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Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5-82.5) and median Karnofsky performance status (KPS) was 60 (range, 40-80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2-6.2), and median overall survival was 8.2 months (95%CI: 0.6-15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL. [ABSTRACT FROM AUTHOR]

Purpose: The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and F-FDOPA uptake on PET in newly diagnosed gliomas. Methods: A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone F-FDOPA PET at an initial stage before surgery and histological diagnosis. F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Results: Patients with IDH mutation showed higher F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation ( p < 0.05). Conclusion: This study showed paradoxically higher F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation. [ABSTRACT FROM AUTHOR]

Patients with high-grade gliomas (HGG) and their caregivers have to confront a very aggressive disease that produces major lifestyle disruptions. There is an interest in studying the ability of patients and their caregivers to cope with the difficulties that affect quality of life (QoL). We examine, in a sample of patient-caregiver dyads in the specific context of newly diagnosed cases of HGG, whether the QoL of patients and caregivers is influenced by the coping processes they and their relatives use from a specific actor-partner interdependence model (APIM). This cross-sectional study involved 42 dyads with patients having recent diagnoses of HGG and assessed in the time-frame between diagnosis and treatment initiation. The self-reported data included QoL (Patient-Generated Index, EORTC QLQ-C30, and CareGiver Oncology QoL), emotional status, and coping strategies (BriefCope). The APIM was used to test the dyadic effects of coping strategies on QoL. Coping strategies, such as social support, avoidance, and problem solving, exhibited evidence of either an actor effect (degree to which the individual's coping strategies are associated with their own QoL) or partner effect (degree to which the individual's coping strategies are associated with the QoL of the other member of the dyad) for patients or caregivers. For positive-thinking coping strategies, actor and partner effect were not observed. This study emphasizes that the QoL for patients and their caregivers was directly related to the coping strategies they used. This finding suggests that targeted interventions should be offered to help patients and their relatives to implement more effective coping strategies. [ABSTRACT FROM AUTHOR]

The prognosis of oncology patients admitted to the intensive care unit (ICU) is considered poor. Our objective was to analyze the characteristics and predictive factors of death in the ICU and functional outcome following ICU treatment for neuro-oncology patients. A retrospective study was conducted on all patients with primary brain tumor admitted to our institutional ICU for medical indications. Predictive impact on the risk of death in the ICU was analyzed as well as the functional status was evaluated prior and following ICU discharge. Seventy-one patients were admitted to the ICU. ICU admission indications were refractory seizures (41 %) and septic shock (17 %). On admission, 16 % had multi-organ failure. Ventilation was necessary for 41 % and catecholamines for 13 %. Twenty-two percent of patients died in the ICU. By multivariate analysis, predictive factors associated with an increased risk of ICU death were: non-neurological cause of admission [p = 0.045; odds ratio (OR) 5.405], multiple organ failure (p = 0.021; OR 8.027), respiratory failure (p = 0.006; OR 9.615), and hemodynamic failure (p = 0.008; OR 10.111). In contrast, tumor type (p = 0.678) and disease control status (p = 0.380) were not associated with an increased risk of ICU death. Among the 35 evaluable patients, 77 % presented with a stable or improved Karnofsky performance status following ICU hospitalization compared with the ongoing status before discharge. In patients with primary brain tumor admitted to the ICU, predictive factors of death appear to be similar to those described in non-oncology patients. ICU hospitalization is generally not associated with a subsequent decrease in the functional status. [ABSTRACT FROM AUTHOR]

Bevacizumab has demonstrated activity in patients with recurrent glioblastoma. However, the impact of prognostic factors associated with recurrent glioblastoma treated with cytotoxic agents has not been determined in patients treated with bevacizumab. To analyze the prognostic factors and clinical benefits of bevacizumab and irinotecan treatment in patients with recurrent glioblastoma. This monocentric study retrospectively analyzed all patients with recurrent glioblastoma who were treated with at least one cycle of bevacizumab and irinotecan at our institution from April 2007 to May 2010. Multivariate analysis was used to analyze prognostic factors for overall survival (OS) from the initiation of bevacizumab administration. Among the 100 patients that were identified (M/F: 65/35), the median age was 57.9 years (range: 18-76). Karnofsky Performance Status (KPS) was <70 in 44 patients and ≥70 in 56 patients; 83 % of the patients were on steroids. The median tumor area was 2012 mm. The median progression free survival was 3.9 months (CI 95 %: 3.4-4.3). The median OS was 6.5 months (CI 95 %: 5.6-7.4). Multivariate analysis revealed that OS was affected by KPS ( p = 0.024), but not by gender, age, steroid treatment, number of previous lines of treatment, tumor size, or time from initial diagnosis. KPS was improved in 30 patients, including 14/44 patients with an initial KPS <70. The median duration of maintained functional independence (KPS ≥70) was 3.75 months (CI 95 %: 2.9-4.6). The median OS from initial diagnosis was 18.9 months (CI 95 %: 17.5-20.3). In patients with recurrent glioblastoma treated with bevacizumab, KPS was revealed as the only factor to impact OS. The clinical benefits associated with this regimen appear valuable. A positive impact of bevacizumab administration on OS of patients with glioblastoma multiforme is suggested. [ABSTRACT FROM AUTHOR]

Despite treatment with the current standard-of-care therapies, patients with newly diagnosed glioblastoma multiforme (GBM) exhibit dismal prognoses. Bevacizumab has demonstrated activity in patients with recurrent GBM and phase 2 trials indicate that the combination of bevacizumab with standard-of-care therapy is feasible and active for patients with newly diagnosed GBM. Bevacizumab has been granted US approval for use as single-agent therapy for patients with progressive GBM following prior therapy, although it has not received approval for use in patients with GBM in Europe. Phase 3 studies have been initiated in patients with newly diagnosed GBM and are currently recruiting patients. We describe the protocol for the AVAglio phase 3 registration trial, which is designed to evaluate the efficacy and safety of combining bevacizumab with standard-of-care therapy in patients with newly diagnosed GBM. [ABSTRACT FROM AUTHOR]

Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5′-untranslated region (5′ UTR) of human AM mRNA. Reverse transcriptase–polymerase chain reaction of the 5′ UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an ∼65-bp deletion from the central region of the 5′ UTR, suggesting the presence of a secondary structure. The presence of a stem–loop structure was confirmed by probing the 5′ UTR with RNases with selectivity for single- or double-stranded RNA. We investigated the role of this stem–loop structure in expression of luciferase reporter gene in cultured cell lines. Reporter assays using a chimeric mRNA that combined luciferase and the 5′ UTR of AM mRNA demonstrated a dramatic decrease of the reporter activity owing to a decreased translation, whereas the deletion of the stem–loop structure localized between nt +31 and +95 from the cap site led to the recovery of activity. Gel migration shift assays using cytosolic extracts from mammalian cell lines demonstrate a specific binding of a cytosolic protein to riboprobes containing the 5′ UTR of AM but not to riboprobes either corresponding to other areas of the message or containing the 5′ UTR but lacking the region of secondary structure. Although we conclude that the 5′ UTR of the human AM mRNA can modulate the translation of AM mRNA in vivo, and that the predicted stem–loop structure is necessary for this inhibition, the functional consequences of the cis element-binding activity remain to be determined.Oncogene (2006) 25, 6510–6519. doi:10.1038/sj.onc.1209672; published online 22 May 2006 [ABSTRACT FROM AUTHOR]

Object. The aim of this study was to document the possible role of Gamma Knife radiosurgery, suitable for the treatment of deep and well limited tumors, in the management of pineal parenchymal tumors (PPT). Population and methods. We reviewed retrospectively a series of 13 patients with PPT treated by Gamma Knife radiosurgery during 16 procedures. Mean age was 31 (range 10 to 74). Eight patients had pineocytomas (61.5%), and 5 had pineoblastomas (38.5%). Radiosurgery was performed alone in 6 cases, after partial microsurgical resection in 3 cases, in association with chemotherapy in 3 cases and following conventional fractionated radiotherapy in 1 case. The marginal dose to these tumors ranged from 11 to 20 Gy (mean 15 Gy). Results. With a mean follow-up of 34 months (range 6 to 88), all tumors responded to treatment and disappeared or ceased growing. Two patients with pineoblastoma had tumor size progression out of the initial target requiring several radiosurgery procedures. At the end of the follow-up period, 10 out of 12 patients were alive. Two patients with pineoblastoma died because of carcinomatous meningitis or tumor size progression. We observed no mortality or major morbidity related to radiosurgery. Conclusion. This study confirms that radiosurgery can be an effective and safe primary treatment modality for patients with pineocytomas. It should have a role in multimodality therapy which includes microsurgical resection, fractionated radiotherapy and chemotherapy for the management of malignant pineal tumors. [ABSTRACT FROM AUTHOR]

The presence of telomerase activity in a glioma may be a predictor of its malignant potential. Activation of telomerase is regulated at the transcriptional level of the human telomerase reverse transcriptase (hTERT). Here, we evaluated whether the amount of hTERT mRNA provides a molecular marker of glioma malignancy that would have clinical utility. We used a real-time RT-PCR to assess the number of hTERT transcripts in primary tumour samples derived from 70 glioma patients. Results were standardised by quantifying the number of ABL transcripts as internal control and expressed as hTERT/ABL ratio. The percentage of patients with detectable hTERT mRNA markedly increased with enhanced malignancy: low-grade gliomas expressed hTERT in one out of 14 cases (7.1%), anaplastic gliomas in four out of 13 cases (30.8%) and glioblastoma multiforme (GBM) tumours in 30 out of 43 cases (69.8%). The mean hTERT/ABL ratio was significantly higher in GBMs than in non-GBMs. Subdividing hTERT/ABL ratios as low (< pr = 25%) and high (>25%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P=0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients. [ABSTRACT FROM AUTHOR]

Presents guidelines of the organizing committee Standards, Options and Recommendations for the management of adult patients with intracranial glioma. Incidence and risk factors for intracranial glioma; Histological, molecular biological and cytogenetical diagnosis of the patients; Treatments modalities of the disease.