Galectin-1 (Gal-1) expression as a prognostic factor in patients with newly diagnosed glioblastoma (GB) treated with Stupp regimen (GLIOCAT study).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13526-e13526
Author(s):  
Noelia Vilarino ◽  
Neus Martinez-Bosch ◽  
Carmen Balana ◽  
Francesc Alameda ◽  
Anna Estival ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Initial Surgery ◽  
Newly Diagnosed Glioblastoma

e13526 Background: Gal-1 is a β-galactoside binding protein that plays an important role in cancer, promoting cell invasion, proliferation, migration, angiogenesis and evasion of the immune response. Gal-1 is involved in glioma progression and is related to tumor grade and poor clinical outcome. Gal-1 has been implicated in resistance to chemotherapy and as a potential mediator of resistance to anti-VEGF therapy. The aim of our study was to evaluate the prognostic significance of Gal-1 in a homogenous cohort of GB patients and to analyze its potential predictive value of response to bevacizumab at recurrence. Methods: A substudy of GLIOCAT, a multicenter study of newly diagnosed GB patients treated with standard Stupp regimen (previously reported). GLIOCAT enrolled 432 patients between 2005-2014. Tissue was available from 243 cases, from which a tissue microarray (TMA) was constructed. Gal-1 expression in tissue from initial surgery was analyzed by immunohistochemistry. Results were evaluated by three reviewers and quantified by H-score. Expression levels were correlated with clinical outcome, known GB prognostic factors and response to bevacizumab. Results: We defined a cut off for Gal-1 H-Score of >60 (cytoplasm) and >25 (nucleus). HighcytoplasmicGal-1 expression significantly correlated with worse OS and with a trend for shorter PFS. In the multivariate analysis KPS, age, MGMT methylation status and, extent of resection but not Gal-1 expression were independent prognostic factors for survival. Of 92 patients who received bevacizumab at recurrence, only 54 were included in the TMA, and only 1 had low Gal-1 expression. We couldn’t find any relationship with OS or PFS in this population. Conclusions: Gal-1 expression may represent a prognostic factor for GB patients treated with standard therapy. [Table: see text]

scholarly journals Postoperative Prolonged Mechanical Ventilation in Patients With Newly Diagnosed Glioblastoma—An Unrecognized Prognostic Factor

2020 ◽  
Vol 10 ◽  
Author(s):  
Patrick Schuss ◽  
Felix Lehmann ◽  
Niklas Schäfer ◽  
Christian Bode ◽  
Elisa Scharnböck ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Functional Outcome ◽  
Prolonged Mechanical Ventilation ◽  
Methylation Status ◽  
Significant Prognostic Factor ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

ObjectiveAlthough the treatment of glioblastoma patients is well established in neuro-oncological surgery, precious scarce data is available on patients with glioblastoma requiring postoperative prolonged mechanical ventilation (PMV). Therefore, the aim of the present study was to determine the influence of PMV on overall survival (OS) in patients with glioblastoma.MethodsPatients with newly diagnosed glioblastoma who had undergone surgical therapy and complete subsequent neuro-oncological treatment at the authors’ neuro-oncological center from January 2013 to December 2018 were selected and included in the further analysis. PMV was defined as mechanical ventilation for more than 24 h after surgery. Survival analyses were performed, including established prognostic factors such as age, Karnofsky performance score, MGMT-promoter methylation status and extent of resection.ResultsA total of 240 patients with newly diagnosed glioblastoma and subsequent surgical treatment were identified. 13 patients (5%) suffered from PMV during the treatment course of glioblastoma. All but one patient were successfully weaned from mechanical ventilation. Patients suffering from PMV achieved significantly less often favorable functional outcome after 3, 6, 9, and 12 months compared to patients without PMV. Multivariate analysis revealed PMV to constitute a significant prognostic factor for OS, independent of other prognostic factors (p<0.0001, OR 6.7, 95% CI 3.2–13.8).ConclusionsThe present study identifies PMV as significantly associated with impaired functional outcome and poor OS in patients suffering from newly diagnosed glioblastoma. These findings encourage further efforts to investigate/assess this prognostic factor in future studies.

scholarly journals Dose-Dense Temozolomide for Newly Diagnosed Glioblastoma: A Randomized Phase III Clinical Trial

2013 ◽  
Vol 31 (32) ◽  
pp. 4085-4091 ◽  
Author(s):  
Mark R. Gilbert ◽  
Meihua Wang ◽  
Kenneth D. Aldape ◽  
Roger Stupp ◽  
Monika E. Hegi ◽  
...  
Keyword(s):  
Methylation Status ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
Significant Difference ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Dense ◽  
The Impact

Purpose Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. Patients and Methods This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. Results A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue. Conclusion This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.

scholarly journals NIMG-37. DELAYED PSEUDOPROGRESSION IN TWO PATIENTS UNDERGOING TTFIELDS TREATMENT FOR NEWLY DIAGNOSED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii155-ii156
Author(s):  
Allison Lowman ◽  
Sarah Hurrell ◽  
Samuel Bobholz ◽  
Jennifer Connelly ◽  
Elizabeth Cochran ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Radiographic Progression ◽  
Methylation Status ◽  
Underlying Mechanism ◽  
Recurrent Glioblastoma ◽  
Newly Diagnosed ◽  
Methylguanine Dna Methyltransferase ◽  
Specific Effects ◽  
Newly Diagnosed Glioblastoma ◽  
Associated Risk Factors

Abstract PURPOSE Tumor treatment fields (TTFields) are approved by the FDA for newly diagnosed as well as recurrent glioblastoma (GBM). TTFields have been shown to extend survival by 4.9 months in newly diagnosed GBM, and a landmark overall survival rate of 13% at 5 years. However, the specific effects remain widely unknown, which has prevented widespread clinical use of this treatment. METHODS This case study examines two glioblastoma patients, IDH-1 wildtype, MGMT unmethylated, that received TTFields (Optune) in addition to maintenance temozolomide (TMZ) following radiation (RT). Both cases were followed using standard MR imaging. Second resections were performed due to radiographic progression of contrast enhancement. RESULTS Although imaging was concerning for tumor progression, pathology showed only treatment effect, ultimately leading to the diagnosis of pseudoprogression. Both patients fell outside the normal expected timeline for chemo-radiation induced pseudoprogression. Based on the pathology, both patients resumed treatment with TMZ/TTFields. One patient expired at 25 months and one is still alive. CONCLUSIONS Pathologic confirmation was essential for guiding further treatment and allowed patients to continue treatment that was effective despite contrary indications on imaging. These findings suggest that pathological confirmation should be strongly considered in patients receiving TMZ/TTFields who develop radiographic progression, potentially with a less invasive biopsy procedure. Future studies should look to characterize the underlying mechanism of interaction between TTFields/TMZ and quantify the prevalence, associated risk factors and whether there is a genotype more susceptible. Both patients reported here had O(6)-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM, and while about 60% of glioblastomas are diagnosed likewise, it is possible that MGMT methylation status plays a role in TTFields response. Better characterization of this phenomenon will improve treatment guidance, potentially reducing unnecessary surgeries and the discontinuance of successful therapies.

scholarly journals Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1422-1430 ◽  
Author(s):  
Dorothee Gramatzki ◽  
Philipp Kickingereder ◽  
Bettina Hentschel ◽  
Jörg Felsberg ◽  
Ulrich Herrlinger ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Proportional Hazards Model ◽  
Methylation Status ◽  
Residual Tumor ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Clinical Patient ◽  
Newly Diagnosed Glioblastoma

Objective:To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles.Methods:The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome.Results:Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7–20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7–23.3, vs 17.2 months, 95% CI 10.2–24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9–36.4, vs 33.2 months, 95% CI 25.3–41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4–1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8–3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status.Conclusion:These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles.Classification of evidence:This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.

RADT-13. SPARE TRIAL: SCALP-SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATING FIELDS FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi43-vi44
Author(s):  
Ryan Miller ◽  
Andrew Song ◽  
Ayesha S Ali ◽  
Voichita Bar-Ad ◽  
Nina, L Martinez ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Methylation Status ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Prospective Trials ◽  
Dose Constraints ◽  
Topical Medications

Abstract INTRODUCTION Current adjuvant treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. METHODS Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. RESULTS Thirty patients were enrolled. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median follow-up was 10.8 months (range 1.6 to 21.3 months). Twenty (66.7%) patients had unmethylated MGMT promotor and ten (33.3%) patients had methylated promoter. Scalp dose constraints were achieved for all patients. Skin adverse events (erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). The median PFS for the entire cohort was 9.1 months (at least 8.5 months, 95% confidence). The median PFS for patients with MGMT promoter methylation status was 11.4 months (at least 9.5 months, 95% confidence). Overall survival was not reached. CONCLUSIONS Concurrent TTFields with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

PATH-16. EVALUATION OF SEX-BASED DIFFERENCES IN CLINICAL OUTCOMES AND TUMOR GENOMICS IN PATIENTS WITH NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA RECEIVING CHEMORADIATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi118
Author(s):  
Diana Shi ◽  
Mary Jane Lim-Fat ◽  
Amin Nassar ◽  
Jared Woods ◽  
Gilbert Youssef ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Methylation Status ◽  
Multivariable Analysis ◽  
Extent Of Resection ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Loss Of Function ◽  
Female Sex

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.

scholarly journals PC3 - 152 Impact of Extent of Resection Upon Outcome in Newly Diagnosed Glioblastoma: A Study in the Molecular Era

2016 ◽  
Vol 43 (S4) ◽  
pp. S17-S18
Author(s):  
W.M.H. Sayeed ◽  
E. Batuyong ◽  
J.C. Easaw ◽  
M. Pitz ◽  
J.J.P. Kelly
Keyword(s):  
Multivariable Analysis ◽  
Extent Of Resection ◽  
Postal Code ◽  
Newly Diagnosed ◽  
Presenting Symptoms ◽  
Tumour Location ◽  
Newly Diagnosed Glioblastoma ◽  
Molecular Marker Analysis

For decades, debate has persisted regarding the role of surgical resection in newly diagnosed glioblastoma. There is increasing evidence that extent of resection (EoR) is an independent prognostic factor. Previous work has proposed the inclusion of EoR in a risk stratification algorithm but does not incorporate account recent advances in the molecular characterization of tumours. We set out to investigate the effect of EoR on overall survival (OS), and to develop a stratification algorithm incorporating both EoR and modern molecular markers for prognostication. HYPOTHESIS: Greater EoR is independently associated with improved OS. METHODS: We examined 190 consecutive cases of histopathologically confirmed newly-diagnosed glioblastoma who were operated upon between January 1, 2012 and December 31, 2014. Variables including age, sex, postal code, KPS, tumour location, presenting symptoms, treatment history, date of progression, date of reoperation, as well as MGMT, IDH, 1p/19q codeletion, and ATRX status were recorded. Preoperative and postoperative MRIs were reviewed and volumetric tumour burden will be analyzed and EoR will be calculated. RESULTS: Preliminary EoR calculations (n=18) show a positive correlation between EoR and OS. CONCLUSION: A correlation exists between EoR and OS, although multivariable analysis is planned to exclude potential confounders. MRI review, chart review including molecular marker analysis and EoR calculations are ongoing.

scholarly journals Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 939
Author(s):  
Young Ju Jeong ◽  
Hoon Kyu Oh ◽  
Hye Ryeon Choi ◽  
Sung Hwan Park
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Receptor Expression ◽  
Gene Methylation ◽  
Clinicopathologic Characteristics ◽  
Large Tumor ◽  
The Mean

Cluster of differentiation (CD) 73, which is encoded by the NT5E gene, regulates production of immunosuppressive adenosine and is an emerging checkpoint in cancer immunotherapy. Despite the significance of CD73 in immuno-oncology, the roles of the NT5E gene methylation in breast cancer have not been well-defined yet. Therefore, we aimed to investigate the prognostic significance of the NT5E gene methylation in breast cancer. The DNA methylation status of the NT5E gene was analyzed using pyrosequencing in breast cancer tissues. In addition, the levels of inflammatory markers and lymphocyte infiltration were evaluated. The mean methylation level of the NT5E gene was significantly higher in breast cancer than in normal breast tissues. In the analysis of relevance with clinicopathologic characteristics, the mean methylation levels of the NT5E gene were significantly higher in patients with large tumor size, high histologic grade, negative estrogen receptor expression, negative Bcl-2 expression, and premenopausal women. There was no difference in disease-free survival according to the methylation status of the NT5E gene. We found that the NT5E gene methylation was related to breast cancer development and associated with poor prognostic factors in breast cancer. Our results suggest that the NT5E gene methylation has potential as an epigenetic biomarker in breast cancer.

Prognostic Factors in Early-Stage Leiomyosarcoma of the Uterus

2009 ◽  
Vol 19 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Manuela Pelmus ◽  
Frédérique Penault-Llorca ◽  
Louis Guillou ◽  
Françoise Collin ◽  
Gérard Bertrand ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Vascular Invasion ◽  
Early Stage ◽  
Prognostic Significance ◽  
Figo Stage ◽  
Stage I ◽  
Free Interval ◽  
Important Prognostic Factor ◽  
Pathologic Features

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 × 10−15). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

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