scholarly journals The Impact of IDH1 Mutation and MGMT Promoter Methylation on Recurrence-Free Interval in Glioblastoma Patients Treated With Radiotherapy and Chemotherapeutic Agents

2021 ◽  
Vol 27 ◽  
Author(s):  
Maher Kurdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa ◽  
Badrah Alghamdi ◽  
Yazid Maghrabi ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Tumor Recurrence ◽  
Dna Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Idh1 Mutation ◽  
Treatment Modalities ◽  
Isocitrate Dehydrogenase 1 ◽  
Free Interval ◽  
Significant Difference ◽  
The Impact

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

scholarly journals The Potential Effect of the IDH1 Mutation and MGMT Gene Promotor Methylation on the Control of Glioblastoma-Associated Epilepsy in Patients Receiving Anti-Epileptic Agents and Chemotherapies

2021 ◽  
Author(s):  
Maher Kurdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa ◽  
Badrah Alghamdi ◽  
Yazid Maghrabi ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Dna Methyltransferase ◽  
Seizure Control ◽  
Potential Effect ◽  
Idh1 Mutation ◽  
Recurrence Interval ◽  
Effective Control ◽  
Isocitrate Dehydrogenase 1 ◽  
Methylguanine Dna Methyltransferase ◽  
Anti Epileptic Drug

Abstract Objective: (a) To assess the control of glioblastoma-associated seizure in patients receiving different anti-epileptic drugs and chemotherapies after total resection and its association with O-methylguanine-DNA methyltransferase (MGMT) promotor methylation and the isocitrate dehydrogenase 1 (IDH1) mutation; (b) to determine which anti-epileptic drug exerts the best effective control on glioblastoma-associated epilepsy; (c) to identify the relationship between seizure control and different anti-epileptic drugs and recurrence interval. Methods: This was a retrospective cohort study of patients with postoperative glioblastoma-associated epilepsy in the period between 2014 and 2019. The correlations between the IDH1 mutation and MGMT promotor methylation with anti-epileptic drugs, chemotherapy type, seizure control, and recurrence interval were analyzed using different statistical methods. Results: This study included 53 adult patients with glioblastoma-associated epilepsy. The IDH1 mutation was present in 20 patients, and MGMT promotor methylation was present in 13 patients. Out of 53 patients, 37 cases received chemoradiotherapy while 16 cases receive only radiotherapy. Levetiracetam was the most prescribed anti-epileptic drug (n= 36, 60%), and 36 and 16 patients had controlled and uncontrolled seizures, respectively. The IDH1 mutation and unmethylated MGMT promotor were significantly present in cases with controlled epilepsy (P < 0.05). Among the anti-epileptic drugs, levetiracetam showed significantly better seizure control in cases with the IDH1 mutation and unmethylated MGMT promotor (P < 0.05). Patients did not show significant differences in either seizure control or the tumor recurrence interval (P > 0.05).Conclusion: (a) Glioblastoma-associated epilepsy can be better controlled in patients with the IDH1 mutation and unmethylated MGMT promotor compared with patients with the methylated MGMT promotor, (b) Levetiracetam is considered the first-line anti-epileptic drug for controlling seizures but may not enhance the sensitivity of glioblastomas to chemotherapies, (c) Lack of seizure control in glioblastoma patients may not be related to tumor recurrence despite one-year treatment with anti-epileptic drugs, (d) Better understanding of the risk factors and mechanisms associated with glioma-associated epilepsy are needed to improve patient quality of life.

scholarly journals Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies

2021 ◽  
Vol 152 (3) ◽  
pp. 541-549
Author(s):  
Maher Kurdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa ◽  
Badrah Alghamdi ◽  
Yazid Maghrabi ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Recurrence Interval ◽  
Mgmt Methylation ◽  
Conventional Radiotherapy ◽  
Methylguanine Dna Methyltransferase ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Temozolomide Chemotherapy

Abstract Objective To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. Method We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. Results No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. Conclusion Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Hemangiogenic response after pre-operative COX2 inhibition predicts recurrence in esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15077-15077
Author(s):  
D. Jin ◽  
J. L. Port ◽  
P. Lee ◽  
L. Zhang ◽  
C. A. Ferrara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Tumor Recurrence ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Angiogenic Activity ◽  
Angiogenic Therapy ◽  
Men 2 ◽  
Promising Tool ◽  
Significant Difference ◽  
The Impact

15077 Background: Growth of esophageal cancer involves a proliferative hemangiogenic component. Biomarkers that predict this propensity in esophageal cancer and the impact of anti-angiogenic strategy on their levels as well as clinical response remain unknown. Methods: A multimodular approach was devised to assess hemangiogenic parameters in a cohort of chemotherapy naïve patients with locally advanced (T2-T3N0, T1-T3N1M0M1a) esophageal cancer pre- and 4 days post-celecoxib neoadjuvant treatment. Patients went on to receive neoadjuvant therapy with celecoxib, paclitaxel and carboplatin for 3 cycles, followed by surgical resection. This bioassay panel consists of 5 components: i) HUVEC-based angiogenic scale for functional plasma angiogenic activity, ii) flow cytometry to quantify CD133+VEGFR2+ circulating endothelial progenitors (CEPs), iii) hematopoietic colony-forming assay to quantify circulating hematopoietic progenitors (CHPs), iv) plasma SDF-1 level, and v) platelet VEGF-A level. Results: The cohort consists of 8 consecutive patients (6 men, 2 women) with median age of 58. After 18 months of followup, 6 patients remained alive and without evidence of recurrence, while 2 had tumor recurrence and metastasis. Analysis of the positive responders (pre-celecoxib baseline versus 4 days post treatment) revealed a global suppression of hemangiogenic parameters with reduction of the functional HUVEC-based angiogenic scale (mean score of 3.3 versus 1.8; p<0.05), 2.2-fold decrease in CEPs (p<0.05), and 3-fold decrease in CHPs (p<0.05). This trend also correlated with decreased plasma SDF-1 and platelet VEGF-A levels . However, in the 2 cases of tumor recurrence, the initial hemangiogenic response was blunted with no significant difference in all parameters tested during the celecoxib monotherapy period. Conclusion: Esophageal cancer development involved a hemangiogenic switch toward increased CEPs, CHPs, and functional plasma pro-angiogenic activity. COX2 inhibition with celecoxib normalized the hemangiogenic profile. Collective assessment of hemangiogenic biomarkers during neoadjuvant setting may be a promising tool in predicting clinical outcomes, recurrence, and for validating impact of anti-angiogenic therapy on esophageal cancer. No significant financial relationships to disclose.

Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method

2019 ◽  
Vol 73 (2) ◽  
pp. 112-115 ◽  
Author(s):  
Charlotte von Rosenstiel ◽  
Benedikt Wiestler ◽  
Bernhard Haller ◽  
Friederike Schmidt-Graf ◽  
Jens Gempt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Promoter Region ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Newly Diagnosed ◽  
Quantitative Level ◽  
Mgmt Promoter ◽  
The Impact

AimsO(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off.Methods67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria.ResultsMedian overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012).ConclusionThe results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and relation to 1p/19q loss in low grade gliomas: A GICNO study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20064-20064 ◽  
Author(s):  
L. Nicolardi ◽  
R. Bertorelle ◽  
L. Bonaldi ◽  
A. Compostella ◽  
A. Roma ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Alkylating Agents ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Low Grade ◽  
Tumor Localization ◽  
Response To Chemotherapy ◽  
Mgmt Promoter ◽  
The Impact

20064 Background: 1p and 19q deletions have been associated with a favorable response to chemotherapy and a good prognosis in patients (pts) with oligodendroglioma. MGMT promoter methylation has been associated with a longer survival in pts with glioblastoma who receive alkylating agents. As yet, there are no data on the expression of MGMT, and on the relationship between 1p/19q deletions and MGMT promoter methylation in low grade glioma (LGG). Methods: Pts that received a first line chemotherapy regimen with temozolomide for progressive LGG were enrolled in the study, designed to investigate the correlation between MGMT methylation status and 1p/19q deletions in this setting. 1p/19q deletions were analysed by FISH, and MGMT promoter methylation by methylation specific PCR (MSP). Results: Seventy-five pts (26 females, 49 males; median age 42 years: range 22–68 years) were accrued. Of these, 48 (64%) had oligodendrogliomas (O), 19 (25.3%) astrocytomas (A), and 8 (10.6%) oligoastrocytomas (OA); 44 (58.7%) had a history of epilepsy, 41 (54.7%) had a frontal tumor localization, 27 (36%) had MRI contrast enhancing lesions, and 35 (46.7%) had been pre-treated with radiotherapy. 1p/19q deletions, evaluable in 58 pts (77.3%), were both present in 36 pts (62%), (3 being A and 2 OA); 18 pts (31%) had no loss; 1 pt (1.7%) had 1p loss; 3 pts (5.2%) 19q loss. Combined 1p and 19q loss was not correlated with a frontal localization (p = 0.12), median age (0.47) and/or gender (0.62). MGMT promoter methylation, present in 17 (56.6%) of 30 assessable cases, was significantly associated with combined 1p/19q deletions (p = 0.03). MGMT promoter methylation was not significantly associated with age (p = 0.46), gender (p = 0.2), tumor localization (p = 0.12) and/or histology (0.37). Conclusions: 1p/19q deletions are strictly correlated to histology and to MGMT promoter methylation; further prospective trials are required to clarify the impact of these molecular signatures on clinical outcome. No significant financial relationships to disclose.

Is bridging therapy still required in stroke due to carotid artery terminus occlusions?

2017 ◽  
Vol 10 (7) ◽  
pp. 625-628 ◽  
Author(s):  
Romain Bourcier ◽  
Pierre-Louis Alexandre ◽  
François Eugène ◽  
Béatrice Delasalle-Guyomarch ◽  
Benoit Guillon ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Clinical Outcomes ◽  
Demographic Data ◽  
Intravenous Thrombolysis ◽  
Median Number ◽  
Treatment Modalities ◽  
Bridging Therapy ◽  
Stroke Treatment ◽  
Significant Difference ◽  
The Impact

IntroductionStudies comparing endovascular stroke treatment using mechanical thrombectomy (MT) with or without prior IV tissue plasminogen activator (tPa) have included only 30% of internal carotid artery terminus occlusions (ICA-O), a known predictor of recanalization failure with IV tPa.ObjectiveTo carry out a retrospective multicenter analysis of prospectively collected data of consecutive patients to investigate the impact of intravenous thrombolysis on ICA-O by comparing patients treated with MT alone or bridging therapy (BT).Material and methodsPatients with ICA-O treated with MT alone or BT were retrospectively examined and compared. Demographic data, vascular risk factors, treatment modalities, complications, technical and clinical outcomes were recorded. A propensity score (PS) analysis was used to compare modified Rankin Scale (mRS) score at 3 months and intracerebral hemorrhage (ICH) between groups.Results141 consecutive patients (60% BT/40% MT) were included between January 2014 and June 2016. Baseline characteristics did not differ between the groups. There was no significant difference in the rate of Thrombolysis in Cerebral Infarction 2b/3, distal emboli, and median number of passes between the groups. There was a significant difference between BT and MT groups in the median time between imaging and groin puncture (median 97 min vs 75, p=0.007), the rate of ICH (44% vs 27%, p=0.05), but not for symptomatic ICH (18% vs 13%, p=0.49). With PS, there was a trend towards a higher rate of ICH (OR=2.3, 95% CI 0.9 to 5.9, p=0.09) in the BT group compared with the MT alone group, with no difference in mRS score ≤2 at 3 months (OR=1.6, 95% CI 0.7 to 3.7, p=0.29).ConclusionThere was no significant difference in clinical outcomes between patients receiving bridging therapy versus direct thrombectomy. Bridging therapy delayed time to groin puncture and increased ICH rate.

scholarly journals The Impact of Epigenetic Modifications in Myeloid Malignancies

2021 ◽  
Vol 22 (9) ◽  
pp. 5013
Author(s):  
Deirdra Venney ◽  
Adone Mohd-Sarip ◽  
Ken I Mills
Keyword(s):  
Disease Progression ◽  
Dna Methyltransferase ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Isocitrate Dehydrogenase 1 ◽  
Myeloid Malignancies ◽  
Broad Term ◽  
Critical Components ◽  
The Impact

Myeloid malignancy is a broad term encapsulating myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Initial studies into genomic profiles of these diseases have shown 2000 somatic mutations prevalent across the spectrum of myeloid blood disorders. Epigenetic mutations are emerging as critical components of disease progression, with mutations in genes controlling chromatin regulation and methylation/acetylation status. Genes such as DNA methyltransferase 3A (DNMT3A), ten eleven translocation methylcytosine dioxygenase 2 (TET2), additional sex combs-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and isocitrate dehydrogenase 1/2 (IDH1/2) show functional impact in disease pathogenesis. In this review we discuss how current knowledge relating to disease progression, mutational profile and therapeutic potential is progressing and increasing understanding of myeloid malignancies.

scholarly journals A SIMPLE SCREENING PROCEDURE COULD IDENTIFY INDIAN PATIENTS WITH EARLY COGNITIVE IMPAIRMENT AND ITS IMPLICATIONS FOR THE MANAGEMENT OF GERIATRIC HIP FRACTURES

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Mrudev Gandhi ◽  
Utsav Patel
Keyword(s):  
Cognitive Impairment ◽  
Hip Fracture ◽  
Hip Fractures ◽  
Treatment Modalities ◽  
Wide Range ◽  
Significant Difference ◽  
Male Preponderance ◽  
Geriatric Hip Fracture ◽  
Asymptomatic Phase ◽  
The Impact

Background: Dementia is one of the most common and cognitive impairments growing over the globe. It encompasses a wide range of other neurodegenerative disorders with the symptoms such as loss of memory, inability in carrying out everyday activities, a decline in the brain function activities, and perplexity. However, it has been identified that there is an absolute lack of treatment modalities for dementia, but the early diagnosis plays an important role in identifying the cognitive impairment in the asymptomatic phase itself. It helps in preventing the disease from reaching a further complicated stage Aim: To assess the impact of cognitive impairment screening on the management of geriatric hip fractures Methods: It was an observational study carried out at Shree Krishna Hospital, Karamsad; for a period of two years (June 2018 to May 2020). Two hundred sixty patients were included in the study. The patients were divided into three groups, namely hemiarthroplasty (HA), Total Hip Arthroplasty (THA), hemiarthroplasty in patients with known dementia (HAd). Result: The study showed male preponderance in the study, and the majority of the patients were above 80 years of age. There was a significant difference in the patients who can perform their grocery or medication independently and not independently with respect to MMSE. However, there was no statistically significant difference in Hip Harris Score. There was a statistically significant difference among the three groups regarding the intraoperative blood, operation duration, hospital stay, ICU postoperative, in-hospital details. Conclusion: In light of the above literature, it was found that hip fractures and cognitive impairment were closely related. There are many risk factors of hip fracture, which are aggravated due to the late diagnosis of cognitive impairment. The incidence of hip fracture among patients suffering from dementia was much higher as compared to normal patients. Keywords: multi-morbidity, cognitive impairment, geriatric hip fracture

Sexuality and fertility in long-term survivors of testicular cancer.

1997 ◽  
Vol 15 (4) ◽  
pp. 1444-1448 ◽  
Author(s):  
Y Arai ◽  
M Kawakita ◽  
Y Okada ◽  
O Yoshida
Keyword(s):  
Sexual Dysfunction ◽  
Testicular Cancer ◽  
Treatment Modalities ◽  
Retroperitoneal Lymph Node Dissection ◽  
Treatment Groups ◽  
Significant Difference ◽  
Chemotherapy Patients ◽  
The Impact ◽  
Long Term Survivors

PURPOSE We assessed the impact of different treatment modalities on sexuality and fertility in long-term survivors of testicular cancer. MATERIALS AND METHODS The sample consisted of 85 testicular cancer patients, of whom 19 had undergone chemotherapy with retroperitoneal lymph node dissection (RPLND), 15 had received chemotherapy only, 42 had received infradiaphragmatic radiotherapy, and nine had received surveillance therapy. The questionnaire reported sexual function, marital status, and issues related to fertility and childbearing. RESULTS One fourth to one half reported some type of sexual impairment in each group. The only significant difference was that approximately 70% of men with RPLND reported inability of ejaculation and a greater decline in semen volume, which is expected. The most striking finding is that the rates and nature of sexual dysfunction of surveillance patients were similar to other treatment groups, except for ejaculatory function. The highest rates of infertility distress were observed in chemotherapy patients. CONCLUSION These data suggest that sexual dysfunction and infertility represent the major persisting side effects, even years after diagnosis. The hypothesis that surveillance patients have fewer sexual problems is not upheld in this study.

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