Birgit Flechl

Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO)

BACKGROUND Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers. PATIENTS AND METHODS Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed. All patients were treated with standard first-line therapy. The primary end points were overall survival (OS) and time to progression (TTP). IDH1-R132H mutation status was analyzed using immunohistochemistry, and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction. RESULTS We included 70 patients (36 men and 34 women) with a median age of 33 years. IDH1-R132H mutations were detected in 22 (39.3%) of 56 cases and MGMT promoter methylation in 33 (61.1%) of 54 cases with available tissue samples. In patients with wild-type IDH, median TTP was 8.2 months and median OS was 24 months, compared with 18 months and 44 months, respectively, observed in patients with mutated IDH. Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS. Of note, the social and economical situation of the young patients with GBM was alarming, because only 17% succeeded in staying employed after receiving the diagnosis. CONCLUSIONS We found a high frequency of IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age. The social and economic coverage of patients with glioma remains an unsolved socio-ethical problem.

Sorafenib for patients with pretreated recurrent or progressive high-grade glioma: a retrospective, single-institution study.

Therapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9–4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4–4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9–8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1–16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk–benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.

Case Report: Pregnancy in a patient with recurrent glioblastoma.

We report the case of a woman with relapsed glioblastoma multiforme (GBM) who recently gave birth. She announced her pregnancy shortly after the sixth cycle of a dense regimen of temozolomide, prescribed for treating the first recurrence of glioblastoma. Three years ago, in April 2008, she had undergone gross total resection of a glioblastoma multiforme in the postcentral region of the right hemisphere and had subsequently received treatment according to the actual standard therapy consisting of radiotherapy up to 60 Gy with concomitant and adjuvant temozolomide. The complete amount of temozolomide given before this pregnancy was 20.9 mg/m 2. Nevertheless, she delivered a 1890 g child by caesarean section in the 32/6 week of pregnancy. The child showed no anomalies and is developing normally under close surveillance by paediatricians.

Assessment of improved organ at risk sparing for meningioma: light ion beam therapy as boost versus sole treatment option.

PURPOSE To compare photons, protons and carbon ions and their combinations for treatment of atypical and anaplastical skull base meningioma. MATERIAL AND METHODS Two planning target volumes (PTVinitial/PTVboost) were delineated for 10 patients (prescribed doses 50 Gy(RBE) and 10 Gy(RBE)). Plans for intensity modulated photon (IMXT), proton (IMPT) and carbon ion therapy ((12)C) were generated assuming a non-gantry scenario for particles. The following combinations were compared: IMXT+IMXT/IMPT/(12)C; IMPT+IMPT/(12)C; and (12)C+(12)C. Plan quality was evaluated by target conformity and homogeneity (CI, HI), V95%, D2% and D50% and dose-volume-histogram (DVH) parameters for organs-at-risk (OAR). If dose escalation was possible, it was performed until OAR tolerance levels were reached. RESULTS CI was worst for IMXT. HI<0.05±0.01 for (12)C was significantly better than for IMXT. For all treatment options dose escalation above 60 Gy(RBE) was possible for four patients, but impossible for six patients. Compared to IMXT+IMXT, ion beam therapy showed an improved sparing for most OARs, e.g. using protons and carbon ions D50% was reduced by more than 50% for the ipsilateral eye and the brainstem. CONCLUSION Highly conformal IMPT and (12)C plans could be generated with a non-gantry scenario. Improved OAR sparing favors both sole (12)C and/or IMPT plans.

The End-of-Life in patients with glioma and their families

Patients with glioblastoma multiforme (GBM) are confronted with a very serious disease and suffer sooner or later from various physical, psychic, cognitive, and behavioral symptoms. This is a big challenge, not just for the patients, even their (caring) family members are forced to deal with this new life-changing situation. Studies investigate symptoms and circumstances of GBM patients during their End-of-Life phase. It is out of discussion, that patients with GBM and their family members should be prepared for the inevitable End-of-Life phase very early in the disease, however, presently there are neither existing guidelines for treating physicians, nor educational programs for caring family members available.

Clinical outcome of GBM long-term survivors.

e12507 Background: An increasing number of patients with Glioblastoma mulitforme (GBM) are alive up to three years after diagnosis (long-term survivors). Hence there is an urgent need for data about their clinical outcome and quality of life to optimize the medical management and function of patients. METHODS In this cross sectional study we studied 16 GBM long-term survivors treated at the outpatient clinic of the Medical University Hospital Vienna. The patients have been treated there since their diagnosis. We assessed patients clinical outcome to get global information about the circumstances under which they live. RESULTS We assessed 8 female and 8 male GBM long-term survivors with a median age of 52 years (71-30). 14 of them lived together with their partner (and children) while two lived single. The mean of the summary-score of the Neuro Cog-Fx, a computerized instrument for neurocognitive assessment of patients with neurological diseases, was 88 and ranged from 70 to 111, whereas results from 61-79 are defined conspicuous, 80-89 borderline and results up to 90 normal. The global health score ranged from 17% to 100% with a mean of 68%. Drowsiness, weakness in both legs and a headache were the most stated physical problems. The Independent Activities of Daily Living - Score ranged from 0-8 points; mean was 7 points and Barthel Index resulted in 35-100 with a mean of 92 points. Six patients showed impairment in their manual dexterity, one patient in their mobility. Three patients showed conspicuous depression scores, two had conspicuous anxiety results. Furthermore, future uncertainty was stated in 12 patients. CONCLUSIONS GBM long-term survivors show moderate impairment in their cognitive functions and often suffer from physical problems. However, the majority of the GBM long-term survivors is able to manage their activities of daily living independently. Nevertheless, global health and future prospects remain poor.