Publications by authors named "Luisa Bellu"

19 Publications

  • Page 1 of 1

Influence of different lipid emulsions on specific immune cell functions in head and neck cancer patients receiving supplemental parenteral nutrition: An exploratory analysis.

Nutrition 2021 Jan 30;86:111178. Epub 2021 Jan 30.

Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. Electronic address:

Objectives: The effect of diet on immune responses is an area of intense investigation. Dietary lipids have been shown to differently influence and fine-tune the reactivity of immune cell subsets, thus potentially affecting clinical outcomes. Patients with head and neck squamous cell carcinoma face malnutrition, due to swallowing impairment related to the tumor site or to treatment sequalae, and may need supplemental parenteral nutrition (SPN) in addition to oral feeding when enteral nutrition is not feasible. Additionally, immune depression is a well-known complication in these patients. Parenteral nutrition (PN) bags contain amino acids, minerals, electrolytes and mostly lipids that provide calories in a concentrated form and are enriched with essential fatty acids. The aim of this study was to investigate multiple parameters of the immune responses in a cohort of patients with head and neck squamous cell carcinoma undergoing supplemental PN with bags enriched in ω-3 or ω-9 and ω-6 fatty acids.

Methods: To our knowledge, this was the first exploratory study to investigate the effects of two different PN lipid emulsions on specific immune cells function of patients with advanced head and neck squamous carcinoma. ω-3-enriched fish-oil-based- and ω-6- and ω-9-enriched olive-oil-basedSPN was administered to two groups of patients for 1 wk in the context of an observational multicentric study. Polychromatic flow cytometry was used to investigate multiple subsets of leukocytes, with a special focus on cellular populations endowed with antitumor activity.

Results: Patients treated with olive-oil-based PN showed an increase in the function of the innate (natural killer cells and monocytes) and adaptive (both CD4 and CD8 cells) arms of the immune response.

Conclusion: An increase in the function of the innate and adaptive arms of the immune response may favor antitumoral responses.
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http://dx.doi.org/10.1016/j.nut.2021.111178DOI Listing
January 2021

Treatment of patients with glioma during the COVID-19 pandemic: what we learned and what we take home for the future.

Neurosurg Focus 2020 12;49(6):E10

2Radiotherapy and Radiosurgery.

Objective: Coronavirus disease 2019 (COVID-19) has changed the way in which cancer is treated. Patients with high-grade glioma (HGG) are believed to be in a vulnerable category. The aim of this study was to describe the experience of a hub cancer center and the measures that were put in place for treatment of patients with newly diagnosed and recurrent glioma.

Methods: To prevent in-hospital contagion and preserve the safety of health professionals and patients, specific protocols and strict regulations were introduced. Physical distancing, use of surgical masks, and diligent hand hygiene were adopted. Each case was discussed in a multidisciplinary board meeting before treatment. All patient candidates for surgical procedures were tested for SARS-CoV-2 with a nasopharyngeal swab and a chest CT scan. Indications for surgery were the radiological suspicion of HGG in patients with a good performance status and/or the rapid and progressive occurrence of neurological deficits. Adjuvant treatments were performed only in cases of HGG. This therapy consisted of conventional fractional radiotherapy (RT; 60 Gy/30 fractions) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT) in younger patients; in elderly patients, a short course of RT was employed (40.5 Gy/15 fractions). For recurrent HGG, treatments were assessed after a careful evaluation of the patient's general condition, neurological status, and risk of early impairment in neurological status if not treated. During simulation CT for the RT plan, each patient underwent a chest CT study. In cases in which an imaging study was suspicious for COVID-19 pneumonia, the patient was immediately isolated and rapidly underwent nasopharyngeal swab testing.

Results: Between March 1 and April 30, 2020, 23 HGGs were treated, and these cases are included in the present evaluation. Fifteen patients harboring newly diagnosed glioblastoma (GBM) underwent resection followed by a regimen of chemotherapy and RT, and 3 patients with newly diagnosed anaplastic oligodendroglioma underwent surgery followed by adjuvant RT. Five patients were treated for recurrent GBM, and they received surgery plus adjuvant RT. One patient in whom the simulation CT study was suspicious for COVID pneumonia was tested with a nasopharyngeal swab, which proved positive for SARS-CoV-2 infection. No patients contracted COVID-19 during hospitalization for surgery or during RT treatment. Corticosteroid therapy was administered to all patients beginning on the 1st day of RT.

Conclusions: The authors' experience during the COVID-19 pandemic showed that patients with HGG can be treated in the most effective manner without a compromise in safety. Careful selection criteria and a multidisciplinary evaluation are pivotal to assessing the optimal therapeutic strategy.
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http://dx.doi.org/10.3171/2020.9.FOCUS20704DOI Listing
December 2020

The 70-year-old newly diagnosed glioblastoma patients are older than the 65-year-old? Outcome evaluation of the two categories in a matched case control study with propensity score balancing.

Radiother Oncol 2021 Mar 25;156:49-55. Epub 2020 Nov 25.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center-IRCCS, Rozzano (MI), Italy; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele-Milan, Italy.

Background: The standard of care for elderly, newly-diagnosed glioblastoma patients consists, if feasible, of surgical resection followed by a short course of radiation therapy (RT) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT). To date, the literature lacks of consistence in the definition of elderly, if older than 65 years, or 70 years. Aim of this study was to explore whether differences exist between these two cohorts, comparing outcomes using a propensity score matched analysis (PSM).

Materials And Methods: Two hundred twenty-one elderly newly diagnosed glioblastoma patients were included. All patients received surgery followed by RT with concurrent and adjuvant TMZCHT. The RT dose prescribed was 60 Gy/30 fractions for patients 65-69-year-old or 40.5 Gy/15 fractions for ≥70-year-old. After 1:1 matching there were 86 patients in each group. Distribution of covariates was adequately balanced in the matched data set.

Results: After PSM median PFS time, 1,2,3-year PFS rates were 10 months, 33.3%, 13.1%, and 6.6% for the 65-69-year group, 9 months, 34.7%, 11% and 4.8% for the ≥70-year group (p = 0.530). Median OS time, and 1,2,3-year OS rates were 14 months, 54.1%, 23.4%, 13.9% for the 65-69-year old group, and 12 months, 49.3%, 21.5%, 10% for the ≥70-year group (p = 0.357). No differences were recorded in relation to different groups of age.

Conclusions: The PSM analyses showed a similar outcome in 65-69-year old patients compared to older ones notwithstanding a more burdensome RT schedule. Hypofractionated RT treatment has to be considered also in this group of younger elderly, newly-diagnosed GBM patients.
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http://dx.doi.org/10.1016/j.radonc.2020.11.022DOI Listing
March 2021

Anaplastic Astrocytoma: State of the art and future directions.

Crit Rev Oncol Hematol 2020 Sep 17;153:103062. Epub 2020 Jul 17.

Department of Oncology, Oncology 1, Veneto Institute of Oncology - IRCCS, Padua, Italy.

Anaplastic Astrocytoma(AA) is a malignant, diffusely infiltrating, primary brain tumor. According to the WHO 2016 classification of central-nervous-system tumors, AA has been described as a glial tumor with no co-deletion of 1p/19q, and is divided into IDH mutated tumor, characterized by better prognosis, and IDH wild-type form, with worse prognosis. The standard of care is maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Several efforts have been made to evaluate, according to molecular selection, which is the best post-surgical treatment. At recurrence, the treatment remains challenging and some trials are ongoing to evaluate new potential drugs, alone or in combination with chemotherapy. We performed a description of the status of the art on diagnosis, molecular characteristics and treatment of AA. In particular, we focused our details on new drugs; indeed, a deeper knowledge of the molecular characteristics of gliomas could lead to to development of active personalized treatments according with precision medicine.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103062DOI Listing
September 2020

Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions.

Neuro Oncol 2020 11;22(11):1614-1624

Inserm Unit 1127, Sorbonne University, Institute of the Brain and Spinal Cord, Paris, France.

Background: Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.

Methods: We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort.

Results: We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04).

Conclusion: F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.
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http://dx.doi.org/10.1093/neuonc/noaa121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690363PMC
November 2020

Long-course temozolomide in aggressive pituitary adenoma: real-life experience in two tertiary care centers and review of the literature.

Pituitary 2020 Aug;23(4):359-366

Endocrinology Unit, Department of Medicine (DIMED), Padua University Hospital, 35121, Padua, Italy.

Purpose: Aggressive pituitary adenomas (APAs) and pituitary carcinomas (PCs) are challenging for their invasive nature, resistance to treatment and recurrences. Temozolomide (TMZ) is used with benefit and well-tolerated toxicity profile in APAs and PCs. In most studies patients received ≤ 12 cycles but the best length of treatment is debated since other options after discontinuation are scarce and a second course is mainly unsuccessful.

Methods: We report outcomes of 8 patients with APAs and PCs treated with TMZ for more than 12 continuous cycles with a literature review. Data were retrospectively collected from Padua and Milan University Hospitals. TMZ was used as a single agent (150-200 p.o. mg/m2 daily, 5/28 days) for 14 to 45 cycles.

Results: Eight patients (7 M), 7 APAs and 1 PC. Previous treatments included neurosurgery and radiotherapy in all cases except two giant masses (ACTH-silent APA and prolactinoma). No patient had progression disease (PD) during long-term treatment nor toxicities. No one had complete response (CR) but four had partial response (PR). Four ACTH+ tumors maintained stable disease (SD) but the secretion pattern improved in all. After drug withdrawal, three had delayed PD (2 after 18 and one after 29 months, all ACTH+); two are still in SD.

Conclusions: TMZ may be useful and well-tolerated in APAs and PCs as a long-term therapy. PR appears within the first cycles with no escape throughout the treatment; most patients achieve SD. We suggest extended protocols particularly in responsive ACTH+  PAs and PCs, when further therapies may be unsuccessful.
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http://dx.doi.org/10.1007/s11102-020-01040-4DOI Listing
August 2020

Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults.

Neuro Oncol 2020 07;22(7):993-1005

Department of Neurosurgery, University Hospital Group for Psychiatry and Neurosciences (GHU)-Sainte-Anne Hospital, Paris, France.

Background: We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y).

Methods: This work employed a retrospective bicentric cohort study (2010-2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate.

Results: We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P < 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P < 0.001), and in grade II oligodendrogliomas (0.0%; P < 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P < 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041).

Conclusions: The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count.
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http://dx.doi.org/10.1093/neuonc/noaa022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339891PMC
July 2020

Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients.

Cancers (Basel) 2019 Oct 9;11(10). Epub 2019 Oct 9.

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.

Treatment of elderly glioblastoma patients (EGP) is a challenge in neuro-oncology. The comprehensive geriatric assessment (CGA) is currently used to assess geriatric oncological patients with other types of tumors. We performed a large retrospective study to analyze its predictive role in EGP. Patients aged ≥65 years with histologically confirmed diagnosis of glioblastoma were enrolled. CGA included the following tests: the Cumulative Illness Rating Scale-Comorbidity and Severity Index, Activities of Daily Living, Instrumental Activities of Daily Living, the Mini Mental State Examination, and the Geriatric Depression Scale. Based on CGA results, each patient was categorized as fit, vulnerable, or frail. We enrolled 113 patients. According to the CGA scores, 35% of patients were categorized as "fit", 30% as "vulnerable", and 35% as "frail" patients. Median overall survival was 16.5, 12.1, and 10.3 months in fit, vulnerable, and frail patients ( = 0.1), respectively. On multivariate analysis, the CGA score resulted an independent predictor of survival; indeed, vulnerable and frail patients had a hazard ratio of 1.5 and 2.2, respectively, compared to fit patients ( = 0.04). No association between CGA and progression-free survival (PFS) was demonstrated. : The CGA score proved to be a significant predictor of mortality in EGP, and it could be a useful treatment decision tool.
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http://dx.doi.org/10.3390/cancers11101509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826848PMC
October 2019

A multicenter real-world study of bevacizumab in heavily pretreated malignant gliomas: clinical benefit is a plausible end point?

Future Oncol 2019 May 12;15(15):1717-1727. Epub 2019 Apr 12.

Neuroncology Unit, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53 00144, Rome, Italy.

This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG).  The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.
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http://dx.doi.org/10.2217/fon-2018-0826DOI Listing
May 2019

Comparison Between 18F-Dopa and 18F-Fet PET/CT in Patients with Suspicious Recurrent High Grade Glioma: A Literature Review and Our Experience.

Curr Radiopharm 2019 ;12(3):220-228

Oncology 1 Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.

Purposes: The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG.

Methods: We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data.

Results: Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%.

Conclusion: 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG.
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http://dx.doi.org/10.2174/1874471012666190115124536DOI Listing
February 2020

Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial.

Lancet Oncol 2019 01 3;20(1):110-119. Epub 2018 Dec 3.

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. Electronic address:

Background: Glioblastoma is a highly vascularised tumour and there are few treatment options after disease recurrence. Regorafenib is an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases. We aimed to assess the efficacy and safety of regorafenib in the treatment of recurrent glioblastoma.

Methods: REGOMA is a randomised, multicentre, open-label phase 2 trial done in ten centres in Italy. Eligible patients (aged ≥18 years) with histologically confirmed glioblastoma, Eastern Cooperative Oncology Group performance status 0 or 1, and documented disease progression after surgery followed by radiotherapy and temozolomide chemoradiotherapy were randomly assigned (1:1) by a web-based system, stratified by centre and surgery at recurrence (yes vs no), to receive regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle or lomustine 110 mg/m once every 6 weeks until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02926222, and is currently in follow-up.

Findings: Between Nov 27, 2015, and Feb 23, 2017, 124 patients were screened and 119 eligible patients were randomly assigned to receive regorafenib (n=59) or lomustine (n=60). Median follow-up was 15·4 months (IQR 13·8-18·1). At the analysis cutoff date, 99 (83%) of 119 patients had died: 42 (71%) of 59 in the regorafenib group and 57 (95%) of 60 in the lomustine group. Overall survival was significantly improved in the regorafenib group compared with the lomustine group, with a median overall survival of 7·4 months (95% CI 5·8-12·0) in the regorafenib group and 5·6 months (4·7-7·3) in the lomustine group (hazard ratio 0·50, 95% CI 0·33-0·75; log-rank p=0·0009). Grade 3-4 treatment-related adverse events occurred in 33 (56%) of 59 patients treated with regorafenib and 24 (40%) of 60 with lomustine. The most frequent grade 3 or 4 adverse events related to regorafenib were hand-foot skin reaction, increased lipase, and blood bilirubin increased (in six [10%] of 59 patients each). In the lomustine group, the most common grade 3 or 4 adverse events were decreased platelet count (eight [13%] of 60 patients), decreased lymphocyte count (eight [13%]), and neutropenia (seven [12%]). No death was considered by the investigators to be drug related.

Interpretation: REGOMA showed an encouraging overall survival benefit of regorafenib in recurrent glioblastoma. This drug might be a new potential treatment for these patients and should be investigated in an adequately powered phase 3 study.

Funding: Veneto Institute of Oncology and Bayer Italy.
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http://dx.doi.org/10.1016/S1470-2045(18)30675-2DOI Listing
January 2019

Good tolerability of maintenance temozolomide in glioblastoma patients after severe hematological toxicity during concomitant radiotherapy and temozolomide treatment: report of two cases.

Anticancer Drugs 2018 10;29(9):924-928

Department of Oncology, Medical Oncology 1.

Glioblastoma is the most common and aggressive primitive brain tumor in adults. Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ has become the standard treatment. Although TMZ treatment has been considered to have a low toxicity profile, studies have noted the development of a severe myelosuppression, especially during the concomitant treatment; this toxicity may in some cases be prolonged and consequently treatment must be definitively discontinued. We analyzed two cases treated at our oncological center who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy treatment with TMZ. Hypothesizing that radiation therapy and daily TMZ could be the major causes of severe hematological toxicity during the concomitant phase, we decided to treat both patients with maintenance TMZ at the time of recovery of hematological values. Patients showed good tolerability without important myelosuppression. In conclusion, we suggest that glioblastoma patients with severe myelotoxicity during daily TMZ and radiation therapy be treated with maintenance TMZ at the time of blood value recovery.
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http://dx.doi.org/10.1097/CAD.0000000000000678DOI Listing
October 2018

Quality of Life Perception, Cognitive Function, and Psychological Status in a Real-world Population of Glioblastoma Patients Treated With Radiotherapy and Temozolomide: A Single-center Prospective Study.

Am J Clin Oncol 2018 12;41(12):1263-1271

Department of Clinical and Experimental Oncology, Medical Oncology 1 Unit.

Background: Health-related quality of life (HRQoL), cognitive function, and psychological status represent an important focus during the treatment of glioblastoma patients. Nevertheless, few randomized, prospective clinical trials have analyzed these factors, and very little is known in the real-clinical world. We evaluated these characteristics in glioblastoma patients treated with standard first-line therapy outside clinical trials.

Patients And Methods: In total, 111 newly, histologically diagnosed glioblastoma patients treated at our oncology center with radiotherapy and temozolomide were prospectively enrolled. No patient was enrolled in an experimental clinical trial. We assessed HRQoL, cognitive function, and psychological status before starting treatment, at the end of radiotherapy, and every 3 months until 9 months after the end of radiotherapy using EORTC QLQ-C30, BN20, MMSE, and HADS questionnaires.

Results: Global health status, physical, cognitive, and social functioning remained unchanged throughout the study period. A statistically significant change was found in emotional functioning as well as a clinically meaningful amelioration in role functioning between the baseline assessment and 9 months after radiotherapy. Patients older than 65 years reported greater impairment on the bladder control scale than younger patients. When considering tumor location, global health status, communication deficit, and drowsiness, scores were significantly different between the right and left hemispheres. Female patients had a clinically relevant lower score for physical functioning at baseline and 3 months after radiation therapy. Female patients also had a clinically relevant lower depression score at 9 months after radiation therapy.

Conclusions: In routine neurooncology practice, HRQoL, cognitive function, and psychological status did not worsen during first-line treatment in glioblastoma patients receiving standard radiotherapy and temozolomide treatment. However, some patient subgroups, such as elderly and female patients, may have different experiences with treatment, and further investigation is required.
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http://dx.doi.org/10.1097/COC.0000000000000459DOI Listing
December 2018

Effectiveness of antiangiogenic drugs in glioblastoma patients: A systematic review and meta-analysis of randomized clinical trials.

Crit Rev Oncol Hematol 2017 Mar 30;111:94-102. Epub 2017 Jan 30.

Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology, IOV - IRCCS, Padua, Italy.

Background: glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients.

Patients And Methods: we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases.

Results: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). Bevacizumab did not improve overall survival. Twelve trials (4113 patients) were analyzed for progression-free survival. Among antiangiogenic drugs, only bevacizumab demonstrated an improvement of progression-free survival (HR=0.63, p<0.001), both alone (HR=0.60, p=0.003) or in combination to chemotherapy (HR=0.63; p<0.001), both as first-line treatment (HR=0.70, p<0.001) or in recurrent disease (HR=0.52, p<0.001).

Conclusions: antiangiogenic drugs did not improve overall survival in glioblastoma patients, either as first or second-line treatment, and either as single agent or in combination with chemotherapy. Among antiangiogenic drugs, only bevacizumab improved progression-free survival regardless of treatment line, both as single agent or in combination with chemotherapy.
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http://dx.doi.org/10.1016/j.critrevonc.2017.01.018DOI Listing
March 2017

Clinical outcome of an alternative fotemustine schedule in elderly patients with recurrent glioblastoma: a mono-institutional retrospective study.

J Neurooncol 2016 07 11;128(3):481-6. Epub 2016 May 11.

Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata 64, 35128, Padua, Italy.

The optimal treatment of recurrent glioblastoma (GBM) in elderly patients is unclear. Fotemustine (FTM) is a third-generation nitrosourea showing efficacy in gliomas and it has been used with different schedules in adult patients. We performed, for the first time anywhere, a mono-institutional retrospective study to analyze the clinical outcome of an alternative fotemustine schedule in elderly patients with recurrent GBM. Retrospectively, we analyzed all GBM patients 65 years or older previously treated with the combination of radiation therapy and temozolomide (TMZ), receiving an alternative FTM schedule as second-line treatment at our Oncological Center from October 2011 to October 2014 with an ECOG PS ≤ 2. FTM was administrated at 80 mg/m(2) every 2 weeks for five consecutive administrations (induction phase), and then every 4 weeks at 80 mg/m(2) as maintenance. We enrolled 44 patients, 33 males and 11 females; average age was 70 years. ECOG PS was 0-1 in 80 % of the patients. 38 patients relapsed during temozolomide (TMZ) therapy. MGMT methylation status was analyzed in 34 patients and MGMT was methylated in 53 % of the patients. The median progression free survival (PFS) and overall survival (OS) from FTM treatment was 4.1 months (95 % CI 3.1-5.2) and 7 months (95 % CI 5.2-8.4), respectively. Patients with MGMT methylated status and patients who relapsed after completing TMZ therapy had a longer PFS and OS from the beginning of FTM. Thrombocytopenia was the most frequent grade 3-4 haematological toxicity (9 %). The alternative schedule of FTM may be an active and safe treatment for elderly patients with recurrent glioblastoma, especially patients with methylated MGMT and who relapsed after completing temozolomide therapy.
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http://dx.doi.org/10.1007/s11060-016-2136-7DOI Listing
July 2016

Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).

J Neurooncol 2015 Nov 30;125(2):359-67. Epub 2015 Sep 30.

Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy.

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.
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http://dx.doi.org/10.1007/s11060-015-1923-xDOI Listing
November 2015

Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients with isocitrate dehydrogenase-mutated glioma.

Oncologist 2015 May 10;20(5):562-7. Epub 2015 Apr 10.

Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.

Background: Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma.

Materials And Methods: All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry.

Results: A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment.

Conclusion: Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.
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http://dx.doi.org/10.1634/theoncologist.2014-0266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425377PMC
May 2015

An overview of fotemustine in high-grade gliomas: from single agent to association with bevacizumab.

Biomed Res Int 2014 31;2014:698542. Epub 2014 Mar 31.

Medical Oncology 1 Unit, Venetian Oncology Institute-IRCCS, Via Gattamelata 64, 35128 Padua, Italy.

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.
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http://dx.doi.org/10.1155/2014/698542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988896PMC
December 2014

Cisplatin and temozolomide combination in the treatment of supratentorial anaplastic ependymoma.

Chemotherapy 2013 31;59(3):176-80. Epub 2013 Oct 31.

Medical Oncology 1, Veneto Institute of Oncology - IRCCS, Padua, Italy.

Anaplastic ependymomas are rare tumors in adult patients. Maximal safe resection and use of radiation therapy are standard treatment approaches in patients with anaplastic ependymoma. Recurrent anaplastic ependymomas are treated by reoperation when the tumors are surgically accessible, by radiotherapy if not previously administered and by salvage chemotherapy. However, the role of chemotherapy is still unclear. A few retrospective studies showed interesting results with platinum-based regimens, while the administration of temozolomide alone demonstrated conflicting results. We present, for the first time, the case of a patient with anaplastic ependymoma refractory to platinum-based chemotherapy and temozolomide only, but showing a prolonged reduction of the lesion after receiving combination chemotherapy with cisplatin and temozolomide. A brief review of the literature on the treatment of anaplastic ependymoma follows.
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http://dx.doi.org/10.1159/000355662DOI Listing
July 2014