Download PDF
CC BY-NC-ND 4.0 · South Asian J Cancer 2024; 13(02): 146-149
DOI: 10.1055/s-0042-1759771
Original Article
Brain Tumour

Prognosis of MGMT-Positive Gene in Patients with Brain Tumors of Grade III and Grade IV

Ishitaa Rajendra
1   Department of Radiation Oncology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
Shikha Dhal
1   Department of Radiation Oncology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
Sumit Goyal
1   Department of Radiation Oncology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
Surabhi Tyagi
2   Department of Pathology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
B. S. Sharma
3   Department of Head Neurosurgery, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
Ajay Yadav
4   Department of Medical Oncology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
,
Dinesh Yadav
5   Department of Surgical Oncology, Sri Ram Cancer and Superspeciality Centre, Jaipur, Rajasthan, India
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Zoom Image
Sumit Goyal

Objective To evaluate MGMT gene positivity is associated with better survival in patients diagnosed with brain tumor World Health Organization (WHO) grades III and IV

Material and Methods Single-institute restrospective study. A total of 80 patients were enrolled, all underwent surgery either total or subtotal excision of the tumor and MGMT gene testing on tumor tissue by RT-PCR. All received adjuvant radiation (60 Gy/30 fractions, 5 fractions/week) with concurrent temozolomide (75 mg/m2), followed by 12 cycles of adjuvant temozolomide (150 mg/m2 1st cycle followed by 200 mg/m2) with regular follow-up.

Results A total of 80 patients, 75 underwent subtotal excision, 27 were WHO grade III vs. 48 WHO grade IV. Five underwent total excision 1 was WHO grade III vs. 4 WHO grade IV. The median PFS and OS in five patients in total excision in grade III patient was 9.0 and 20 compared with Grade IV, where the median PFS and OS was 8.8 and 17.8 months. Out of 75 patients in the subtotal group median PFS and OS, respectively, in Grade III group was 9.1 and 19.3 and, WHO grade IV with median PFS of 8.8 and OS of 18.8.

Conclusion MGMT gene positivity is a prognostic factor in grade III and IV brain tumor.

Keywords

brain tumor - excision - grade III and IV - MGMT - temozolomide


Publication History

Article published online:
02 March 2023

© 2023. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Zhang K, Wang XQ, Zhou B, Zhang L. The prognostic value of MGMT promoter methylation in glioblastoma multiforme: a meta-analysis. Fam Cancer 2013; 12 (03) 449-458
    CrossrefPubMedSearch in Google Scholar
  • 2 Louis DN, Perry A, Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
    CrossrefPubMedSearch in Google Scholar
  • 3 Halperin EC, Wazer DE, Perez CA, Brady LW. Principles and Practice of Radiation Oncology. 6th ed.. Wolters Kluwer/Lippincott Williams and Wilkins; 2013
    Search in Google Scholar
  • 4 Stupp R, Mason WP, van den Bent MJ. et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
    CrossrefPubMedSearch in Google Scholar
  • 5 Yu W, Zhang L, Wei Q, Shao A. O6-methylguanine-DNA methyltransferase (MGMT): challenges and new opportunities in glioma chemotherapy. Front Oncol 2020; 9: 1547
    CrossrefPubMedSearch in Google Scholar
  • 6 Hegi ME, Diserens AC, Gorlia T. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352 (10) 997-1003
    CrossrefPubMedSearch in Google Scholar
  • 7 Kruser TJ, Bosch WR, Badiyan SN. et al. NRG brain tumor specialists consensus guidelines for glioblastoma contouring. J Neurooncol 2019; 143 (01) 157-166
    CrossrefPubMedSearch in Google Scholar
  • 8 Armstrong TS, Cao Y, Scheurer ME. et al. Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro-oncol 2009; 11 (06) 825-832
    CrossrefPubMedSearch in Google Scholar
  • 9 Julie DAR, Ahmed Z, Karceski SC. et al. An overview of anti-epileptic therapy management of patients with malignant tumors of the brain undergoing radiation therapy. Seizure 2019; 70: 30-37
    CrossrefPubMedSearch in Google Scholar
  • 10 Hegi ME, Diserens AC, Godard S. et al. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004; 10 (06) 1871-1874
    CrossrefPubMedSearch in Google Scholar
  • 11 Karayan-Tapon L, Quillien V, Guilhot J. et al. Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 2010; 97 (03) 311-322
    CrossrefPubMedSearch in Google Scholar
  • 12 Sonoda Y, Yokosawa M, Saito R. et al. O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma. Int J Clin Oncol 2010; 15 (04) 352-358
    CrossrefPubMedSearch in Google Scholar
  • 13 Lechapt-Zalcman E, Levallet G, Dugué AE. et al. O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation and low MGMT-encoded protein expression as prognostic markers in glioblastoma patients treated with biodegradable carmustine wafer implants after initial surgery followed by radiotherapy with concomitant and adjuvant temozolomide. Cancer 2012; 118 (18) 4545-4554
    CrossrefPubMedSearch in Google Scholar
  • 14 Kim YS, Kim SH, Cho J. et al. MGMT gene promoter methylation as a potent prognostic factor in glioblastoma treated with temozolomide-based chemoradiotherapy: a single-institution study. Int J Radiat Oncol Biol Phys 2012; 84 (03) 661-667
    CrossrefPubMedSearch in Google Scholar
  • 15 Costa BM, Caeiro C, Guimarães I. et al. Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study. Oncol Rep 2010; 23 (06) 1655-1662
    PubMedSearch in Google Scholar
  • 16 Christians A, Hartmann C, Benner A. et al. Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma. PLoS One 2012; 7 (03) e33449
    CrossrefPubMedSearch in Google Scholar
  • 17 Morandi L, Franceschi E, de Biase D. et al. Promoter methylation analysis of O6-methylguanine-DNA methyltransferase in glioblastoma: detection by locked nucleic acid based quantitative PCR using an imprinted gene (SNURF) as a reference. BMC Cancer 2010; 10: 48
    CrossrefPubMedSearch in Google Scholar
  • 18 Balańa C, Carrato C, Ramírez JL. et al. Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients. Clin Transl Oncol 2011; 13 (09) 677-685
    CrossrefPubMedSearch in Google Scholar
  • 19 Ellingson BM, Cloughesy TF, Pope WB. et al. Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. Neuroimage 2012; 59 (02) 908-916
    CrossrefPubMedSearch in Google Scholar
  • 20 Lakomy R, Sana J, Hankeova S. et al. MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci 2011; 102 (12) 2186-2190
    CrossrefPubMedSearch in Google Scholar
  • 21 van den Bent MJ, Tesileanu CMS, Wick W. et al. Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol 2021; 22 (06) 813-823
    CrossrefPubMedSearch in Google Scholar
  • 22 Mansouri A, Hachem LD, Mansouri S. et al. MGMT promoter methylation status testing to guide therapy for glioblastoma: refining the approach based on emerging evidence and current challenges. Neuro-oncol 2019; 21 (02) 167-178
    CrossrefPubMedSearch in Google Scholar
  • 23 Cankovic M, Mikkelsen T, Rosenblum ML, Zarbo RJ. A simplified laboratory validated assay for MGMT promoter hypermethylation analysis of glioma specimens from formalin-fixed paraffin-embedded tissue. Lab Invest 2007; 87 (04) 392-397
    CrossrefPubMedSearch in Google Scholar