Utility of gene tumor expression of VEGF, FOXM1*3 and CD-133 on diagnosis and prognosis of brain gliomas

Objective. This paper seeks to quantify the normalized expression of transcripts FOXM1*3, VEGF, CD133, and MGMT and their relation with the histopathological and molecular diagnosis and with the probability of estimating tumor progression-free survival of gliomas. Methods. A cohort of patients was made up of patients aged over 18 years with a histological and molecular diagnosis of gliomas from the year 2011 to 2018. The patients had a complete tumor resection. Patients with high-grade glioma received adjuvant management (temozolamide and radiotherapy). Clinical and imaging follow-up was carried out periodically to identify the time of progression free survival (PFS). Results. Ninety-one patients (age range, 18-85 years) comprised the study cohort with a predominance of males. The expression of FOXM1*3, VEGF, and CD133 allowed the differentiation of astrocytomas grade II from GBM. ROC curves proved statistically significant in the GBM model (p <0.05), demonstrating greatest sensitivity with FOXM1*3 (91%), and greatest specificity with VEGF (93%). The age-adjusted Cox multivariate model established that a PFS50% of 25 months corresponds to a median value of 5.3 for VEGF and 0.42 for CD133. Conclusions The normalized expression of transcripts FOXM1*3, VEGF, and CD133 allow us to estimate the probability of PFS, especially in gliomas grades II and IV; likewise, their overexpression defines the diagnosis of GBM.

Download Full-text

FLGS-05. Maximal safe glioma resection using high resolution exoscope with 5-ALA-induced fluorescence

Neuro-Oncology ◽

10.1093/neuonc/noab196.909 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi226-vi227

Author(s):

Kuniaki Saito ◽

Nobuyoshi Sasaki ◽

Keiichi Kobayashi ◽

Hirofumi Nakatomi ◽

Yoshiaki Shiokawa ◽

...

Keyword(s):

High Resolution ◽

Blue Light ◽

Tumor Resection ◽

Progression Free Survival ◽

High Grade Glioma ◽

Lower Grade ◽

High Grade ◽

Surgical Morbidity ◽

Total Resection ◽

Free Survival

Abstract INTRODUCTION 5-aminolevulinic acid (5-ALA) guided surgery has been reported to prolong progression-free survival of patients with high grade glioma. Although blue-light capable microscope enables us to detect fluorescence intraoperatively, visualization of anatomy is difficult under blue-light microscope. On the other hand, exoscope permits to visualize both fluorescence and anatomy under blue-light conditions. We introduce our glioma surgery using an exoscope equipped with a 5-ALA fluorescence visual system. METHODS We attempted maximal safe resection for the patients with high grade glioma using 3D/4K exoscope with 5-ALA-induced fluorescence, neuronavigation, and electrophysiological monitoring or awake mapping. Visualization of fluorescence and anatomy under blue light, extent of resection, morbidity, and postoperative infarction were retrospectively reviewed. RESULTS Twenty patients (age 26–79, male 10/female 10, glioblastoma 11/lower grade glioma 9) underwent exoscopic tumor removal. Intraoperative fluorescence was observed in 100% of the tumor with gadolinium enhancement. Surrounding structures such as white matter, vessels and nerves were clearly visualized under blue light. Even perforators were visible and could be preserved. Supra-total resection and gross total resection of gadolinium-enhancing tumor was achieved in 6 (30%) and 10 (50%) patients, respectively. Surgical morbidity included hemianopsia in 1 patient and transient hemiparesis in 1 patient. Postoperative infarction was observed in 2 (10%) patients, which tended to be lower compared to 23 of 77 (29.9%) patients with glioblastoma who underwent tumor resection with fluorescence-equipped microscope(p=0.05). CONCLUSION Clear visualization of 5-ALA-indced tumor fluorescence and anatomical structures with use of high resolution exoscope help maximal safe tumor resection. Longer progression-free survival is expected as a result of greater extent of tumor resection.

Download Full-text

IMG-14. DEVELOPING A PREDICTIVE GRADING MODEL FOR CHILDREN WITH GLIOMAS BASED ON DIFFUSION KURTOSIS IMAGING METRICS: ACCURACY AND CLINICAL CORRELATIONS WITH SURVIVAL

Neuro-Oncology ◽

10.1093/neuonc/noaa222.349 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii357-iii358

Author(s):

Ioan Paul Voicu ◽

Antonio Napolitano ◽

Alessia Carboni ◽

Lorenzo Lattavo ◽

Andrea Carai ◽

...

Keyword(s):

Progression Free Survival ◽

High Grade Glioma ◽

Diffusion Kurtosis Imaging ◽

Low Grade ◽

Free Survival ◽

Kaplan Meier ◽

Model Predictions ◽

Probability Prediction ◽

Grading Model ◽

Diffusion Kurtosis

Abstract PURPOSE To develop a predictive grading model based on diffusion kurtosis imaging (DKI) metrics in children affected by gliomas, and to investigate the clinical impact of the model via correlations with overall survival and progression-free survival. MATERIALS AND METHODS We retrospectively studied 59 children (33M, 26F, median age 7.2 years) affected by gliomas on a 3T magnet. Patients with tumor locations other than infratentorial midline were included. Conventional and DKI sequences were obtained. Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were obtained. Whole tumor volumes (VOIs) were segmented semiautomatically. Mean DKI values were calculated for each metric. The quantitative values from DKI-derived metrics were used to develop a predictive grading model with penalized logistic regression (glmnet package, R). Elasticnet regularization was used to avoid model overfitting. Fitted model coefficients from each metric were used to develop a probability prediction of a high-grade glioma (HGG). Grading accuracy of the resulting probabilities was tested with ROC analysis. Finally, model predictions were correlated to progression-free survival (PFS) with a Kaplan-Meier analysis. RESULTS The cohort included 46 patients with low-grade gliomas (LGG) and 13 patients with HGG. The developed model predictions yielded an AUC of 0.946 (95%CI: 0.890–1). Model predictions were significantly correlated with PFS (23.1 months for HGG vs 34.7 months for LGG, p<0.004). CONCLUSION In our cohort, a DKI-based predictive model was highly accurate for pediatric glioma grading. DKI-based model predictions were significantly correlated with progression-free survival.

Download Full-text

Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2012005000017 ◽

2013 ◽

Vol 71 (1) ◽

pp. 31-34 ◽

Cited By ~ 7

Author(s):

André de Macedo Bianco ◽

Flavio Key Miura ◽

Carlos Clara ◽

Jose Reynaldo W. Almeida ◽

Clemar Correa da Silva ◽

...

Keyword(s):

Overall Survival ◽

Tumor Resection ◽

Progression Free Survival ◽

Subtotal Resection ◽

Low Grade ◽

Brain Areas ◽

Free Survival ◽

Eloquent Areas ◽

Eloquent Area ◽

Extent Of Surgical Resection

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

Download Full-text

KAI-1 Expression in Pediatric High-Grade Osteosarcoma

Pediatric and Developmental Pathology ◽

10.2350/11-05-0137.1 ◽

2006 ◽

Vol 9 (3) ◽

pp. 219-224 ◽

Cited By ~ 2

Author(s):

Patrick J. Leavey ◽

Charles Timmons ◽

William Frawley ◽

Donald Lombardi ◽

Raheela Ashfaq

Keyword(s):

Prognostic Markers ◽

Clinical Phenotype ◽

Tumor Resection ◽

Progression Free Survival ◽

Surface Proteins ◽

High Grade ◽

Free Survival ◽

Treatment Groups ◽

High Grade Osteosarcoma

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.

Download Full-text

Could Primary Tumor Resection Improve Survival in Metastatic Breast Cancer?

International Journal of Scientific Research and Management ◽

10.18535/ijsrm/v9i07.mp04 ◽

2021 ◽

Vol 9 (07) ◽

pp. 422-428

Author(s):

Rafaela Aparecida Dias de Oliveira ◽

Lyvia Aparecida Dias de Oliveira ◽

Marília Davoli Abella Goulart ◽

Maria Clara Faustino Linhares

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Systemic Therapy ◽

Primary Tumor ◽

Tumor Resection ◽

Metastatic Breast ◽

Progression Free Survival ◽

Primary Tumor Resection ◽

Free Survival

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size. Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.

Download Full-text

OS14 - 208 The prognostic role of pre-operative complete blood count (CBC) in progression-free survival in patients with meningioma

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.344 ◽

2016 ◽

Vol 43 (S4) ◽

pp. S6-S6

Author(s):

S. Karimi ◽

P.D. Tonge ◽

L. Gonen ◽

R. Tabasinejad ◽

G. Zadeh ◽

...

Keyword(s):

Complete Blood Count ◽

Tumor Resection ◽

Progression Free Survival ◽

Final Analysis ◽

Tumor Grade ◽

Prognostic Information ◽

Free Survival ◽

Univariate Analyses

Factors which might influence outcome in patients with meningioma are not well-understood. Previous studies have examined associations of laboratory blood values including hemoglobin levels with patient outcomes in cancer. We hypothesized those changes in CBC before tumor resection can be used as one of the prognostic factors for tumor recurrence/progression in meningioma. To address this, we gathered the clinical and pre-operative CBC results for final analysis from 226 patients (64 males and 162 females) who underwent craniotomy for primary meningioma (grades: 157 WHO GI, 59 GII, 10 GIII) at our institution between 2001 and 2015.Individual parameters were analyzed for correlation with progression-free survival. The median recurrence free survival (RFS) was not reached and follow-up ranged 0.3-14 years. Fifty-six patients (25%) had anemia and 30% of the patients showed leukocytosis using standard cut-offs. On univariate analyses, low hemoglobin (Hb) level, as well as high leukocytes (Lkc), neutrophil (Neutro) and monocyte counts correlated with worse RFS. As expected, tumor grade was correlated with RFS. Low Hb level, high Lkc and Neutro counts were all significantly associated with RFS after adjusting for grade. Strikingly, 32% of patients with pre-operative anemia experienced a recurrence at 5 years, compared with only 11% of non-anemic patients. Conclusion: In this exploratory study, we find that pre-operative CBC data, which is readily available, may contain prognostic information relevant to subsequent risk of recurrence or progression in meningioma. While the biological mechanism for these associations is not clear, they represent hypotheses for further investigation.

Download Full-text

Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery

Operative Neurosurgery ◽

10.1093/ons/opz082 ◽

2019 ◽

Vol 18 (1) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

Christoph Bettag ◽

Abdelhalim Hussein ◽

Daniel Behme ◽

Theoni Maragkou ◽

Veit Rohde ◽

...

Keyword(s):

Tumor Tissue ◽

Aminolevulinic Acid ◽

Histopathological Examination ◽

Tumor Resection ◽

Progression Free Survival ◽

Extent Of Resection ◽

Complete Resection ◽

Free Survival ◽

Resected Tissue ◽

Microsurgical Resection

Abstract BACKGROUND Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope. OBJECTIVE To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection. METHODS 5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery. RESULTS Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor. CONCLUSION Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.

Download Full-text

Brainstem Low-Grade Gliomas in Children—Excellent Outcomes With Multimodality Therapy

Journal of Child Neurology ◽

10.1177/0883073816675547 ◽

2016 ◽

Vol 32 (2) ◽

pp. 194-203 ◽

Cited By ~ 11

Author(s):

Santhosh A. Upadhyaya ◽

Carl Koschmann ◽

Karin Muraszko ◽

Sriram Venneti ◽

Hugh J. Garton ◽

...

Keyword(s):

Progressive Disease ◽

Survival Rates ◽

Tumor Resection ◽

Progression Free Survival ◽

Low Grade ◽

University Of Michigan ◽

Single Institution ◽

Free Survival ◽

Low Grade Gliomas ◽

The University

Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy. Eight patients in the study had progressive disease; 5 initially resected tumors received chemotherapy at tumor relapse, all with partial or complete radiographic responses. Ten-year progression-free survival is 71% and overall survival, 100%. This single-institution retrospective study demonstrates excellent survival rates for children with brainstem low-grade gliomas. The efficacy of the well-tolerated chemotherapy in this series supports its role in the treatment of unresectable or progressive brainstem low-grade gliomas.

Download Full-text

Intramedullary spinal cord tumor resection

Neurosurgical FOCUS ◽

10.3171/2012.v2.focus12154 ◽

2012 ◽

Vol 33 (Suppl1) ◽

pp. 1

Author(s):

Mari L. Groves ◽

Patricia L. Zadnik ◽

Pablo F. Recinos ◽

Violette Renard ◽

George I. Jallo

Keyword(s):

Spinal Cord ◽

Spinal Cord Tumor ◽

Tumor Resection ◽

Progression Free Survival ◽

Low Grade ◽

High Definition ◽

En Bloc ◽

Intramedullary Spinal Cord ◽

Free Survival ◽

Intramedullary Spinal Cord Tumor

The authors present a case of a 27-year-old patient who presented with spastic gait and worsening difficulty walking over a 6 month period. Spinal MR imaging revealed a heterogeneously enhancing intramedullary spinal cord tumor (IMSCT) with associated syrinx in the cervical spine. The lesion was resected through posterior en bloc laminotomy, durotomy, and microscopic resection of the intramedullary component followed by laminoplasty reconstruction. Surgical resections with a goal of gross total resection can significantly improve overall survival and progression free survival in patients with low-grade IMSCT. The procedure is presented in an edited, high-definition format with accompanying narrative. The video can be found here: http://youtu.be/Ui9bn82PtP8.

Download Full-text