Maximum 11C-methionine PET uptake as a prognostic imaging biomarker for newly diagnosed and untreated astrocytic glioma

This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II–IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10–0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23–22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27–58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09–0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08–0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81–109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II–IV astrocytic glioma.

MPC-2 Clinical course and prognosis of lower-grade glioma, IDH wildtype and pTERT mutant

Background and Purpose: In the cIMPACT-Now update 3, it was proposed that grade 2 astrocytic gliomas without IDH-mutations and grade 3 astrocytic gliomas with TERT promoter mutations should be designated as diffuse IDH wildtype astrocytic glioma with molecular features of WHO grade IV glioblastoma. Therefore, we investigated whether this group of tumors actually corresponds to grade IV prognostically in cases that we encountered ourselves. Cases and Methods: Among the 65 patients having primary astrocytic glioma who were operated in our hospital from January 2016 to March 2021, the prognostic values of seven patients with lower-grade glioma, IDH wildtype, and pTERT mutant were investigated. Results: Among the seven patients, the median age was 59 years (50–66 years). Four of them had anaplastic astrocytoma, two had diffuse astrocytoma, and no tumor lesion could be identified upon histological examination for one patient. The male-to-female ratio was 1:6. MGMT methylation was observed in two patients (29%). The median survival was 20 months, with a significantly worse prognosis when compared with lower-grade glioma without the TERT promoter mutation (13 patients: median survival 40 months), but a better prognosis when compared with glioblastoma (45 patients: median survival 13 months) (Log-rank p = 0.0051). Conclusion: Although EGFR amplification, combined whole chromosome 7 gain, and whole chromosome 10 loss were not examined, the prognostic value of lower-grade glioma, IDH wildtype, and pTERT mutant was not as poor as that of glioblastoma. Further investigation is required to confirm whether these groups of tumors should be treated in the same way as grade IV glioblastoma.

PATH-25. H3 K27M-MUTANT DIFFUSE NON-MIDLINE GLIOMA: REPORT OF A CASE WITH EXTENDED FOLLOW-UP

H3 K27M-mutant diffuse gliomas without midline involvement are extremely rare and their clinical behavior remains elusive due to limited reported follow-up data. We describe an H3 K27M-mutant diffuse non-midline glioma patient with extended follow-up. A 34-year-old woman presented with headache, memory loss, periods of changes in taste and smell, and confusion. Imaging studies revealed an 2.3 cm expansile T2/flair hyperintensity with patchy postcontrast enhancement centered in the left amygdala without associated restricted diffusion and no involvement of the midline structures. The tumor was debulked and consisted of a mitotically active infiltrating astrocytic glioma without tumor necrosis or microvascular proliferation, consistent with anaplastic astrocytoma. Targeted 187-gene neuro-oncology NGS testing detected an H3F3A K27M mutation along with a PTPN11 and a PPM1D mutation. FISH 1p/19q-codeletion testing was negative. MGMT promoter was unmethylated. The patient was treated with chemoradiation with temozolomide for 6 weeks followed by 12 cycles of temozolomide. Four years after initial resection, an area of increased post-contrast enhancement indicating tumor recurrence/progression was noted. Partial resection of the recurrent tumor revealed a mitotically active infiltrating astrocytic glioma with tumor necrosis consistent with glioblastoma. Molecular profiling of the recurrent tumor by the neuro-oncology NGS panel detected similar mutational profile (identical H3F3A K27M and PTPN11 mutation; different PPM1D mutation) with an additional SOS1 mutation. The patient completed 4 cycles of Lomustine and although clinically stable, imaging studies showed slight increase in residual tumor size concerning for tumor progression. Lomustine was discontinued, Bevacizumab therapy was initiated and patient was enrolled in clinical trial (NCT02525692). Despite tumor progression, this patient has had a relatively long disease course (5 years) suggesting that H3 K27M-mutant non-midline diffuse gliomas although molecularly similar, may follow a more favorable clinical course than their midline counterparts possibly due to the hemispheric location, which is more amenable for surgical resection.

Maximum Lesion-To-Contralateral Normal Brain Tissue Ratio of 11C-Methionine PET as a Prognostic Imaging Biomarker for Newly Diagnosed and Untreated Astrocytic Glioma

Purpose: This study aimed whether the uptake of amino tracer positron emissiontomography (PET) can be used as an additional imaging biomarker to estimatethe prognosis of glioma.Methods: Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) gradeⅡ-Ⅳ astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution.Results: Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (PFS) (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p<0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95%CI 1.23-22.8, p=0.025; glioblastoma: HR 11.52, 95%CI 2.27-58.47, p=0.0032), preoperative KPS≥80 (HR 0.23, 95%CI 0.09-0.62, p=0.004), maximum lesion-to-contralateral normal brain tissue (LN max)≥4.03 (HR 0.24, 95%CI 0.08-0.71, p=0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95%CI 1.81-109.2, p=0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max≥ 4.03 (29.3 months) than in patients with LN max<4.03 (not reached; p=0.03). OS differed significantly between patients with IDH mutant/LN max<4.03 and patients with IDH mutant/LN max ≥4.03.Conclusions: LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO gradeⅡ-Ⅳ astrocytic glioma.

Maximum Lesion-to-contralateral Normal Brain Tissue Ration of 11C-methionine PET as a Prognostic Imaging Biomarker for Newly Diagnosed and Untreated Astrocytic Glioma

Purpose: This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma.Methods: Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) gradeⅡ-Ⅳ astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution.Results: Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (PFS) (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p<0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95%CI 1.23-22.8, p=0.025; glioblastoma: HR 11.52, 95%CI 2.27-58.47, p=0.0032), preoperative KPS≥80 (HR 0.23, 95%CI 0.09-0.62, p=0.004), maximum lesion-to-contralateral normal brain tissue (LN max)≥4.03 (HR 0.24, 95%CI 0.08-0.71, p=0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95%CI 1.81-109.2, p=0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max≥ 4.03 (29.3 months) than in patients with LN max<4.03 (not reached; p=0.03). OS differed significantly between patients with IDH mutant/LN max<4.03 and patients with IDH mutant/LN max ≥4.03.Conclusions: LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO gradeⅡ-Ⅳ astrocytic glioma.

Association of Angiogenic Cells in the Tumour Microenvironment and the Circulating Matured Endothelial Cells in Astrocytic Glioma

Introduction: Astrocytic gliomas are the most common and lethal intracranial brain tumours and rely on angiogenesis for the tumour development. Endothelial progenitor cells (EPCs) contribute to the angiogenesis of glioma tumour. Objectives: The study aimed to investigate the matured circulating endothelial cells population in the peripheral blood mononuclear cells (PBMCs) and its associations with tissue resident angiogenic cells in astrocytic glioma patients. Methods: A total of 22 astrocytic glioma patients were recruited from Hospital Universiti Sains Malaysia. Tumour were sliced and stained with CD133+ and VEGFA+ for angiogenic cells (n=22). The circulating (CD133-/VEGFR2+) matured endothelial cells in PBMCs (n=22) were quantified using FACS. The paired t-test and Pearson correlation test were used for the data analysis. Results: The angiogenic cells in brain tumour tissue were significantly higher compared to adjacent normal brain tissue (median 1.07±0.96% vs. median 0.69±0.68%; Wilcoxon signed rank test Z=-3.100; p=0.002). Positive correlation was found between the angiogenic cells of brain tumour tissue and adjacent normal brain tissue (Spearman’s rho correlation test, r=0.56; p=0.007). Significant positive correlation was found between matured endothelial cells in peripheral circulating systems and angiogenic cells in tumour of astrocytic glioma patients (Pearson correlation test, r=0.60, p=0.003).Conclusion:The findings of the study give support to the possible roles of EPCs in astrocytic glioma patients. Thus targeting tissue resident angiogenic cells and matured circulating endothelial cells by antiangiogenic treatment might be useful to prevent the tumour growth.

PATH-27. CLINICAL, RADIOLOGIC AND PROGNOSTIC PROFILE OF IDH WILD TYPE DIFFUSE ASTROCYTOMA WITH MOLECULAR FEATURES OF GLIOBLASTOMA

BACKGROUND cIMPACT-NOW-3 recommends that IDH-wildtype diffuse astrocytic glioma Grade II or III with EGFR amplification, or combined whole chromosome 7 gain and whole chromosome 10 loss, or TERT promoter mutation should receive an integrated classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The aims of this study were: Outline the features of a cohort of patients with molecular glioblastoma according to the above criteria; Assess clinical and molecular factors that may inform prognosis; Determine if cIMPACT-NOW-3 recommendation changed clinical practice and clinical trial enrolment. METHODS 61 patients diagnosed with IDH-wildtype diffuse astrocytic glioma Grade II or III and EGFR amp or mTERT or chromosome (+7/-10) between 2011 and 2019 at MGH were included in this single center retrospective cohort study. Data collected: sex, age, extent of surgery, functional status, histological grade, molecular diagnostics and treatment. Progression was defined using RANO criteria, progression was quantified in terms of months from the initial surgery. Survival was defined in terms of months from initial surgery to date of death or last known visit. RESULTS mOS was 16 months, mPFS was 9 months. 14 patients (23%) survived &gt; 24 months, 7 ≥ 36 months (mOS 32 months; 9 deceased). The probability of survival in patients with markedly enhancing tumors was 0.5 at 3 months versus 0.5 at 11 months in non-enhancing tumors. The probability of survival in patients who underwent biopsy only was 0.5 at 5 months compared to 0.5 at 12 months in patients with maximally resected tumors. 1 patient was enrolled in a clinical trial at diagnosis. 6 were enrolled at time of recurrence. CONCLUSIONS mOS and pFS in the deceased patients was comparable to historical data on survival in IDH wild-type glioblastomas. Inclusion criteria in clinical trials have not reflected the cIMPACT-NOW-3 recommendation so far.