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Multicenter Study
. 2025 Apr;14(8):e70689.
doi: 10.1002/cam4.70689.

Temporal Muscle Thickness as a Prognostic Marker in a Real-Life Cohort of Newly Diagnosed MGMT Promoter Methylated Glioblastoma: A Multicentric Imaging Analysis

Lazaros Lazaridis  1   2   3 , Christoph Moenninghoff  4 , Elisabeth Bumes  5 , Dorothee Cäcilia Spille  6 , Michael Müther  6 , Tim Schulz  7 , Sina Heider  8 , Sarina Agkatsev  1   2   3 , Teresa Schmidt  1   2 , Tobias Blau  2   9   10 , Christoph Oster  1   2   10 , Walter Stummer  6 , Almuth Friederike Kessler  7 , Clemens Seidel  8 , Oliver Grauer  11 , Peter Hau  5 , Yahya Ahmadipour  2   12 , Ulrich Sure  2   12 , Kathy Keyvani  2   9 , Ulrich Herrlinger  13 , Christoph Kleinschnitz  1   2 , Martin Stuschke  2   14 , Nika Guberina  2   14 , Ken Herrmann  2   15 , Cornelius Deuschl  2   16 , Björn Scheffler  10 , Sied Kebir  1   2   10 , Martin Glas  1   2   10   13   17
Affiliations
Multicenter Study

Temporal Muscle Thickness as a Prognostic Marker in a Real-Life Cohort of Newly Diagnosed MGMT Promoter Methylated Glioblastoma: A Multicentric Imaging Analysis

Lazaros Lazaridis et al. Cancer Med. 2025 Apr.

Abstract

Introduction: Prior research has identified temporal muscle thickness (TMT) as a prognostic marker in glioblastoma. Nonetheless, implementation in daily clinical practice is complicated due to the heterogeneity of previous studies. We performed a multicentric analysis aiming to validate recently proposed sex-specific cutoff values using a homogeneous cohort of newly diagnosed MGMT promoter methylated glioblastoma patients; we included a balanced control cohort for comparison.

Materials and methods: TMT was measured at baseline using the initial preoperative/postoperative magnetic resonance images (MRIs) and in disease course using the first MRI after radiotherapy. Patients were divided by sex and TMT into "at risk of sarcopenia" or "normal muscle status." Kaplan-Meier and multivariable Cox regression analysis was used for survival correlation.

Results: In total, n = 126 patients were included (n = 66 treated with CCNU/temozolomide, n = 60 with single-drug temozolomide). Patients with normal muscle mass at baseline had significantly prolonged survival (median overall survival: 44.2 months versus 16.7 months with CCNU/temozolomide, and 29.5 months versus 17.4 months with single-drug temozolomide) compared to those at risk of sarcopenia. In a multivariable Cox regression analysis, normal muscle mass and an initial age at diagnosis of < 50 years emerged as significant prognostic markers. Longitudinally, survival was longest in patients with lack of TMT decline over the disease course.

Discussion: This analysis confirms TMT as an important prognostic marker in glioblastoma in two real-life cohorts. However, in order to establish TMT assessment as a routine marker for patient selection and therapeutic measures, further validation in prospective controlled trials is necessary.

Keywords: MGMT; CeTeG; glioblastoma; imaging; temporal muscle thickness.

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Conflict of interest statement

Lazaros Lazaridis received honoraria and travel support from Novocure. Michael Müther received honoraria and travel support from Medac. Teresa Schmidt received honoraria and travel support from Novocure. Christoph Oster received honoraria and travel support from Novocure. Almuth Friederike Kessler received travel support and research grants from Novocure. Clemens Seidel received honoraria for lectures, consultation, or advisory board participation from the following for‐profit companies: AbbVie, Bristol‐Myers Squibb, HRA Pharma, Medac, Novocure, Roche, and Seagen. Peter Hau received honoraria from Bayer, Medac, Novocure, and Seagen; travel support from Novocure and Medac. Ulrich Herrlinger received lecture and/or advisory board honoraria from Medac, Noxxon, AbbVie, Bayer, Janssen, and Karyopharm. Björn Scheffler is supported by the German Cancer Consortium (DKTK). Sied Kebir received honoraria and travel support from Novocure. Martin Glas reports honoraria from Roche, Novartis, UCB, AbbVie, Daiichi Sankyo, Novocure, Bayer, Janssen‐Cilag, Medac, Merck, Kyowa Kirin, travel support from Novocure and Medac, and a research grant from Novocure. All remaining authors have declared no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Examples of TMT assessment for patients from the CeTeG and Stupp cohorts. (A and B) indicate examples of patients at risk of sarcopenia (left) and patients with normal muscle mass (right) from the CeTeG (above) and Stupp cohort (below). TMT measurement was assessed on axial T1‐weighted contrast‐enhanced cranial MRI. The white lines indicate the exact calculation of TMT for both sides. MRI: Magnetic resonance imaging; TMT: Temporal muscle thickness.
FIGURE 2
FIGURE 2
Association of TMT with survival. (A and B) comparatively shows mPFS and mOS of the CeTeG and Stupp cohorts. In both cohorts, patients with sex‐specific TMT‐based normal muscle mass at baseline had significantly prolonged survival (C–F). (G) shows the results of a multivariable Cox regression analysis including all patients and featuring the canonical clinical factors with known prognostic relevance. (H) depicts the results of a multivariable Cox regression analysis including the CeTeG patients (left) and the Stupp patients (right). For both cohorts, mOS was longest in patients who did not experience a decline of TMT (relTMT ≥ 100%) in the course of the disease and shortest in patients who experienced a relevant decline in TMT (relTMT < 90%) in the disease course (I). mOS: Median overall survival; mPFS: Median progression‐free survival; TMT: Temporal muscle thickness.
FIGURE 3
FIGURE 3
Longitudinal analysis of TMT with survival. (A) shows the survival of patients from both cohorts subgrouped by first and third quartiles of relTMT values. (B) depicts the survival of patients from both cohorts stratified by increase versus decline of relTMT in the disease course. (C) illustrates the survival of patients from both cohorts subdivided by receiver operating characteristic (ROC) defined relTMT cutoff (Youden's index). In all subgroup analyses, higher relTMT values in the disease course were associated with statistically significant prolonged survival. TMT: Temporal muscle thickness.
See this image and copyright information in PMC

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