Background/Aim: To report the feasibility and oncological outcomes in breast cancer patients treated with a short hypofractionated radiotherapy schedule. Patients and Methods: We evaluated 380 breast ...cancer patients treated with ten daily fractions of radiotherapy up to 39 Gy on tumor bed. Primary endpoint was local relapse rate (LRR). Secondary endpoints were overall survival (OS) and metastasis-free survival (MFS). Results: The median follow up was 5.0 years. Two- and 5-year LRR rates were 0.2 and 2%, respectively. Two- and 5-year MFS rates were 96.1% and 90.5%, respectively. Two and 5-year OS rates were 97.4% and 95%, respectively. Conclusion: This short schedule may represent an alternative option to standard mild hypofractionated radiotherapy in breast cancer patients due to its excellent feasibility and very low recurrence rate.
•LGN volume is significantly reduced after ON in a cohort of early RRMS patients.•ON may contribute to drive LGN atrophy through anterograde TSD.•Anterograde TSD does not involve primary visual ...cortex in early disease phases.•Inflammatory and neurodegenerative processes coexist since MS onset.
Optic pathway is considered an ideal model to study the interaction between inflammation and neurodegeneration in multiple sclerosis (MS).
Optical Coherence Tomography (OCT) and 3.0 T magnetic resonance imaging (MRI) were acquired in 92 relapsing remitting (RR) MS at clinical onset. Peripapillary RNFL (pRNFL) and macular layers were measured. White matter (WM) and gray matter (GM) lesion volumes (LV), lateral geniculate nucleus (LGN) volume, optic radiations (OR) WM LV, thickness of pericalcarine cortex were evaluated. OCT and MRI control groups (healthy controls HC-OCT and HC-MRI) were included.
A significant thinning of temporal pRNFL and papillo-macular bundle (PMB) was observed (p<0.001) in 16 (17%) patients presented with monocular optic neuritis (MSON+), compared to 76 MSON- and 30 HC (-15 μm). In MSON-, PMB was reduced (-3 μm) compared to HC OCT (p<0.05). INL total volume was increased both in MSON+ (p<0.001) and MSON- (p = 0.033). Inner retinal layers volumes (macular RNFL, GCL and IPL) were significantly decreased in MSON+ compared to HC (p<0.001) and MSON- (p<0.001). Reduced GCL volume in the parafoveal ring was observed in MSON- compared to HCOCT (p < 0.05). LGN volume was significantly reduced only in MSON+ patients compared to HC-MRI (p<0.001) and MSON- (p<0.007). GCL, IPL and GCIP volumes associated with ipsilateral LGN volume in MSON+ and MSON-. Finally, LGN volume associated with visual cortex thickness with no significant difference between MSON+ and MSON-.
Anterograde trans-synaptic degeneration is early detectable in RRMS presenting with optic neuritis but does not involve LGN.
Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in ...overall survival (OS) in adjuvant breast cancer trials.
Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer–free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall’s τ and R2 ≥ 0.70 were considered as indicators of a clinically relevant surrogacy.
Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49–65). After a median follow-up of 10.3 years (IQR 6.4–14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall’s τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI.
Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials.
This analysis was supported by the Italian Association for Cancer Research (“Associazione Italiana per la Ricerca sul Cancro”, AIRC; IG 2017/20760) and by Italian Ministry of Health–5 × 1000 funds (years 2021–2022).
The MuSC-19 study: The Egyptian cohort Zakaria, Magd; Ponzano, Marta; Schiavetti, Irene ...
Multiple sclerosis and related disorders,
11/2021, Letnik:
56
Journal Article
Odprti dostop
This study aimed to report the severity of COVID-19 in a cohort of Egyptian patients with multiple sclerosis (MS) with particular attention on the impact of disease modifying drugs (DMDs).
We ...included 119 MS patients recruited from two centers, Ain-Shams university and Cairo university with confirmed or suspected COVID-19 during the period from May to September 2020 as a part of the MuSC-19 project. Univariate logistic regression was fitted to assess risk factors for severe COVID-19 (at least one outcome among hospitalization, ICU admission and death).
Females were 77%, mean age was 34 years, mean duration of MS was 5.28 years, median EDSS was 3, most of the patients (83%) had RRMS, while 15% and 2% had respectively SPMS and PPMS. Only eleven patients (9% of study population) had a severe outcome and 3 patients (3%) died. Headache was the only symptom significantly associated with the severity of COVID-19 (OR=10.85, P = 0.001). There was no association between any of the DMDs and severe COVID-19 outcome.
This study showed an acceptable safety profile of DMDs in Egyptian MS patients who developed COVID-19, as 91% of the cohort had a favorable outcome. Headache as a symptom associated with severe outcome in Egyptian patients' needs further validation.
Many studies investigated the association between air pollution and Covid-19 severity but the only study focusing on patients with Multiple Sclerosis (MS) exclusively evaluated exposure to PM2.5. We ...aim to study, in a sample of MS patients, the impact of long-term exposure to PM2.5, PM10 and NO2 on Covid-19 severity, described as occurrence of pneumonia.
A 1:2 ratio case-control study was designed, differentiating cases and controls based on Covid-19 pneumonia. Associations between pollutants and outcome were studied using logistic regression. Weighted quantile sum (WQS) logistic regression was used to identify the individual contribution of each pollutant within the mixture; Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression was performed to confirm the variable selection from WQS. All the analyses were adjusted for confounders selected a priori.
Of the 615 eligible patients, 491 patients provided detailed place of exposure and were included in the principal analysis. Higher concentrations of air pollutants were associated with increased odds of developing Covid-19 pneumonia (PM2.5: 3rd vs 1st tercile OR(95% CI)=2.26(1.29;3.96); PM10: 3rd vs 1st tercile OR(95% CI)=2.12(1.22;3.68); NO2: 3rd vs 1st tercile OR(95% CI)=2.12(1.21;3.69)). Pollutants were highly correlated with each other; WQS index was associated to an increased risk of pneumonia (β=0.44; p-value=0.004) and the main contributors to this association were NO2 (41%) and PM2.5 (34%). Consistently, Lasso method selected PM2.5 and NO2.
Higher long-term exposure to PM2.5, PM10 and NO2 increased the odds of Covid-19 pneumonia among MS patients and the most dangerous pollutants were NO2 and PM2.5.
The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main ...aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort.
Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab.
We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076).
Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.
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