Metronomic Temozolomide in Heavily Pretreated Patients With Recurrent Isocitrate Dehydrogenase Wild-type Glioblastoma: A Large Real-Life Mono-Institutional Study.

AIMS: Glioblastoma (GBM) is the most common primary malignant brain tumour in adults and frequently relapses. The aim of this study was to assess the efficacy and safety of metronomic temozolomide (TMZ) in the recurrent GBM population. MATERIALS AND METHODS: All patients treated at our centre between September 2013 and March 2021 were retrospectively reviewed. The main inclusion criteria were first-line therapy with the Stupp protocol, relapse after the first or subsequent line of therapy, treatment with a metronomic TMZ schedule (50 mg/m2 continuously) and histological diagnosis of isocitrate dehydrogenase wild-type GBM according to World Health Organization 2016 classification. RESULTS: In total, 120 patients were enrolled. The median follow-up was 15.6 months, the median age was 59 years, Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0-2 in 107 patients (89%). O6-methylguanine-DNA-methyltransferase (MGMT) was methylated in 66 of 105 (62%) evaluable patients. The median number of prior lines of treatment was 2 (range 1-7). Three (2%) patients showed a partial response; 48 (40%) had stable disease; 69 (57%) had progressive disease. The median overall survival from the start of metronomic TMZ was 5.4 months (95% confidence interval 4.3-6.4), whereas the median progression-free survival (PFS) was 2.6 months (95% confidence interval 2.3-2.8). At univariate analysis, MGMT methylated and unmethylated patients had a median PFS of 2.9 and 2.1 months (P = 0.001) and a median overall survival of 5.6 and 4.4 months (P = 0.03), respectively. At multivariate analysis, the absence of MGMT methylation (hazard ratio = 2.3, 95% confidence interval 1.3-3.9, P = 0.004) and ECOG-PS ≤ 2 (hazard ratio = 0.5, 95% confidence interval 0.3-0.9, P = 0.017) remained significantly associated with PFS, whereas ECOG-PS ≤ 2 (hazard ratio = 0.4, 95% confidence interval 0.3-07, P = 0.001) was the only factor associated with overall survival. The most common grade 3-4 toxicities were haematological (lymphopenia 10%, thrombocytopenia 3%). CONCLUSIONS: Rechallenge with metronomic TMZ is a well-tolerated option for recurrent GBM, even in pretreated patients. Patients with methylated MGMT disease and good ECOG-PS seem to benefit the most from this treatment.

T2-weighted, apparent diffusion coefficient and 18F-FDG PET histogram analysis of rectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The aim of our study was to investigate the correlation among T2-weighted (T2w) images, apparent diffusion coefficient (ADC) maps, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images, histogram analysis and the pathological response in locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (pCRT). METHODS: Patients with LARC were prospectively enrolled between February 2015 and August 2018 and underwent PET/magnetic resonance imaging (MRI). MRI included T2w and diffusion-weighted imaging (DWI)-sequences. ADC maps and PET images were matched to the T2w images. Voxel-based standardized uptake values (SUVs,) ADC and T2w-signal-intensity values were collected from the volumes of interest (VOIs) and mean, skewness and kurtosis were calculated. Spearman's correlation coefficient was applied to evaluate the correlation among the variables and tumor regression grade (TRG), T stage, N stage and fibrosis. RESULTS: Twenty-two patients with biopsy-proven LARC in the low or mid rectum were enrolled [17 males, mean age was 69 years (range 49-85 years)]. Seven patients experienced complete regression (TRG1). A significant positive correlation was found between SUV mean values (ρ = 0.480; p = 0.037) and TRG. No other significant correlations were found. CONCLUSIONS: Histogram analysis of SUV values is a predictor of TRG in LARC.