RADT-09. ROLE OF RADIOTHERAPY IN MANAGEMENT OF PRIMARY SPINAL HIGH GRADE GLIOMA: A SINGLE INSTITUTION RETROSPECTIVE ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi42-vi43
Author(s):  
Rituraj Upadhyay ◽  
Swapnil Khose ◽  
Halyna Pokhylevych ◽  
Arnold dela Cruz Paulino ◽  
Mary Frances McAleer ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Univariate Analysis ◽  
Concurrent Chemotherapy ◽  
Leptomeningeal Disease ◽  
High Grade ◽  
Single Institution ◽  
Who Grade ◽  
Mgmt Promoter ◽  
High Grade Gliomas ◽  
H3k27m Mutation

Abstract BACKGROUND Primary spinal high-grade gliomas(S-HGG) are rare, aggressive tumors and radiation therapy(RT) plays a dominant role in the management given their infiltrative nature. We conducted a single-institution retrospective review to study the clinicopathological features and management of S-HGGs. METHODS Patients with biopsy-proven S-HGG who received RT from 2001-2020 were analyzed for patient, tumor, and treatment characteristics. Kaplan-Meier estimate and Cox proportional hazard regression method were used for survival analyses. RESULTS Twenty-nine patients were identified with a median age of 25.9 years (range 1-74y). Four patients had gross total resection(GTR) while 25 underwent subtotal resection or biopsy. Nineteen patients had WHO grade 4 tumor. IDH1 mutation and MGMT promoter methylation were analyzed in 14 and four patients respectively; all were IDH wildtype and MGMT-promoter unmethylated. H3K27M mutation was present in five out of 10 patients tested. Twenty-two patients received photon-based radiation and 7 received proton therapy. Median RT dose was 50.4 Gy (range 39.6-54Gy) with 79% receiving >45Gy. 65% patients received concurrent chemotherapy, most commonly temozolomide. Twenty-three (79%) patients had documented recurrence. Overall, 16 patients relapsed locally, 10 relapsed in the brain and 8 developed leptomeningeal disease; only 8(35%) had isolated local relapse. Median OS from diagnosis was 21.3 months and median PFS after RT was 9.7 months. On univariate analysis, age, sex, GTR, grade, RT modality, RT dose and concurrent chemotherapy did not predict for survival. Patients with H3K27M mutation had a poorer median PFS after RT compared to those without the mutation but the difference did not reach statistical significance (p = 0.26). CONCLUSIONS Although 86% of patients had gross disease at RT and received a lower median RT dose than typically used in cerebral high-grade gliomas, only 55% of patients failed locally. H3K27M mutation may portend worse survival; future studies to improve the therapeutic approach in these patients are warranted.

Timing of re-irradiation in recurrent high-grade gliomas: a single institution study

2018 ◽  
Vol 138 (3) ◽  
pp. 571-579 ◽  
Author(s):  
A. Zemlin ◽  
B. Märtens ◽  
B. Wiese ◽  
R. Merten ◽  
D. Steinmann
Keyword(s):  
High Grade ◽  
Single Institution ◽  
High Grade Gliomas

An analysis of two different schedules of radiochemotherapy with concomitant temozolomide in high grade gliomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2035-2035 ◽  
Author(s):  
G. R. D’Agostino ◽  
M. Balducci ◽  
C. Anile ◽  
S. Manfrida ◽  
G. Di Lella ◽  
...  
Keyword(s):  
Overall Survival ◽  
Statistical Significance ◽  
Residual Tumor ◽  
Hematological Toxicity ◽  
High Grade ◽  
Safe Alternative ◽  
Neurological Toxicity ◽  
Tumor Bed ◽  
Historical Series ◽  
High Grade Gliomas

2035 Background: We compared two different schedules of temozolomide (TMZ) concomitant therapy in terms of toxicity and outcome. Methods: 70 patients (median age 61 years, range 27–80) affected by high grade gliomas were treated with concomitant chemoradiation. Conformal radiotherapy (5,940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3,960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1,980 cGy) was associated with one of the following TMZ schedules: TMZ1: (75 mg/m2 × 5 days, first and last week of radiotherapy); TMZ2 (75 mg/m2, 7 days/week, from the first to the last day of radiotherapy); Toxicities were graded according to RTOG criteria. Survival analysis based on the Kaplan-Meier model. Results: From October, 2000 to March, 2006, 54 patients high grade gliomas were evaluated. 41 patients (29 GBL, 70.7%; 12 AA, 29.3%) were treated between October 2003 and March 2006 with TMZ2, and compared to an historical series of 29 patients (25 GBL, 86.2%; 4 AA, 13.%) treated in our Institution before 2003 with TMZ1. All patients received adjuvant chemotherapy with TMZ for 6 cycles or until disease progression. Hematological toxicity was mild in both group, whereas neurological toxicity (seizures) was higher in TMZ2 group, with a grade > 2 toxicity registered in 11/41 pts (26.8%) compared to 1/29 of the TMZ1 group (3.5%), even if this difference failed to achieve statistical significance (p=0.06). The overall survival did not significantly differ among the 2 schedules (p=0.60). In fact, at a median follow-up of 21 months (range 3- 68), median survival time was 21 months and 19 months, for TMZ1 and TMZ2 groups, respectively, with a 1-year and 2-year overall survival of 73.1% in the TMZ1 group and 75.3% in the TMZ2 group, respectively. Conclusions: In our experience, the concomitant administration of TMZ at the daily dose of 75 mg/m2 given continuously or only in the first and the last week of radiotherapy obtained comparable results in terms of outcome, with a heavier neurological toxicity when given 7 days per week, from the first to the last day of radiotherapy. These data suggest that, in selected cases, the TMZ1 schedule can be considered as a safe, alternative strategy, which does not impact significantly on patient outcome, compared to the standard TMZ2. No significant financial relationships to disclose.

scholarly journals Potential CanonicalWntPathway Activation in High-Grade Astrocytomas

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca Schüle ◽  
Christine Dictus ◽  
Benito Campos ◽  
Feng Wan ◽  
Jörg Felsberg ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Luciferase Reporter ◽  
High Grade ◽  
Luciferase Reporter Gene ◽  
Protein Truncation Test ◽  
Who Grade ◽  
Transcriptional Cofactors ◽  
Pathway Activation ◽  
Gene Assay ◽  
High Grade Gliomas

Aberrantwntpathway activation through cytoplasmic stabilization ofβ-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e.,β-catenin-dependent) signalling is largely unknown. Here, we studied canonicalwntpathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmicβ-catenin accumulation. Furthermore, we assessed the prognostic relevance ofβ-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression ofβ-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3βand APC, constituents of theβ-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmicβ-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations ofβ-catenin and APC leading to cytoplasmic stabilization ofβ-catenin were excluded by direct sequencing or protein truncation test. In patient tissues,β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increasedβ-catenin expression and lowβ-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonicalwntpathway activation in high-grade gliomas and demonstrate thatβ-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome.

scholarly journals Relación Entre El Coeficiente De Difusión Aparente y la celularidad. [Relación Entre El Coeficiente De Difusión Aparente yLa Celularidad De Gliomas en Centro de tercer nivel de Panamá]

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
José María Barría Castro ◽  
Linamar Antuaneth Caballero Vega ◽  
Javier Augusto Pimentel Sández ◽  
Fernando Miguel Sucre Grimaldo
Keyword(s):  
Magnetic Resonance ◽  
Malignant Tumors ◽  
Histological Grade ◽  
Statistical Significance ◽  
Region Of Interest ◽  
Low Grade ◽  
High Grade ◽  
Anatomic Site ◽  
Adc Values ◽  
High Grade Gliomas

<p>Resumen<br /><br />Introducción: Los gliomas son tumores malignos altamente celulares del sistema nervioso central. Su grado histológico preoperatorio es de utilidad en el manejo quirúrgico, por lo que la resonancia magnética con secuencias avanzadas intenta brindar mayor información tumoral.  <br />Objetivo: Relacionar el coeficiente aparente de difusión (CAD) y celularidad de los gliomas de pacientes entre enero 2015 a diciembre 2017.</p><p><br />Metodología:Retrospectivamente se obtuvieron de archivos clínicos la edad, sexo, tipo, grado histológicoy sitio anatómico. Se calculó el CAD en 5mm2 en los estudios de resonancia magnética preoperatorias y se utilizó las laminillas para conteo de celularidad en 5mm2 digitalmente. Se utilizó análisis estadísticos descriptivos y coeficiente de correlación entre CDA con celularidad. Se utilizaron valores de p &lt; 0.05 para significancia estadística.<br />Resultados: 46 casos fueron incluidos, 56.5% fueron hombres. El rango de 41-64 años fueron los más afectados. El glioblastoma fue el tipo histológico más frecuente (47.8%), así como los gliomas de alto grado (73.9%). El 95.7% fueron supratentoriales. La celularidad promedio fue de 3970 ± 2900 vs 2436 ± 948 núcleos/5mm2 (p = 0.13), con valores promedio de CDA mínimo de 0.813 x 10-3 ± 0.229 mm2/s vs 1.052 x 10-3 ± 0.196 mm2/s (p = 0.002), para los gliomas de alto y bajo grado respectivamente. La correlación entre CDA y celularidad fue débil (R = - 0.13, p = 0.37).</p><p><br />Conclusión: Existe correlación débil inversamente proporcional entre el CDA y la celularidad con distinción de gliomas de bajo y alto grado con valores de CDA mínimos.<br /><br /> <br />Abstract<br />Introduction: Gliomas are highly cellular malignant tumors of the central nervous system. Itspreoperative histological grade is useful in surgical management,so magnetic resonance imaging with advanced sequences tries to provide more tumor information.</p><p><br />Objective:Correlateapparent diffusion coefficient (ADC) and cellularity of gliomas of patients between January 2015 to December 2017.<br />Methodology:Data of age, sex, type, histologic grade and anatomic site were retrospectively obtained from clinical archives.The preoperative magnetic resonance ADC was calculated in a 5 mm2 region of interest and the microscope slides were used for the cellularity digitally count in 5 mm2. Descriptive statistical analysis and correlation coefficient between ADC and cellularity were used. Values of p &lt;0.05 were used for statistical significance.</p><p><br />Results: 46 cases were included, 56.5% were men. The 41-64 years ranges were the most affected. Glioblastoma was the most frequent histological type (47.8%), as well as high grade gliomas (73.9%). 95.7% were supratentorial. The average cellularity was 3970 ± 2900 vs 2436 ± 948 nuclei/ 5mm2 (p = 0.13), with average minimum ADC values of 0.813 x 10-3 ± 0.229 mm2/s vs 1052 x 10-3 ± 0.196 mm2/s (p = 0.002), for high- and low-grade gliomas, respectively. The correlation between ADC and cellularity was weak (R = - 0.13, p = 0.37).</p><p><br />Conclusions:There is a weak inversely proportional correlation between ADC and cellularity. With distinction of low- and high-grade gliomas with minimum ADC values.<br /><br /></p>

Significance of H3K27M Mutation in "Nonmidline" High-Grade Gliomas of Cerebral Hemispheres

2019 ◽  
Vol 131 ◽  
pp. 174-176 ◽  
Author(s):  
Giuseppe La Rocca ◽  
Giovanni Sabatino ◽  
Roberto Altieri ◽  
Francesco Signorelli ◽  
Luca Ricciardi ◽  
...  
Keyword(s):  
Cerebral Hemispheres ◽  
High Grade ◽  
High Grade Gliomas ◽  
H3k27m Mutation

Effect of temozolomide chronotherapy in patients with high-grade glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14525-e14525 ◽  
Author(s):  
Himachandana Atluri ◽  
Jian Li Campian ◽  
Grayson Talcott ◽  
Melissa Meyer ◽  
Emily Slat ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Biological Rhythms ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Well Being ◽  
Current Therapy ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Morning Administration

e14525 Background: High grade gliomas (HGG) (the most common being glioblastoma) are the most common primary CNS malignancy in adults. Mainstay of therapy is surgical resection followed by concurrent radiation and temozolomide (TMZ) followed by adjuvant TMZ. Unfortunately, prognosis remains poor and optimization of current therapy is critical. Chronotherapy is defined as improvement in treatment outcomes by maximizing treatment efficacy and minimizing toxicity by administering medications in accordance with biological rhythms of the patient. In a mouse model, there was greater anti-tumor efficacy during morning administration of TMZ. This trial was designed to determine the feasibility and potential clinical impact of chrono-therapeutically administering TMZ in patients with HGG. Methods: Adult patients ( > 18 years) with HGG (WHO Grade III/IV) were eligible. Patients were screened and consented prior to initiation of monthly TMZ therapy. Eligible patients were randomized to TMZ in the morning (AM) before 10AM or in the evening (PM) after 8PM. Pill diaries were recorded for drug administration time and compliance. Fact-Br Quality of Life (QoL) surveys were administered to patients at the time of enrollment in the trial and at the end of treatment to measure differences in QoL in both groups. Circadian rhythm was recorded by Actiwatch. Adverse events (AE), overall survival (OS) and progression free survival (PFS) were measured for each group. Results: At the time of submission, a total of 28 patients were evaluated. 15 patients were in AM group and 13 in PM group. It is feasible for participants to take TMZ per study assignment. There was no significant difference in the QoL based on the Fact-Br dataset in the four main categories of physical well-being, social/family well-being, functional well-being and emotional well-being. The Friedman’s two-way nonparametric ANOVA tests were used to analyze the differences across time points. Cytopenias are a known adverse effect of TMZ. There was a trend towards worsening lymphocyte counts in the AM group compared to PM group, although not statistically significant. There was no statistical significance in PFS or OS in patients with newly diagnosed glioblastoma. Conclusions: Chronotherapy with TMZ is feasible. A trend of worsening lymphocyte counts is noted in AM treatment group compared to PM group but was not statistically significant. No difference in OS or PFS was noted, although sample size was too small to effectively assess this. A larger study will need to be conducted to effectively assess the effect of chronotherapy on survival. Clinical trial information: NCT02781792.

Association of leukocyte count (neutrophilia and lymphopenia) with poor prognosis in patients with high-grade gliomas in a Guatemalan cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14500-e14500
Author(s):  
Rixci Ramirez ◽  
Daniel Estuardo Rosales Lopez ◽  
Jennifer Dominguez ◽  
Marisol Gramajo ◽  
Carolina Camey
Keyword(s):  
Overall Survival ◽  
Neutrophil Count ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Rank Test ◽  
Significant Prognostic Factor ◽  
High Grade ◽  
Initial Surgery ◽  
High Grade Gliomas ◽  
Clinical Records

e14500 Background: In previous studies separately, it has already been determined how the inflammatory response measured by it neutrophilia and also lymphopenia s with temozolamide have determined that they are important at the time of initiation of treatment and have a prognostic value in patients with high-grade gliomas, the objective This study was the prognostic value of leukocyte disorders, absolute neutrophil count and absolute lymphocyte count in a retrospective cohort of patients with high-grade glioma who receive concomitant temozolomide and radiation plus maintenance. Methods: Clinical records of patients treated at the Guatemalan Social Security Institute were registered in the Oncology service within the period from January 1, 2013 to December 2018, the treatment consisted of temozolomide (75 mg / m2 per day) and concomitant radiation and subsequent maintenance with temozolomide (150 mg / m2 D1-5) every 28 days for 6 cycles. The prognostic value of neutrophilia and lymphopenia, prior to treatment in survival, was defined as a neutrophil count greater than 7x10 3 / uL and lymphopenia less than 2 x10 3 / uL. The analysis was performed using Kapplan Mayer curves, log rank test and Cox analysis. Results: We identified 64 high-grade patients (grades III and IV according to WHO), all treatments with concomitant chemoradiotherapy based on temozolomide and subsequent maintenance with temozolamide. The initial surgery was lost in the majority (75%), with resection > 90% in 25 patients (34%). 79.4% were treated with radiotherapy plus concomitant chemotherapy followed by adjuvant chemotherapy with temozolamide of these, 69% completed the treatment, thirty-two patients (50%) with pre-treatment neutrophilia. The overall survival at 2 years was 55%. In the univariate analysis, neutrophilia is associated with a worse overall survival (p = 0.019), as well as lymphopenia (p = 0.003), in addition to the age ≥65 years (p = 0.0001), surgical resection < 90% (p = 0.045) and prednisolone consumption ≥50mg / day (p = 0.045). In the multivariate analysis, neutrophilia (p = 0.017), age ≥65 (p = 0.001), lymphopenia (p = 0.0056) were associated with a worse prognosis with reduced survival. Conclusions: In high-grade gliomas treated with temozolomide and concomitant radiation followed by maintenance with temozolamide, neutrophilia and lymphopenia can be a significant prognostic factor for overall survival, with the advantage that it is not an expensive test and is accessible at all times of patient follow-up.

DNA hydroxymethylation in high-grade gliomas

2021 ◽  
Author(s):  
Angelika Stapińska-Syniec ◽  
Marta Grabiec ◽  
Marcin Rylski ◽  
Albert Acewicz ◽  
Michał Sobstyl
Keyword(s):  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
High Grade ◽  
Who Grade ◽  
Dna Hydroxymethylation ◽  
Current State ◽  
Survival Estimation ◽  
High Grade Gliomas ◽  
Tet Enzymes

Background and Study Aims Since the new WHO classification of nervous system tumors (2016 revised 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that DNA methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis. In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grade III and IV). Results The correlation of DNA hydroxymethylation and survival in glioblastoma patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and Ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the control brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment. Conclusion Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help to develop new targeted therapies.

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