Research ArticleClinical Investigation
Open Access

Prognostic Value of TSPO PET Before Radiotherapy in Newly Diagnosed IDH–Wild-Type Glioblastoma

Nathalie L. Albert, Debie V. Nelwan, Daniel F. Fleischmann, Stefanie Quach, Katharina von Rohr, Lena Kaiser, Nico Teske, Lena M. Unterrainer, Laura M. Bartos, Viktoria C. Ruf, Matthias Brendel, Markus J. Riemenschneider, Christian Wetzel, Jochen Herms, Rainer Rupprecht, Niklas Thon, Joerg-Christian Tonn, Claus Belka, Peter Bartenstein, Louisa von Baumgarten, Maximilian Niyazi, Marcus Unterrainer and Adrien Holzgreve
Journal of Nuclear Medicine August 2023, jnumed.122.265247; DOI: https://doi.org/10.2967/jnumed.122.265247

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Kaplan–Meier curves of OS for entire patient group using median split of SUVmax (A), age (B), MGMT promoter methylation status (C), and median split of tumor volume on T2-weighted MRI (T2 vol.) (D). ⊕ = methylated; ⊖ = unmethylated.

  • FIGURE 2.
    FIGURE 2.

    (A) 76-y-old male patient with left precentral IDH–wild-type glioblastoma (MGMT promoter-methylated, telomerase reverse transcriptase promoter C228T mutation; TSPO HAB) before hypofractionated radiotherapy and temozolomide chemotherapy. Tumoral TSPO radioligand uptake was high (SUVmax, 2.4), and survival was short (OS, 4.5 mo). (B) 71-y-old female patient with left postcentral–parietal IDH–wild-type glioblastoma (MGMT promoter-methylated, telomerase reverse transcriptase promoter C250T mutation; TSPO MAB) before hypofractionated radiotherapy and temozolomide chemotherapy. Tumoral TSPO radioligand uptake was low (SUVmax, 1.8), and survival was long (OS, 25.8 mo). CE-T1w = contrast-enhanced T1-weighted.

Tables

  • TABLE 1.

    Patient Characteristics

    CharacteristicData
    Age (y)63.3 (30.6–84.2)
    Sex
     Male27 (60.0%)
     Female18 (40.0%)
    MGMT promoter methylation status
     Methylated12 (26.7%)
     Unmethylated33 (73.3%)
    TERT promoter mutation status
     Mutant39 (86.7%)
      C250T mutation15 (53.3%)
      C228T mutation24 (33.3%)
     Wild-type6 (13.3%)
    KPS80% (60–100%)
    Mode of radiotherapy
     Conventional23 (51.1%)
     Hypofractionated22 (48.9%)
    Mode of surgery
     Stereotactic biopsy35 (77.8%)
     Microsurgical resection10 (22.2%)
    Contrast enhancement
     Yes40 (88.9%)
     No5 (11.1%)
    CE-T1w MRI volume (mL)11.1 (0.0–112.6)
    T2w MRI volume (mL)40.9 (0.0–272.0)
    TSPO polymorphism genotype
     LAB6 (13.3%)
     MAB15 (33.3%)
     HAB18 (40.0%)
     Not specified6 (13.3%)
    SUVmax2.2 (1.0–4.7)

    • MGMT = O6-alkylguanine DNA methyltransferase gene; TERT = telomerase reverse transcriptase gene; KPS = Karnofsky performance status scale; CE-T1w = contrast-enhanced T1-weighted; T2w = T2-weighted.

    • Qualitative data are number and percentage; continuous data are median and range.

  • TABLE 2.

    Univariate Survival Analyses

    OSPFS
    ParameterMedian OSSignificance*Median PFSSignificance*
    AgeP = 0.046P = 0.014
     Median < 63 y, n = 2216.33 (9.39–23.27)10.41 (7.07–13.76)
     Median ≥ 63 y, n = 239.69 (7.28–12.11)5.88 (3.46–8.30)
    SexP = 0.330P = 0.259
     Male, n = 2710.48 (2.90–18.06)6.41 (3.12–9.70)
     Female, n = 1810.84 (8.32–13.37)9.69 (5.94–13.45)
    MGMT promoter methylation statusP = 0.032P = 0.028
     Methylated, n = 1219.38 (3.16–35.61)10.84 (4.60–17.09)
     Unmethylated, n = 3310.42 (8.60–12.23)7.26 (4.49–10.03)
    TERT promoter mutation statusP = 0.939P = 0.896
     Mutant, n = 3910.42 (8.04–12.79)7.69 (4.99–10.38)
     Wild-type, n = 611.30 (6.93–15.70)8.35 (3.02–13.67)
    KPSP = 0.117P = 0.104
     Median < 80, n = 268.61 (4.83–12.38)6.21 (4.32–8.10)
     Median ≥ 80, n = 1917.77 (13.15–22.40)9.69 (7.54–11.84)
    Mode of radiotherapyP = 0.105P = 0.175
     Conventional, n = 2316.33 (11.48–21.18)8.90 (7.41–10.40)
     Hypofractionated, n = 226.83 (0.72–12.95)5.29 (2.61–7.97)
    Conventional radiochemotherapyP = 0.081P = 0.024
     ≥ 1 cycle adjuvant temozolomide, n = 1219.29 (13.99–24.58)10.42 (8.93–11.90)
     No adjuvant temozolomide, n = 119.86 (3.67–16.04)6.21 (5.50–6.92)
    Hypofractionated radiotherapyP = 0.064P = 0.100
     With concomitant temozolomide, n = 1310.84 (0.0–26.94)8.08 (1.21–14.96)
     Without concomitant temozolomide, n = 96.83 (1.16–12.51)5.29 (3.98–6.60)
    Mode of surgeryP = 0.118P = 0.443
     Stereotactic biopsy, n = 359.86 (7.31–12.41)6.83 (3.90–9.77)
     Microsurgical resection, n = 1019.29 (16.77–21.80)8.35 (2.61–7.97)
    Contrast enhancementP = 0.070P = 0.419
     Yes, n = 409.86 (8.63–11.08)6.83 (4.54–9.13)
     No, n = 521.22 (17.42–25.03)10.61 (7.79–13.43)
    CE-T1w MRI volumeP = 0.289P = 0.372
     Median < 11.1 mL, n = 2315.77 (7.90–23.64)8.90 (7.52–10.29)
     Median ≥ 11.1 mL, n = 226.21 (0.70–11.72)5.65 (3.65–7.65)
    T2w MRI volumeP = 0.031P = 0.118
     Median < 40.9 mL, n = 2317.77 (6.20–29.34)8.90 (6.47–11.33)
     Median ≥ 40.9 mL, n = 226.83 (1.32–12.35)5.65 (2.90–8.41)
    TSPO polymorphism genotypeP = 0.360P = 0.333
     LAB10.84 (8.91–12.77)9.69 (5.91–13.48)
     MAB17.77 (7.99–27.56)8.90 (4.76–13.05)
     HAB8.28 (0.78–15.79)5.29 (3.72–6.86)
    SUVmaxP = 0.037P = 0.333
     Median < 2.2, n = 2317.77 (4.40–31.14)8.41 (7.56–9.23)
     Median ≥ 2.2, n = 228.28 (3.67–12.89)6.83 (3.63–10.04)

    • ↵* Bold font highlights the statistically significant associations.

    • MGMT = O6-alkylguanine DNA methyltransferase gene; TERT = telomerase reverse transcriptase gene; KPS = Karnofsky performance status scale; CE-T1w = contrast-enhanced T1-weighted; T2w = T2-weighted.

    • Data in parentheses are 95% CI.

  • TABLE 3.

    Comparison of Patients with Low Versus High Tumoral Uptake on TSPO PET

    CharacteristicSUVmax < 2.2, n = 23SUVmax ≥ 2.2, n = 22Significance*
    Age (y)62.6 (51.2–80.4)63.9 (30.6–84.2)P = 0.910
    SexP = 0.270
     Male12 (52.2%)15 (68.2%)
     Female11 (47.8%)7 (31.8%)
    MGMT promoter methylation statusP = 0.563
     Methylated7 (30.4%)5 (22.7%)
     Unmethylated16 (69.6%)17 (77.3%)
    TERT promoter mutation statusP = 0.954
     Mutant20 (86.9%)19 (86.4%)
     C250T mutation9 (39.1%)6 (27.3%)
     C228T mutation11 (47.8%)13 (59.1%)
     Wild-type3 (13.0%)3 (13.6%)
    KPS80% (60–100%)80% (60–90%)P = 0.161
    Mode of surgeryP = 0.528
     Stereotactic biopsy17 (73.9%)18 (81.8%)
     Microsurgical resection6 (26.1%)4 (18.2%)
    Mode of radiotherapyP = 0.185
     Conventional14 (60.9%)9 (40.9%)
     Hypofractionated9 (39.1%)13 (59.1%)
    Concomitant temozolomideP = 0.266
     Yes19 (82.6%)15 (68.2%)
     No4 (17.4%)7 (31.8%)
    Contrast enhancementP = 0.022
     Yes18 (78.3%)22 (100.0%)
     No5 (21.7%)0 (0.0%)
    CE-T1w MRI volume (mL)10.2 (0.0–112.6)14.5 (0.4–78.6)P = 0.188
    T2w MRI volume (mL)35.2 (0.0–272.0)56.2 (0.4–168.5)P = 0.188

    • ↵* Bold font highlights the statistically significant associations.

    • MGMT = O6-alkylguanine DNA methyltransferase gene; TERT = telomerase reverse transcriptase gene; KPS = Karnofsky performance status scale; CE-T1w = contrast-enhanced T1-weighted; T2w = T2-weighted.

    • Qualitative data are number and percentage; continuous data are median and range.

  • TABLE 4.

    Multivariate Survival Analyses

    OSPFS
    ParameterHazard ratioSignificance*Hazard ratioSignificance*
    Age2.573 (1.284–5.156)P = 0.0082.604 (1.341–5.057)P = 0.005
    MGMT promoter methylation status3.174 (1.368–7.363)P = 0.0072.695 (1.266–5.737)P = 0.010
    T2w MRI volume1.896 (0.993–3.619)P = 0.053——
    SUVmax2.212 (1.115–4.386)P = 0.023——

    • ↵* Bold font highlights the statistically significant associations.

    • T2w = T2-weighted.

    • Data in parentheses are 95% CI.

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