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"Franceschi, E"
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Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study
Background
Medulloblastoma is extremely rare in adults. The role of chemotherapy for average-risk adult patients remains controversial. Surgery and radiotherapy provide a significant disease control and a good prognosis, but about 25% of average-risk patients have a relapse and die because of disease progression. No data in average-risk adult patients are available to compareradiotherapy alone and radiotherapyfollowed byadjuvant chemotherapy.
Methods
We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016.
Results
Median age was 29 years (range 16–61). Based on histological subtypes, 15 patients (31.3%) had classic, 15 patients (31.3%) had desmoplastic, 5 patients (10.4%) had extensive nodularity and 2 patients (4.2%) had large cells/anaplastic medulloblastoma. Twenty-four patients (50%) received adjuvant radiotherapy alone and 24 (50%) received radiotherapy and chemotherapy. After a median follow-up of 12.5 years, we found that chemotherapyincreases progression-free survival (PFS-15 82.3 ± 8.0% in patients treated with radiotherapy and chemotherapyvs. 38.5% ± 13.0% in patients treated with radiotherapy alone
p
= 0.05) and overall survival (OS-15 89.3% ± 7.2% vs. 52.0% ± 13.1%,
p
= 0.02). Among patients receiving chemotherapy, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia (6 cases of G3 neutropenia [25%] and 3 cases of G4 neutropenia [13%]), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%).
Conclusions
Our study with a long follow up period suggests that adding adjuvant chemotherapy to radiotherapy might improve PFS and OS in average-risk adult medulloblastoma patients.
Journal Article
Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)
The efficacy of temozolomide strongly depends on O
6
-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m
2
/daily for 21 days every 28 days until disease progression. O
6
-methyl-guanine-DNA-methyl-tranferase (
MGMT
) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31–71) with a median KPS of 90 (range 60–100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18–51%). No correlation was found between the
MGMT
promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.
Journal Article
Euclid: The first statistical census of dusty and massive objects in the ERO/Perseus field
Our comprehension of the history of star formation at \\(z>3\\) relies on rest-frame UV observations, yet this selection misses the most dusty and massive sources, yielding an incomplete census at early times. Infrared facilities such as Spitzer and the James Webb Space Telescope have revealed a hidden population at \\(z=3\\)-\\(6\\) with extreme red colours, named HIEROs (HST-to-IRAC extremely red objects), identified by the criterion \\(H_E-ch2>2.25\\). Recently, Euclid Early Release Observations (ERO) have made it possible to further study such objects by comparing Euclid data with ancillary Spitzer/IRAC imaging. We investigate a \\(232\\) arcmin\\(^2\\) area in the Perseus field using VIS and NISP photometry, complemented by the four Spitzer channels and ground-based MegaCam bands (\\(u\\), \\(g\\), \\(r\\), \\( H\\), \\(i\\), \\(z\\)). Applying the colour cut yields \\(121\\) HIEROs; after removing globular clusters, brown dwarfs, and unreliable cases through visual inspection of multiband cutouts, we obtain a final sample of \\(42\\) robust HIEROs. Photometric redshifts and physical properties are estimated with the SED-fitting code Bagpipes. From the resulting \\(z_phot\\) and \\(M_*\\) values, we compute the galaxy stellar mass function at \\(3.5
Paper
Recent Advances in Diagnostic Approaches for Mucormycosis
Mucormycosis, an invasive fungal infection caused by members of the order Mucorales, often progresses fulminantly if not recognized in a timely manner. This comprehensive review discusses the latest developments in diagnostic approaches for mucormycosis, from traditional histopathology and culture-based methods to advanced and emerging techniques such as molecular assays, imaging, serology, and metabolomics. We discuss challenges in the diagnosis of mucormycosis and emphasize the importance of rapid and accurate identification of this life-threatening infection.
Journal Article
Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)
Background Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Methods Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m²) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m²) every 3 weeks for <=1 year. Results Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. Conclusions The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.
Journal Article
Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?
The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm
2
) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8–13), median survival was 18 years (95 % CI 9–28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0–97.2 %) and 60.2 % (95 % CI 36.9–83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).
Journal Article
Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)
To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mgday
−1
) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1–36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2–104+) weeks and PFS-6 was 14.3% (95% CI 4.0–32.7%). The median overall survival was 24.6 weeks (range 4–104+). No grade 3–4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.
Journal Article
Euclid: Estimation of the Impact of Correlated Readout Noise for Flux Measurements with the Euclid NISP Instrument
The Euclid satellite, to be launched by ESA in 2022, will be a major instrument for cosmology for the next decades. Euclid is composed of two instruments: the Visible instrument and the Near Infrared Spectrometer and Photometer (NISP). In this work, we estimate the implications of correlated readout noise in the NISP detectors for the final in-flight flux measurements. Considering the multiple accumulated readout mode, for which the UTR (Up The Ramp) exposure frames are averaged in groups, we derive an analytical expression for the noise covariance matrix between groups in the presence of correlated noise. We also characterize the correlated readout noise properties in the NISP engineering-grade detectors using long dark integrations. For this purpose, we assume a (1/f) α -like noise model and fit the model parameters to the data, obtaining typical values of \\(\\sigma ={19.7}_{-0.8}^{+1.1}\\) e − Hz−0.5, \\({f}_{\\mathrm{knee}}=({5.2}_{-1.3}^{+1.8})\\times {10}^{-3}\\,\\mathrm{Hz}\\) and \\(\\alpha ={1.24}_{-0.21}^{+0.26}\\). Furthermore, via realistic simulations and using a maximum likelihood flux estimator we derive the bias between the input flux and the recovered one. We find that using our analytical expression for the covariance matrix of the correlated readout noise we diminish this bias by up to a factor of four with respect to the white noise approximation for the covariance matrix. Finally, we conclude that the final bias on the in-flight NISP flux measurements should still be negligible even in the white readout noise approximation, which is taken as a baseline for the Euclid on-board processing to estimate the on-sky flux.
Journal Article
Temozolomide as salvage treatment in primary brain lymphomas
Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1–12) of temozolomide 150 mg m
−2
day
−1
, for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16–46%). One-year survival was 31% (95% confidence interval 16–46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.
Journal Article
Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas
Background
: Patients with recurrent or progressive low grade gliomas survive for a decade or more following diagnosis, and may be at a higher risk for treatment-related complications, such as cognitive impairment from radiotherapy.
Purpose
: The aim of the present study was to determine in patients with progressive or recurrent low grade gliomas, the response rate and toxicity incurred by a continued schedule of temozolomide chemotherapy administered before radiation therapy, and to explore correlations between response and survival with 1p/19q deletions and
MGMT
promoter methylation status.
Methods
: Progressive radio and chemotherapy naïve low grade glioma patients with O
6
-methyl-guanine-DNA-methyl-tranferase (
MGMT
) promoter status evaluation were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m
2
/daily for 21 days every 28 days for 12 cycles.
Results
: A total of 30 patients (median age 45 [range: 24.2–68.6] years) with a median KPS of 90 (range 60–90) were accrued. The overall response rate was 30% (9 partial responses); 17 patients (56.7%) had disease stabilization.
Conclusion
: The prolonged temozolomide schedule considered in the present study is followed by a high response rate; toxicity is acceptable. Further randomized trials should therefore be conducted to confirm the efficacy of this regimen as first-line therapy in patients with progressive low grade glioma.
Journal Article