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Bellu et al. J Cancer Metastasis Treat 2021;7:29  https://dx.doi.org/10.20517/2394-4722.2021.89  Page 3 of 8

               an expert neuroradiologist, according to the Response Assessment in Neuro-Oncology (RANO) criteria for
                                     [3]
               diffuse low-grade gliomas ; patient outcomes were described in terms of progression free survival (PFS)
               and overall survival (OS).

               As regards statistical analysis, PSF was defined as the time between diagnosis and clinical or radiological
               progression or death, and OS was defined as the time between diagnosis and patient death; both PFS and OS
               were calculated using Kaplan-Meier survival curves. Univariate analyses were performed for the Eastern
               Cooperative Oncology Group (ECOG) performance status (PS), MGMT promoter methylation, IDH1
               mutation, type of first-line treatment [RT + temozolomide (TMZ), RT alone, or TMZ alone], histological
               subtype (astrocytoma vs. oligodendroglioma), best response to treatment [stable disease (SD), partial
               response (PR), complete response (CR), or progressive disease], and second-line treatment (yes vs. no).


               RESULTS
               After reviewing patient records, 33 patients were eligible for the study. Patient features and tumor
               characteristics are summarized in Table 1.


               Patients included 22 males (67%) and 11 females (33%). ECOG PS was 0-1 in 21 patients (64%) and ≥ 2 in 12
               patients (36%). Biopsy was performed in 22 cases (67%); at the histological analysis, 16 (73%) were
               astrocytomas and 6 (27%) were oligodendrogliomas. MGMT promoter methylation was detected in 14
               patients (42%), and it was methylated in eight (57%). The IDH1 mutation status was studied in 16 out of 22
               cases (73%), and it had mutated in 10 patients (63%). With regard to the type of treatment, 9 patients (27%)
               underwent concomitant RT plus TMZ, 22 patients (67%) only received TMZ, and 2 patients (6%) received
               RT alone; the choice of treatment was at the physician’s discretion, essentially based on ECOG PS and
               extent of disease. We then analyzed the best radiological response on the MRI, finding a complete response
               in 1 case (3%), partial response in 9 patients (27%) and stable disease in 15 patients (45%). Only eight
               patients (25%) had a progressive disease (Figure 1 shows a partial response in the case of diffuse
               astrocytoma).

               Finally, with regard to patient outcome, we found a PFS of 19.1 months and an OS of 30.7 months among
               all patients [Figure 2]; according to the ECOG PS, PFS was 34.6 months vs. 3.4 months for PS 0-1 and ≥ 2 (P
               < 0.0001), and OS was 42 months vs. 8.9 months (P < 0.0001), respectively [Table 2].


               With reference to the histological subtype, PFS between astrocytic and oligodendroglial tumors was 41.6
               months vs. 28.6 months (P = 0.7), while OS was 42.0 months vs. 52.7 months (P = 0.8), respectively.

               The presence of MGMT methylation was associated with longer PFS (41.6 months vs. 8.9 months, P = 0.05)
               and OS (52.7 months vs. 14.6 months, P = 0.009), while, in regard to IDH1 mutation, PFS was 52.7 months
               vs. 8.9 months (P = 0.006) and OS was 52.7 months vs. 41 months (P = 0.02).

               It is worth noting that no significant difference was found in relation to the different types of treatment: for
               the concomitant scheme (RT + TMZ) vs. RT or TMZ alone, PFS was 11.1 months vs. 19.1 months (P = 0.2)
               and OS was 14.7 months vs. 30.7 months (P = 0.7), respectively.

               Moreover, radiological response was correlated with survival; indeed, patients with partial or complete
               response had a longer OS than those with stable or progressive disease (38.5 months in CR/PR vs. 4.0
               months in PD, P < 0.0001).
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