Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma.

PURPOSE: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. METHODS: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. RESULTS: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5-30) months in arm A and 6.5 (0.3-51.5) months in arm B. The median PFS was 2.8 months (95% CI 0-8.7) in arm A and 2.1 months (95% CI 0-11.8) in arm B. The median OS was 5.0 (0.8-30) months (95% CI 0-24.1) in arm A and 6.5 (0.3-51.5) months (95% CI 0-32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). CONCLUSIONS: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.

Seizure and status epilepticus in chronic subdural hematoma.

BACKGROUND: Acute symptomatic seizure (ASz) and status epilepticus (SE) are serious conditions associated with poor quality of life, with unfavorable psychosocial and functional outcome. Chronic subdural hematoma (cSDH) is a common neurosurgical disease related to those complications; therefore, we aimed to evaluate incidence, predictors of ASz/SE, and outcome in this cohort. METHODS: We retrospectively analyzed patient diagnosed cSDH between 2010 and 2017. Beside their incidence of ASz/SE, patient characteristics, symptoms at admission, comorbidities, and all previously published relevant parameters were assessed. Recurrence rate and functional outcome were analyzed at hospital discharge and 90-day follow-up. RESULTS: A total of 375 patients were included; incidence of ASz was 15.2% and of SE, 1.9%. In the univariate analysis, drainage insertion (P =  0.004; OR = 0.3) was a significant negative predictor for ASz/SE and multivariate analysis, including all significant parameters, designated GCS ≤13 at admission (P = 0.09; OR = 1.9), remote stroke (P = 0.009; OR = 2.9), and recurrence rate within 14 days (P = 0.001; OR = 3.3; with an incidence of 13%) as independent predictors for ASz/SE. Overall, patients with ASz/SE had significantly unfavorable outcome at discharge (54.7%; P < 0.001) and follow-up (39.5%; P < 0.001) with only slight improvement. Late seizures occurred in 3.8% within follow-up period. Any patient with SE had an unfavorable outcome at discharge without any improvement at follow-up having a mortality rate of 14.2%. CONCLUSION: Independent predictors for ASz/SE are GCS ≤13 at admission, remote stroke, and recurrent hematoma in patients with cSDH, which is associated with worse functional outcome, particularly those with SE. Due to the higher rate of seizures than recurrence rate, a routine pre- and postoperative EEG besides CT is recommended.

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review.

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation. METHODS: A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour volume" and "prognostic factors". RESULTS: After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results. CONCLUSION: The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Cisplatin-Based Chemotherapy for Testicular Germ Cell Tumors: Complication Rates of Peripheral versus Central Venous Administration.

OBJECTIVE: Despite the low local toxicity of the used agents, Cisplatin-based chemotherapy (CBP) for patients with testicular germ cell tumors (TGCT) is mostly delivered via a central venous access (CVA). Since 2008, CBP is given peripherally in our hospital. METHODS: Medical reports of TGCT patients who received CBP between September 1991 and August 2014 were evaluated. Complications regarding the way of administration (CVA vs. peripheral venous catheter [PVC]) were classified according to the Common Terminology Criteria of Adverse Events. The complication rates were compared using chi square test and propensity score matching. RESULTS: During 288 cycles in 109 patients, 85 complications (29.5%) were observed with similar rates for overall (PVC 31.3%, CVA 29.9%; p = 0.820) and grade I complications (21.3%, 25.4%; p = 0.470). More grade II complications were observed in the PVC group (10.0 vs. 1.5%; p < 0.001). Grade III complications requiring invasive treatment were found only in the CVA group (3.0%; p = 0.120). Using propensity score matching, no differences in overall (p = 0.950), grade I (p = 0.540) and grades II/III (p = 0.590) complications were seen. CONCLUSION: The peripheral and central administration of CBP has similar overall complication rates. Despite more grade II complications, the peripheral administration of CBP is a safe alternative for TGCT patients. Additionally, no severe grade III complications occurred.