Supervision of low-grade gliomas with multiparametric MR imaging: research of radiologic indicators of malignancy transformation

articleWe assessed the contribution of diffusion, perfusion and spectroscopy imaging for the diagnosis and follow-up of intraaxial tumors, suspected to be grade II gliomas. Twenty-four patients were included from April 2005 to July 2006, 17 initially and seven during their follow-up. The diagnosis was reconsidered in a first group of six patients: a high-grade tumor was suspected and confirmed in five. These patients presented a lipid peak; the perfusion results and the CHO/Cr and CHO/NAA ratios were not pathological. The second group included patients with grade II gliomas: these 18 patients had a radiographic work-up, initially, then at three months and every six months. For this group, no evidence of a change of grade were observed. Abnormal findings were noted in seven patients: among these patients, one developed radiographic progression, one other had radiographic progression associated with a spectroscopy lipid peak; only spectroscopy changes were noted in the third patient; the last patient had radiographic progression with perfusion and spectroscopy abnormalities; these four patients were treated. These observations suggest that diffusion, perfusion and spectroscopy can provide supplementary information for diagnosis and follow-up of glial tumors. The presence of a lipid peak is of particular value. The limitations of this work must also be taken into consideration: the follow-up was too short for slow-growing gliomas; the population was small and patients may have undergone surgery during the study, leading to structural modifications which may have compromised comparisons. This work should be continued with new examinations every six months and inclusion of new patients

Management of glioblastoma : comparison of clinical practices and cost-effectiveness in two cohorts of patients (2008 versus 2004) diagnosed in a French university hospital

What is known and objective Therapeutic options for the management of glioblastoma (GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. Methods A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. Results One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54 388 € in group 1 and 71 148 € in group 2 (P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54 355 € per life-year gained. What is new and conclusion As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs

Current trends in the management of glioblastoma in a French University Hospital and associated direct costs

What is new and objectives Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma (GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. Methods A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. Results Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5-ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). What is new and conclusion This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours

Bevacizumab/Irinotecan. Un nouveau traitement actif dans les gliomes de haut grade récidivants : résultats préliminaires d'une étude multicentrique de l'Anocef

INTRODUCTION: Les chimiothérapies de seconde ligne dans les gliomes de haut grade récidivants sont décevantes. Des résultats spectaculaires avec la combinaison originale d'un antiangiogénique (bevacizumab, anticorps monoclonal anti-VEGF) et d'une chimiothérapie par irinotecan ont été récemment rapportés dans des gliomes malins récidivants dans un essai monocentrique. L'objectif de cette étude était de rapporter l'expérience de l'Association des neuro-oncologues d'expression française (Anocef) avec cette combinaison dans cette indication. METHOD: Huit équipes ont colligé leurs résultats obtenus avec l'association bevacizumab–irinotecan administrée conformément au protocole précédemment publié. Ce traitement a été délivré à titre compassionnel chez des patients non sélectionnés porteurs d'une tumeur gliale de haut grade récidivante (grade III et IV OMS). Une analyse rétrospective de la réponse radiologique précoce à deux mois selon les critères de Macdonald a été effectuée ainsi qu'une évaluation de la toxicité du traitement. RESULTS: Entre 2006 et 2007, 77 patients ont été traités (âge médian : 52ans) pour un gliome malin récidivant (49 grade IV, 28 grade III). À deux mois, on observait 36 % de réponse objective (54 % grade III, 27 % grade IV), 39 % de stabilisation, 13 % de progression (12 % non-évaluables). Une amélioration clinique fut observée chez 49 % des patients. Les effets secondaires rencontrés étaient une hémorragie intratumorale dans cinq cas dont trois spontanément résolutives, des accidents thrombœmboliques : phlébite dans quatre cas, embolie pulmonaire dans deux cas, infarctus du myocarde dans un cas, une hématotoxicté de grade III-IV dans deux cas ; enfin un cas de leucoencéphalopathie regressive. CONCLUSION: Cette étude rétrospective multicentrique confirme les résultats prometteurs et la rapidité d'action de cette thérapeutique. Les complications justifient une surveillance attentive du traitement et un strict respect des contre-indications cardiovasculaires. RATIONALE: Second-line chemotherapy is disappointing in recurrent high-grade gliomas. Dramatic responses in recurrent high-grade gliomas have been reported in a recent monocentric trial with a novel association combining bevacizumab (anti-VEGF monoclonal antibody agent) and irinitecan. OBJECTIVE: To report the experience of the ANOCEF group (French speaking neuro-oncology association) using the bevacizumab-irinotecan combination in recurrent high-grade gliomas. METHODS: Eight centers were involved in this retrospective multicenter study. Bevacizumab-irinotecan was delivered as previously described in a compassional setting to non-selected patients suffering from a high-grade glioma (WHO grade III and IV). Response rate at two months of the onset of the treatment was analyzed using the Macdonald criteria. The toxicity profile of the treatment was also investigated. RESULTS: From 2006 to 2007, 77 patients were treated (median age: 52 years; median Karnofsky score: 70) for a recurrent high-grade glioma (49 grade IV, 28 grade III). At two months, the response rates were objective response=36% (54% in grade III and 27% in grade IV); stable disease=39%; progressive disease=13%; patients not evaluable because of a rapid fatal clinical deterioration=12%. Improvement was noted in 49% of patients. Among the main toxicities, we noted; intratumoral hemorrage (n=5 with spontaneous regression in three) and thromboembolic complications including venous thrombophlebitis (n=4), pulmonary embolism (n=2), myocardial infarction (n=1), grade III-IV hematotoxicity (n=2), reversible leukoencephalopathy (n=1). CONCLUSION: This retrospective multicenter study adds further arguments in favor of the promising results of this new combination and its potential rapidity of action in recurrent high-grade gliomas. Antiangiogenic agents expose the patients to a well-known risk of thromboembolic and hemorragic complications, necessitating careful follow-up and patient selection in light of the cardiovascular contraindications