Early surgery prolongs professional activity in IDH mutant low-grade glioma patients: a policy change analysis

BackgroundUntil 2015, Dutch guidelines recommended follow-up and biopsy rather than surgery as initial care for suspected low-grade gliomas (LGG). Given evidence that surgery could extend patient survival, our center stopped following this guideline on January 1, 2010 and opted for early maximal safe resection of LGG. The effects of early surgery on the ability of patients to work remains little documented. MethodsA total of 104 patients operated on at our center between January 2000 and April 2013 and diagnosed with the WHO 2016 grade 2 astrocytoma, IDH mutant or oligodendroglioma, IDH mutant and deleted 1p19q were included. The clinical characteristics, survival, and work history of patients operated on before or after January 2010 were obtained from the patients' records and compared. The minimal follow-up was 8 years. ResultsAs per policy change, the interval between radiological diagnosis and first surgery decreased significantly after 2010. Likewise, before 2010, 25.8% of tumors were initially biopsied, 51.6% were resected under anesthesia, and 22.5% under awake conditions versus 14.3%, 23.8%, and 61.9% after this date (p < 0.001). The severity of permanent postoperative neurological deficits decreased after 2010. In total, 82.5% of the patients returned to work postoperatively before 2010 versus 100% after 2010. The postoperative control of epilepsy increased significantly after 2010 (74.4% vs. 47.9%). The median time from diagnosis to a definitive incapacity to work increased by more than 2 years after 2010 (88.7 vs. 62.2 months). ConclusionA policy shift towards early aggressive surgical treatment of IDH mutant LGG is safe and prolongs the patients' ability to work

International practice variation in perioperative laboratory testing in glioblastoma patients-a retrospective cohort study

Purpose Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers-Brigham and Women's Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. Methods All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. Results After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p < 0.001) and 4.7-fold (p < 0.001) higher, respectively, in BWH compared to UMCU patients. The estimated median laboratory costs per patient were 82 euros in UMCU and 256 euros in BWH. Furthermore, the likelihood of an abnormal test result was lower in BWH (odds ratio [OR] 0.75, p < 0.001), except when the prior test result was abnormal as well (OR 2.09, p < 0.001). Conclusions Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates

INTRODUCTION: The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma. METHODS: We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-δ) and (epithelial-) mesenchymal transition (NF-κB, C/EBP-β and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data. RESULTS: Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-β and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas. CONCLUSION: In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns

Transcriptomic landscape of breast cancers through mRNA sequencing

Breast cancer is a heterogeneous disease with a poorly defined genetic landscape, which poses a major challenge in diagnosis and treatment. By massively parallel mRNA sequencing, we obtained 1.2 billion reads from 17 individual human tissues belonging to TNBC, Non-TNBC, and HER2-positive breast cancers and defined their comprehensive digital transcriptome for the first time. Surprisingly, we identified a high number of novel and unannotated transcripts, revealing the global breast cancer transcriptomic adaptations. Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. Our study also identified common transcriptional regulatory elements, such as highly abundant primary transcripts, including osteonectin, RACK1, calnexin, calreticulin, FTL, and B2M, and “genomic hotspots” enriched in primary transcripts between the three groups. Thus, our study opens previously unexplored niches that could enable a better understanding of the disease and the development of potential intervention strategies

Comparing Glioblastoma Surgery Decisions Between Teams Using Brain Maps of Tumor Locations, Biopsies, and Resections

PURPOSE: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glioblastoma surgery decisions throughout the brain. METHODS: Adults undergoing first-time glioblastoma surgery from 2012 to 2013 performed by two neuro-oncologic teams were included. Patients had had a diagnostic biopsy or resection. Preoperative tumors and postoperative residues were segmented on magnetic resonance imaging in three dimensions and registered to standard brain space. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to compare patient referral bias, indication variation, and treatment variation. To evaluate the quality of care, subgroups of differentially resected brain regions were analyzed for survival and functional outcome. RESULTS: One team included 101 patients, and the other included 174; 91 tumors were biopsied, and 181 were resected. Patient characteristics were largely comparable between teams. Distributions of tumor locations were dissimilar, suggesting referral bias. Distributions of biopsies were similar, suggesting absence of indication variation. Differentially resected regions were identified in the anterior limb of the right internal capsule and the right caudate nucleus, indicating treatment variation. Patients with (n = 12) and without (n = 6) surgical removal in these regions had similar overall survival and similar permanent neurologic deficits. CONCLUSION: Probability maps of tumor location, biopsy, and resection provide additional information that can inform surgical decision making across multidisciplinary teams for patients with glioblastoma

The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain. RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines

Recurrent chromosome breakpoints in tumour cells may point to cancer genes, but not many have been molecularly characterised. We have used multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) on breast tumour cell lines to identify regions of chromosome break created by inversions, duplications, insertions and translocations on chromosomes 1, 5, 8, 12 and 17. We delineate a total of 136 regions of break, some of them occurring with high frequency. We further describe two examples of dual-colour FISH characterisation of breakpoints, which target the 1p36 and 5p11–12 regions. Both breaks involve genes whose function is unknown to date. The mbanding-FISH strategy constitutes an efficient first step in the search for potential cancer genes