MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series

Case Series

Ann Hematol Onco. 2023; 10(2): 1421.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series

Jonathan Lee1; Rimas V Lukas2,3; Ignacio Jusue-Torres1; Anand V Germanwala1,4,5; Ewa Borys6; Abhishek A Solanki7; Atul K Mallik8; Kevin Barton9; Jigisha P Thakkar 1,10

1Department of Neurological Surgery, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

2Department of Neurology, Northwestern University, USA

3Lou & Jean Malnati Brain Tumor institute of the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

4Department of Otolaryngology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

5Department of Neurological Surgery, Edward Hines, Jr. VA Hospital, Hines, IL, USA

6Department of Pathology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

7Department of Radiation Oncology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

8Department of Radiology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

9Department of Hemato-oncology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

10Department of Neurology, Loyola University Medical Center/Stritch School of Medicine, Maywood, IL, USA

*Corresponding author: Jigisha P Thakkar Loyola University Stritch School of Medicine, Department of Neurology and Neurosurgery, Division of Neuro-oncology, USA. Email: jigisha.thakkar@lumc.edu

Received: March 07, 2023 Accepted: April 22, 2023 Published: April 29, 2023

Abstract

We present three cases of O6-Methylguanine-DNA Methyltransferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Keywords: Distant recurrence; High grade glioma; MGMT methylated

Highlights

• Patients with positive MGMT promoter methylation status may have a higher rate of distant recurrence and survival is significantly shorter post-recurrence in patients with distal recurrence.

• The original tumor site was stable when distant recurrence occurred, indicating good local control with Stupp protocol in MGMT methylated tumors.

• The original tumor and distant tumor may harbor many of the same truncal mutations.

• However, the distant tumor may accumulate additional mutations which could be contributing factors to its spread.

Introduction

MGMT methylated high grade gliomas have better response to treatment and better survival as compared to MGMT unmethylated gliomas [1]. Distant recurrence is more common in MGMT methylated tumors [2]. We present a series of three cases of MGMT methylated gliomas with distant recurrence who had poor outcomes despite the MGMT methylated status. All these patients had stable original tumor site when distant recurrence occurred. This observation indicates good local control in MGMT methylated high grade glioma with current standard treatment. However, standard treatment fails to prevent distant recurrence and therapeutic strategies to prevent distant recurrence are warranted in selected MGMT methylated patients.

Cases

Patient 1

A sixty-five years old female was diagnosed with glioblastoma World Health Organization (WHO) grade 4, Isocitrate Dehydrogenase Enzyme (IDH) wild type (WT), MGMT methylated. She underwent complete resection of the left frontal tumor followed by treatment with Stupp protocol (concomitant temozolomide + radiation sixty gray x thirty fractions followed by six cycles of maintenance temozolomide. Postoperative ischemic volume was <1ml. Surveillance imaging one-year after initial surgery (four months post completion of Stupp protocol) revealed stable postoperative surgical cavity with development of a new remote rim-enhancing left temporal mass (Figure 1). She underwent re-resection with pathology revealing glioblastoma, IDH-WT, MGMT methylated with increased tumor mutational burden when compared with initial pathology. She was initiated on concurrent temozolomide and radiation for the recurrent tumor. However, her clinical course was complicated by perforated diverticulitis requiring hospitalization. She had significant deterioration in her functional status and the family opted to transition to hospice care (two months after second craniotomy).