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Background There is no standard treatment for patients with recurrent high-grade gliomas who progress after bevacizumab treatment. We evaluated the outcomes of re-irradiation combined with bevacizumab for patients refractory to bevacizumab. Methods Between January 2015 and September 2019, patients with progression after bevacizumab treatment were treated with re-irradiation combined with bevacizumab (25 Gy in five fractions). Results Fourteen patients [glioblastoma, isocitrate dehydrogenase (IDH) wild type (N = 6), glioblastoma, IDH mutant (N = 4), anaplastic astrocytoma, IDH wild type (N = 1), anaplastic astrocytoma, IDH mutant (N = 1), glioblastoma, not otherwise specified (N = 1) and radiologically diagnosed brainstem glioma (N = 1)] were included in this study. The median survival and progression-free survival times after re-irradiation combined with bevacizumab were 6.1 and 3.8 months, respectively. The 6-month survival and progression-free survival rates were 54.5 and 15.7%, respectively. Patients with a Karnofsky performance status of ≥70 tended to have longer median survival time (9.3 vs. 5.4 months, respectively; P = 0.058) and had a significantly longer median progression-free survival time (4.2 vs. 3.7 months, respectively; P = 0.046) than those with a Karnofsky performance status of Conclusions Re-irradiation combined with bevacizumab for patients with recurrent high-grade gliomas who progress after bevacizumab treatment was feasible. Re-irradiation combined with bevacizumab is a potential treatment option, especially for patients with a Karnofsky performance status of ≥70.

Background Primary central nervous system lymphoma (PCNSL) responds relatively quickly to chemotherapy or radiotherapy. However, determination of a complete response after treatment is often difficult because of extremely light residual contrast enhancement on magnetic resonance images due to the effects of microhemorrhages and scar tissue formation. These small enhancing lesions define an unconfirmed complete response. The aim of this study was to investigate the usefulness of carbon-11-labeled methionine (11C-Met) positron-emission tomography (PET) for determining the treatment response of PCNSL. Methods Data for 36 patients who were treated for PCNSL between 2011 and 2015 and underwent magnetic resonance imaging and 11C-Met PET were reviewed. Magnetic resonance imaging findings were classified as complete response, unconfirmed complete response, and tumor mass (a composite of partial response, stable disease and progressive disease). PET images were evaluated, standardized uptake values were quantified, and the tumor-to-normal tissue count ratio (TNR) was calculated. Receiver operating characteristic curves were generated to determine the optimal cutoff TNRs. Results The optimal TNRs for differentiating complete response and unconfirmed complete response from tumor mass were 1.83 (area under the curve, 0.951) and 1.80 (area under the curve, 0.932), respectively. The corresponding sensitivity and specificity values for the diagnosis of tumor mass were 82.4 and 100%, respectively, in the complete response group and 85.3 and 85%, respectively, in the unconfirmed complete response group. Conclusions A TNR of ≥1.80 can aid in the detection of active PCNSL using 11C-Met PET. Thus, 11C-Met-PET may be a useful tool for accurate evaluation of the treatment efficacy in PCNSL.

OBJECTIVE Glioblastomas with isocitrate dehydrogenase 1/2 mutations comprise a biologically distinct subgroup of glioblastomas. We studied isocitrate dehydrogenase 1/2 mutant glioblastomas at the clinical, molecular and radiological levels to define their clinical features, including the prognostic value of isocitrate dehydrogenase 1/2 mutations compared with isocitrate dehydrogenase 1/2 wild-type glioblastomas. METHODS We investigated 128 newly diagnosed glioblastoma patients who were treated at our institute between January 2005 and May 2013. Isocitrate dehydrogenase 1/2 mutation status was determined using pyrosequencing. O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation and 1p/19q co-deletions were also analyzed using pyrosequencing and multiplex ligation-dependent probe amplification, respectively. RESULTS Isocitrate dehydrogenase 1/2 mutations were detected in 10 of 128 patients (7.8%). Isocitrate dehydrogenase 1/2 mutations were correlated with a younger age, the presence of an oligodendroglial component and 1p/19q co-deletions and a longer survival time. The interval from initial symptom to initial operation did not differ according to isocitrate dehydrogenase 1/2 mutation status (median interval: 2.3 versus 1.2 months; P = 0.13). Two of three isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions had an oligodendroglial component and were associated with a prolonged survival time. Multivariate analysis of 90 patients treated with temozolomide-based chemoradiotherapy indicated that age, extent of resection, postoperative Karnofsky performance score and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation were correlated with better survival. Isocitrate dehydrogenase 1/2 mutations showed a trend for improved survival (P = 0.068). CONCLUSIONS Most isocitrate dehydrogenase 1/2 mutant glioblastomas have a short clinical history, and some isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions behave like oligodendroglial tumors. Isocitrate dehydrogenase 1/2 mutations may have a positive prognostic impact on the Japanese population.

Objective: Although the number of long-term survivors of glioma has increased, there has been little research on the health-related quality of life of long-term survivors of Grade II glioma following treatment with surgery, radiotherapy and chemotherapy. In this study, we aimed to document the health-related quality of life of people diagnosed with Grade II glioma who had survived >10 years with no evidence of disease at the time of the health-related quality of life survey. Methods: To investigate the health-related quality of life of Grade II glioma survivors without evidence of disease, we surveyed 50 patients 0-20 years after their initial treatments. Each patient completed a multi-part health-related quality of life questionnaire. Based on these surveys, we examined the relationships between health-related quality of life scores and time since initial treatment, Karnofsky Performance Scale scores at the time of the survey, and history of recurrence, radiotherapy and chemotherapy. Results: Excepting bladder control, long-term survivors maintained their quality of life as determined by comparing patients surveyed < 5 and ≥ 10 years after their initial treatment (P < 0.05). Neither radiotherapy nor chemotherapy at the initial treatment was observed to affect health-related quality of life. However, a history of recurrence was significantly associated with deteriorations in many health-related quality of life functional and symptom scores. The Karnofsky Performance Scale scores of patients with a history of recurrence were significantly lower than those without it (P = 0.02). This deterioration was observed in both univariate and multivariate analyses. Conclusions: Our results indicate that declines in health-related quality of life among long-term survivors of Grade II glioma mainly result from impaired Karnofsky Performance Scale, which is a consequence of disease recurrence.

Background There is increasing evidence that MTX-based chemotherapy is superior to HD-MTX alone. Rituximab (RTX) is effective in a variety of B-cell lymphomas and may enter the brain. The purpose of this study is to evaluate the addition of RTX to HD-MTX in recurrent primary central nervous system lymphoma (PCNSL). Methods Patients diagnosed with recurrent PCNSL at our institution between 2004 and 2009 were treated with HD-MTX (3.5-5.5 g/m2) every 2 weeks. From 2010, RTX (375 mg/m2) was administered every 2 weeks along with HD-MTX. Results Fifteen recurrences in 10 patients were treated with HD-MTX alone (MTX group). Another 15 recurrences in 10 patients were treated with RTX and HD-MTX (RTX group). In 13 (86.6%) of the 15 recurrences in both groups the pre-planned chemotherapy cycles were completed. In the MTX group, 10/15 (66.6%) recurrences achieved a complete response (CR/CRu), 2/15 (13.3%) recurrences achieved a partial response (PR) and 3/15 (20%) recurrences had progressive disease (PD). In the RTX group, the CR/CRu, PR and PD rates were the same as that in the MTX group. The median time to tumor progression (mTTP) was 9.1 months (range, 1.4-120.9 months) in the MTX group and 7.8 months (range, 0.9-52.3 months) in the RTX group. We found no significant difference in mTTP (9.1 vs. 7.8 months, HR 1.02, 95% CI 0.48-2.18, P = 0.94) between the two groups. All treatment-related toxicities were manageable without any severe events. Conclusions The addition of RTX to HD-MTX may not be a promising strategy for recurrent PCNSL. A future study with a larger sample size, longer follow-up, or different RTX dosing/schedule is warranted.