homozygous deletion; EGFR (epidermal growth factor receptor) amplification; and TP53 and PTEN mutations were observed in 14 (54%), 15 (58%), 9 (35%), 7 (27%), 5 (19%), 1 (4%), and 0 cases. LOH 1p and 19q were tightly associated (p < 0.0001). A mutual exclusion was found between LOH 1p/19q and EGFR amplification (p = 0.01), P16/CDKN2A deletions (p = 0.001), or LOH on 10q (p = 0.03), suggesting the existence of distinct genetic subsets in oligodendrogliomas. On univariate analysis, age <50 years (p = 0.002) and LOH 1p (p = 0.01) were associated with a longer progression-free survival (PFS) whereas LOH 10q (p = 0.03) and EGFR amplification (p = 0.007) were associated with a worse PFS. In multivariate analyses, age <50 years (p = 0.001) and LOH 1p (p = 0.006) remained independent predictive factors for PFS. CONCLUSION: These results provide evidence for two alternative molecular pathways of progression in oligodendrogliomas. The first one is associated with loss of 1p and 19q and the second one with P16/CDKN2A deletion, 10q loss, and EGFR amplification. The findings confirm the value of loss of 1p as predictor of longer progression-free survival; in addition, the study demonstrates the unfavorable impact of 10q loss and EGFR amplification on the prognosis.

Adult↗