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Background Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort. Methods Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria. Results A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O 6 - methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p <.001 and p =.029, respectively) and 6 months (p =.045 and p =.034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p =.838). Conclusions PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings. [ABSTRACT FROM AUTHOR]

Background New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Methods Retrospective analysis of adult patients operated for glioblastoma in the population of South–Eastern Norway. Patients were stratified into Pre-temozolomide- (2003–2005), temozolomide- (2006–2012), and resection-focused period (2013–2019) and evaluated according to age and EOR. Results The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; P  < .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (P  < .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; P  < .001). The median survival doubled in patients ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. Conclusions We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes. [ABSTRACT FROM AUTHOR]

Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3‐wildtype primary brain tumors only in adult‐type diffuse gliomas and are associated with a better outcome compared to their IDH‐wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH‐mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH‐sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH‐mutant, and BRAF p.V600E‐mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH‐mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options. [ABSTRACT FROM AUTHOR]

Objective: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. Design: Prospective controlled study. Methods: We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. Results: Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P<0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. Conclusion: High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma). [ABSTRACT FROM AUTHOR]