scholarly journals Precise enhancement quantification in post-operative MRI as an indicator of residual tumor impact is associated with survival in patients with glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alonso Garcia-Ruiz ◽  
Pablo Naval-Baudin ◽  
Marta Ligero ◽  
Albert Pons-Escoda ◽  
Jordi Bruna ◽  
...  
Keyword(s):  
Subjective Evaluation ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Primary Brain Tumor ◽  
Optimal Time ◽  
Post Surgery ◽  
Objective Evidence ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Remnant ◽  
Computational Image Analysis

AbstractGlioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p < 0.001). The prognostic value of several imaging and clinical variables was analyzed individually and combined (radiomics AUC 0.71, p = 0.07; combined AUC 0.72, p < 0.001). Residual enhancement thickness and radiomics complemented clinical data for prognosis stratification in patients with glioblastoma. Significant results were only obtained for scans performed between 24 and 72 h after surgery, raising the possibility of confounding non-tumor enhancement in very early post-surgery MRI. Regarding the extent of resection, and in agreement with recent studies, the association between the measured tumor remnant and survival supports maximal safe resection whenever possible.

Estimating Risk of Pituitary Apoplexy after Resection of Giant Pituitary Adenomas

2021 ◽  
Author(s):  
John T. Butterfield ◽  
Takako Araki ◽  
Daniel Guillaume ◽  
Ramachandra Tummala ◽  
Emiro Caicedo-Granados ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Apoplexy ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Morbidity And Mortality ◽  
Surgical Approaches ◽  
Subtotal Resection ◽  
Advantages And Disadvantages ◽  
Cranial Nerve Palsies ◽  
Giant Pituitary Adenomas

Abstract Background Pituitary apoplexy after resection of giant pituitary adenomas is a rare but often cited morbidity associated with devastating outcomes. It presents as hemorrhage and/or infarction of residual tumor in the postoperative period. Because of its rarity, its incidence and consequences remain ill defined. Objective The aim of this study is to estimate the rate of postoperative pituitary apoplexy after resection of giant pituitary adenomas and assess the morbidity and mortality associated with apoplexy. Methods A systematic review of literature was performed to examine extent of resection in giant pituitary adenomas based on surgical approach, rate of postoperative apoplexy, morbidities, and mortality. Advantages and disadvantages of each approach were compared. Results Seventeen studies were included in quantitative analysis describing 1,031 cases of resection of giant pituitary adenomas. The overall rate of subtotal resection (<90%) for all surgical approaches combined was 35.6% (95% confidence interval: 28.0–43.1). Postoperative pituitary apoplexy developed in 5.65% (n = 19) of subtotal resections, often within 24 hours and with a mortality of 42.1% (n = 8). Resulting morbidities included visual deficits, altered consciousness, cranial nerve palsies, and convulsions. Conclusion Postoperative pituitary apoplexy is uncommon but is associated with high rates of morbidity and mortality in subtotal resection cases. These findings highlight the importance in achieving a maximal resection in a time sensitive fashion to mitigate the severe consequences of postoperative apoplexy.

CBIO-19. GENOME SHREDDING ENABLES CRISPR-MEDIATED GLIOBLASTOMA ONCOLYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi31-vi31
Author(s):  
Christof Fellmann ◽  
I-Li Tan ◽  
Alexendar Perez ◽  
Rachel Lew ◽  
Karen Zhu ◽  
...  
Keyword(s):  
Residual Tumor ◽  
Therapy Resistance ◽  
Primary Brain Tumor ◽  
Therapeutic Modality ◽  
Dna Double Strand Breaks ◽  
Innovative Treatment ◽  
Treatment Regimens ◽  
Epigenetic Profile ◽  
Treatment Paradigm ◽  
Species Specific

Abstract Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults 1. Despite multimodal treatment regimens including surgical resection, radio- and chemotherapy, the growth of residual tumor often results in therapy resistance and ultimately death. GBMs are highly diffuse and exhibit extensive intratumoral heterogeneity 2,3, confounding diagnostic efforts and presenting opportunities for therapy evasion. Therefore, innovative treatment paradigms that can efficiently eliminate GBM cells irrespective of their mutational and epigenetic profile are urgently needed. CRISPR technologies have revolutionized medicine by enabling targeted genome editing through RNA-guided introduction of DNA double-strand breaks 4,5. Here, we show that CRISPR-Cas9 mediated genome fragmentation through targeting of highly repetitive loci, termed “genome shredding”, enables rapid and robust elimination of GBM cells. We characterized genome shredding across mammalian and vertebrate cells, and identified optimal repetitive pan-vertebrate and species-specific loci. Genome shredding is equally effective in temozolomide (TMZ)-sensitive and -resistant GBM cells, and multi-cycle treatment regimens are feasible. Importantly, when deployed in intracerebral GBM xenografts through local delivery, CRISPR-Cas9 genome shredding efficiently eliminated all targeted cells. Together, genome shredding enables the rapid and efficient fragmentation of a target cell’s genome and subsequent DNA damage-induced cell death. This provides an innovative treatment paradigm that is independent of a tumor’s mutational and epigenetic profile and leverages CRISPR-Cas9 as a breakthrough therapeutic modality for GBM.

scholarly journals Shape matters: morphological metrics of glioblastoma imaging abnormalities as biomarkers of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Haylye White ◽  
Kamila M. Bond ◽  
Maciej M. Mrugala ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Tumor Location ◽  
Primary Brain Tumor ◽  
Resonance Imaging ◽  
Significant Relationships ◽  
Biological Phenomena ◽  
Microenvironmental Factors ◽  
Magnetic Resonance Imaging Mri ◽  
The Relationship ◽  
Standard Magnetic Resonance Imaging

AbstractLacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, a morphological measure of the complexity of pixel arrangement, have shown relationships with outcome across a variety of cancers. However, the application of these metrics to glioblastoma (GBM), a very aggressive primary brain tumor, has not been fully explored. In this project, we computed lacunarity and fractal dimension values for GBM-induced abnormalities on clinically standard magnetic resonance imaging (MRI). In our patient cohort (n = 402), we connect these morphological metrics calculated on pretreatment MRI with the survival of patients with GBM. We calculated lacunarity and fractal dimension on necrotic regions (n = 390), all abnormalities present on T1Gd MRI (n = 402), and abnormalities present on T2/FLAIR MRI (n = 257). We also explored the relationship between these metrics and age at diagnosis, as well as abnormality volume. We found statistically significant relationships to outcome for all three imaging regions that we tested, with the shape of T2/FLAIR abnormalities that are typically associated with edema showing the strongest relationship with overall survival. This link between morphological and survival metrics could be driven by underlying biological phenomena, tumor location or microenvironmental factors that should be further explored.

Comparison of Outcomes following Primary and Repeat Resection of Craniopharyngioma

2021 ◽  
Author(s):  
Alexander A. Aabedi ◽  
Jacob S. Young ◽  
Ryan R. L. Phelps ◽  
Ethan A. Winkler ◽  
Michael W. McDermott ◽  
...  
Keyword(s):  
Surgical Approach ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Primary Resection ◽  
Endocrine Function ◽  
Surgical Approaches ◽  
Subtotal Resection ◽  
Limited Data ◽  
Time To Recurrence ◽  
Skull Base Lesions

Abstract Introduction The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.

scholarly journals MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy

2019 ◽  
Vol 28 (16) ◽  
pp. 2738-2751 ◽  
Author(s):  
Ana M S Cardoso ◽  
Madalena Sousa ◽  
Catarina M Morais ◽  
Liliana R Oancea-Castillo ◽  
Anne Régnier-Vigouroux ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cell Metabolism ◽  
Combined Therapy ◽  
Treatment Options ◽  
Primary Brain Tumor ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Current Standard ◽  
Aberrant Expression ◽  
Post Surgery

Abstract Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.

scholarly journals NIMG-06. OUR THERAPEUTIC STRATEGIES FOR GLIOBLASTOMA: INTRAOPERATIVE SUPPORT SYSTEMS [INTRAOPERATIVE MRI, PET, 5-AMINOLEVULINIC ACID (5-ALA)] AND NEOADJUVANT CHEMOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi162-vi162
Author(s):  
Keisuke Miyake ◽  
Daisuke Ogawa ◽  
Masaki Okada ◽  
Tetsuhiro Hatakeyama ◽  
Takashi Tamiya
Keyword(s):  
Pet Imaging ◽  
Aminolevulinic Acid ◽  
Performance Status ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extraction Rate ◽  
Intraoperative Mri ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Extraction

Abstract OBJECTIVE Neuronavigation systems with magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) are routinely used in glioblastoma surgery. Residual tumor identified using intraoperative MRI (IoMRI) or 5-aminolevulinic acid (5-ALA) fluorescence is removed. Neoadjuvant bevacizumab therapy is offered to patients with low Karnovsky performance status (KPS) or with tumors in eloquent regions. We evaluated the usefulness of neoadjuvant bevacizumab therapy. METHODS Twelve patients with glioblastoma with low KPS or tumors in eloquent regions on multiple PET and IoMRI evaluations were enrolled between January 2016 and April 2019. Six had received neoadjuvant bevacizumab before surgery; six had not. Postsurgical 5-ALA fluorescence (strong, vague, and none) tumor extraction rate, residual volume on MRI and PET imaging, and prognosis in the patients with and without bevacizumab were compared. RESULTS In patients with bevacizumab adjuvant therapy, the KPS scores immediately prior to surgery were 90 in 3 cases, 80 in 2, and 70 in 1. The scores in patients without bevacizumab were 50 in 2 and 40 in 4. The 5-ALA fluorescence in patients with bevacizumab was vague in one and none in five. Vague fluorescence was noted in all six patients without bevacizumab. Tumor extraction rates in patients with vs. those without bevacizumab were 97.6% vs. 91.5% by T1-Gd, 95.4% vs. 99.9% by MET, 96.2% vs. 90.2% by FLT, and 97% vs. 92% by FMISO. Corresponding residual volumes (ml) were (0.6 vs. 1.7) for T1-Gd, 1.2 vs. 2.9 for MET, 1.0 vs. 2.1 for FLT, and 0.5 vs. 1.1 for. FLT. Median progression free survival (PFS) was 10.1 vs. 4.9 months; median overall survival (OS) was 15.7 vs. 13.3 months. CONCLUSIONS Neoadjuvant bevacizumab therapy improved KPS at the time of surgery, increased extraction rate, reduced residual tumor volume, and improved PFS and OS prognosis.

scholarly journals Indocyanin Green Videoangiography Study of Hemangioblastomas

2011 ◽  
Vol 38 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Yasuo Murai ◽  
Koji Adachi ◽  
Fumihiro Matano ◽  
Kojiro Tateyama ◽  
Akira Teramoto
Keyword(s):  
Residual Tumor ◽  
Preoperative Embolization ◽  
Surgical Removal ◽  
Vascular Differentiation ◽  
Brain Surface ◽  
Contrast Enhanced ◽  
Preoperative Magnetic Resonance ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Angiographic Findings

Abstract:Objective:We present herein the intraoperative indocyanin green videoangiography (ICGVAG) findings for three cases of cerebellar hemangioblastoma (HB).Cases:Cerebellar HB was detected in three patients presenting with symptoms of vertigo and/or headaches and diagnosed on the basis of preoperative magnetic resonance imaging (MRI) and cerebral angiographic findings. Preoperative embolization of the tumor feeding artery was not performed in any of the patients. None of the patients underwent any procedure prior to ICGVAG that would affect the ICG findings, such as perilesional hemostatic coagulation or ablation. In each patient, it was possible to judge the approximate location of the tumor in relation to the brain surface and to distinguish the feeding and draining vessels. Following resection of the tumor, ICGVAG images confirmed that the mural nodule had been eliminated. None of the patients required blood transfusion, either during or after the surgery. For each patient, the lesion was pathologically confirmed as HB, postoperative contrast-enhanced MRI confirmed the absence of residual tumor, and diffusion-weighted MRI revealed no ischemic changes.Results:Differentiation of feeding and draining vessels in the region of the lesion is particularly important for successful surgical removal of HB. In the present three patients, ICGVAG findings enabled easy vascular differentiation and were also useful for confirming that there was no residual tumor. Indocyanin green videoangiography was concluded to be useful for safe resection of HB.

scholarly journals Direct Evidence of Plasticity within Human Primary Motor and Somatosensory Cortices of Patients with Glioblastoma

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
William R. Gibb ◽  
Nathan W. Kong ◽  
Matthew C. Tate
Keyword(s):  
Glioblastoma Multiforme ◽  
Direct Evidence ◽  
Standard Of Care ◽  
Extent Of Resection ◽  
Brain Regions ◽  
Primary Brain Tumor ◽  
Indirect Measures ◽  
Somatosensory Cortices ◽  
New Finding ◽  
Subcortical Regions

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders.

Ependymomas

2018 ◽  
Author(s):  
Paul Klimo ◽  
Nir Shimony
Keyword(s):  
Molecular Subtypes ◽  
Extent Of Resection ◽  
Postoperative Radiation ◽  
Resonance Imaging ◽  
Posterior Fossa Tumors ◽  
Total Resection ◽  
Cerebrospinal Fluid Diversion ◽  
Neural Axis ◽  
Magnetic Resonance Imaging Mri ◽  
Severe Hydrocephalus

Pediatric posterior fossa tumors are usually ependymoma, pilocytic astrocytoma, or medulloblastoma. Ependymoma appears well-demarcated with heterogeneous enhancement on magnetic resonance imaging (MRI). Full neural axis MRI is indicated to assess for metastatic disease. Management is typically surgical resection of the tumor, with consideration for cerebrospinal fluid diversion if patients present with severe hydrocephalus. Extent of resection of the tumor is the most important factor in predicting recurrence and overall survival, and gross total resection is ideal. Infratentorial ependymomas have 2 molecular subtypes, which has implications for responsiveness to adjuvant therapy and prognosis. Infratentorial ependymomas are biologically different from supratentorial ependymomas. Postoperative radiation improves local control.

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