Giuseppe Lombardi

• MD, PhD
• Medical Oncologist, PhD at Istituto Oncologico Veneto

Purpose Bevacizumab is an anti-angiogenetic treatment that can be used in patients with recurrent glioblastoma, but there are limited and controversial data on the optimal dose and schedule, associated toxicities and survival benefits of different doses. Methods A retrospective analysis of patients with recurrent IDHwt glioblastoma treated with be...

A large literature assessed the relationships between the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and glioblastoma location with inconsistent results. Studies assessing this association using the percentage of methylation are lacking. This cross-sectional study aimed at investigating relationships between glioblast...

BACKGROUND Although less than 5% and 1.5% of glioblastomas (GBM) exhibit the BRAFV600E mutation and NRTK fusion, respectively, these cases are significant because some of these patients (pts) may respond well to BRAF/MEK and NTRK inhibitors. Given limited literature, this study aims to evaluate the efficacy of dabrafenib-trametinib and larotrectini...

BACKGROUND Patients with rGBM have a dismal prognosis. Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. No clinical or molecular factors have been validated as predictors of efficacy to second-line therapy. PTEN mutations are common in GBM...

BACKGROUND Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors of efficacy are lacking. We aimed to develop a multi-classification ML algorithm to predict the response to different second line therapies. MATERIAL AND METHODS We c...

BACKGROUND The 2021 WHO Classification defines IDH-wildtype (IDHwt) astrocytomas with either EGFR amplification, pTERT mutation or +7/-10 chromosomal changes as molecularly-defined glioblastomas (mGBMs), even if histologically grade 2. However, it is not clear whether mGBMs share the same clinical characteristics, response to treatments and prognos...

BACKGROUND NGS panels in oncology offer personalized therapies based on genomic alterations, but data on their clinical use and efficacy for non-glioblastoma CNS tumors is limited. MATERIAL AND METHODS This study aimed to explore the molecular landscape of non-glioblastoma CNS tumors in patients (pts) who underwent FoundationOne®CDx testing betwee...

BACKGROUND Defined by a reduced physiological resilience and an increased vulnerability to stressors, frailty is associated with aging and an higher probability of sickness and mortality risk. Influence of frailty on adverse outcomes and survival following craniotomy for glioblastoma is not well documented. Identifying risk factors for complication...

The standard of care for adult patients with gliomas, glioneuronal, and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment; however, the predictive significance of most of the targets for treatment in systemic cancer is less w...

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory diseas...

Despite the implementation of multimodal treatments after surgery, glioblastoma (GBM) remains an incurable disease, posing a significant challenge in neuro-oncology. In this clinical setting, local therapy (LT), a developing paradigm, has received significant interest over time due to its potential to overcome the drawbacks of conventional therapy...

Background The World Health Organization (WHO) 2021 classification of central nervous system (CNS) tumors classified astrocytoma isocitrate dehydrogenase-mutant (A IDHm) with either microvascular proliferation and/or necrosis or homozygous deletion of CDKN2A/B as CNS grade 4 (CNS WHO G4), introducing a distinct entity and posing new challenges to p...

Introductory paragraph Data on the use of targeted therapies in glioma are still limited and the identification of useful targetable mutations is still under investigation. Among all the relevant alterations identified through next generation sequencing (NGS) tests, ROS1 alterations can rarely be found in gliomas, and the most common of them is GOP...

Background In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. Patients and methods The major inclusion criteria were histologically confirmed diagnosis of gliob...

Purpose Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and chemotherapy even if only a few retrospective studies assessed the impact on overall survival (OS) of these approaches. Methods We carried out an Italian multicentric retrospective study of adult patients with H3K27-altered DMG to as...

Background We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using 3 main classes and a total of 5 subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II tria...

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium...

Introduction Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter. Methods This was a multicenter phase I...

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Standard therapies, including surgical resection, chemoradiation, and tumor treating fields, have not resulted in major improvements in the survival outcomes of patients with GBM. The lack of effective strategies has led to an increasing interest in immunotherapic a...

Ependymomas are rare glial tumors with clinical and biological heterogeneity, categorized into supratentorial ependymoma, posterior fossa ependymoma, and spinal cord ependymoma, according to anatomical localization. Spinal ependymoma comprises four different types: spinal ependymoma, spinal ependymoma MYCN-amplified, myxopapillary ependymoma, and s...

BACKGROUND in the randomized phase 2 REGOMA trial, regorafenib (REG) showed promising activity in recurrent glioblastoma (GBM) patients (PTS); subsequently, in Italy the National Health System has permitted the reimbursement of the REG as second-line therapy. We performed a large multicenter, prospective and observational study to confirm REGOMA da...

INTRODUCTION The multikinase inhibitor regorafenib improved overall survival (OS) versus lomustine in relapsed GBM in the randomized phase 2 REGOMA study. The aim of this study was to evaluate the efficacy of regorafenib combined with nivolumab in this setting (NCT04704154). METHODS Patients aged ≥ 18 years with recurrent GBM/AA (WHO 2016 classifi...

The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for more effective therapies, particularly for GBMs with unmethylated MGMT. Drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use for psychiatric disorders, shows...

Importance The prognosis of overall survival (OS) in patients with glioblastoma (GBM) may depend on the underlying structural connectivity of the brain. Objective To examine the association between white matter tracts affected by GBM and patients’ OS by means of a new tract density index (TDI). Design, Setting, and Participants This prognostic st...

Pain is one of the predominant and troublesome symptoms that burden cancer patients during their whole disease trajectory: adequate pain management is a fundamental component of cancer care. Opioid are the cornerstone of cancer pain relief therapy and their skillful management must be owned by physicians approaching cancer pain patients. In light o...

BACKGROUND In the randomized phase 2 REGOMA trial, regorafenib has shown promising activity in recurrent glioblastoma patients with a significantly longer survival compared to the standard lomustine therapy. Subsequently, in Italy regorafenib was approved as second-line therapy by the Italian Medicines Agency. We performed a large multicenter, pros...

BACKGROUND Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. METHODS European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study s...

BACKGROUND The use of next-generation sequencing (NGS) allows the identification of subgroups of patients that may respond to personalized targeted therapies (TT). Despite the acquired deep knowledge about biology, there are only a few data available regarding TT efficacy and feasibility for patients with glioblastoma (GBM). MATERIAL AND METHODS W...

BACKGROUND Ependymoma is a rare disease in adult patients (pts) and there is no standard systemic treatment in recurrent disease after surgery and radiotherapy. We reviewed our cases of confirmed intracranial and spinal ependymomas and described experience of pts treated with systemic therapies at disease recurrence. MATERIAL AND METHODS We retros...

BACKGROUND Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and temozolomide even if only a few retrospective studies assessed the impact on survival of these approaches. MATERIAL AND METHODS We carried out a multicentric retrospective study of adult patients with DMG to assess the effective r...

BACKGROUND Glioblastoma (GBM) is associated with the activation of multiple signaling pathways, including the receptor tyrosine kinases, VEGFR, FGFR and PDGFR. The potential response to anti-angiogenic agents makes GBM an attractive target for regorafenib (REG). Antitumor activity of REG in recurrent GBM patients was shown in the phase II REGOMA tr...

BACKGROUND The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in us...

We retrospectively analyzed 34 patients (pts) [19 males, 15 females, median age 54] with recurrent IDH wildtype glioblastoma treated with target therapy (TT) based on their next-generation sequencing (NGS) profile, between March2020 and December2022 at Veneto Institute of Oncology, Padua (Italy). ECOG PS was 0-1 in 29 pts. All pts received previous...

Background Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain’s functional topological organization and glioblastoma (GBM) location. Furthermore, we asses...

Purpose Regorafenib demonstrated encouraging results in recurrent glioblastoma patients. Some studies showed that changes in circulating thyroid hormones (fT3, fT4, fT3/fT4 ratio) can be considered as prognostic factors in patients with various types of tumors. We designed this study to investigate the relationship between baseline thyroid variable...

2075 Background: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma (Graillon et al. 2021). This classification segregates meningioma response into three main classes and a total of five subclasses (class 1 = volume decrease ≥ 25%; 2A = tumor stabi...

Background: Next-generation sequencing (NGS) panels enable the identification of alterations in cancer-related genes. This may guide a molecularly targeted strategy for the treatment of glioblastoma (GBM). Material and methods: We retrospectively analysed data obtained using FoundationOne®CDx in a large cohort of IDH1/2 wild-type GBM. We aimed t...

Background: The clinical relevance of promoter mutations and single nucleotide polymorphism rs2853669 of telomerase reverse transcriptase (TERT) and telomere length in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients remains unclear. Moreover, some studies speculated that TERT promoter status might influence the p...

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry stu...

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an intercon...

Introduction A minor part of pituitary adenomas show a tendency to grow, despite multimodal treatment. Temozolomide (TMZ) has been used in the last 15 years in patients with aggressive pituitary tumors. TMZ requires a careful balance of different expertise, especially for selection criteria. Areas covered We conducted: 1) a systematic review of th...

Background. Glioblastoma (GBM) is a devastating brain tumor with poor prognosis, characterized by rapid growth and invasion into surrounding brain tissue. It is a hard-to-treat cancer and represents an unmet medical need. In recent years, there has been a growing interest in developing novel approaches to improve the outcomes of GBM patients; among...

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 retrospect...

The prognosis of patients with advanced adrenocortical carcinoma (ACC) is often poor: in the case of metastatic disease, five-year survival is reduced. Advanced disease is not a non-curable disease and, in referral centers, the multidisciplinary approach is the standard of care: if a shared decision regarding several treatments is available, includ...

BACKGROUNDNGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. METHODS From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOne®CDx). We identified all potential act...

BACKGROUND the current standard to treat meningiomas can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We performed a retrospective analysis investigating the efficacy and safety of BEV in meni...

Glioblastoma (GBM) has activation of multiple signaling pathways in the tumor microenvironment, including the receptor tyrosine kinases, VEGFR, FGFR and PDGFR. The potential response to anti-angiogenic agents makes GBM an attractive target for regorafenib (REG). Antitumor activity of REG in recurrent GBM patients was shown in the REGOMA trial. Inte...

Background NGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. Material and Methods From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOne®CDx). We identified all...

Background Glioblastoma is the most frequent CNS malignant tumor, with high aggressiveness and poor prognosis. Regorafenib has recently demonstrated promising activity in terms of survival in recurrent glioblastoma patients. The impact of thyroid function on regorafenib activity has alreasy described in in patients with other types of tumors. This...

Background Angiogenesis is one of the most distinctive hallmarks of glioblastoma (GBM). Although bevacizumab did not show to improve overall survival in phase 3 trials, it was approved by FDA and is often prescribed as off-label therapy in the recurrent clinical setting. The aim of this study is to evaluate the difference in terms of survival and s...

Background meningiomas are the most frequent primary brain tumours. The current standard treatment for atypical and anaplastic meningioma can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We pe...

Background Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite advances in surgical and first-line treatment, all pts relapse. The aim of this study is to evaluate the benefit of metronomic Temozolomide (mTMZ) for recurrent GBM. Material and Methods All pts treated at Veneto Institute of Oncology from September 2013...

We aimed to evaluate the role of adrenal multidisciplinary team evaluation (MTE) in affecting the overall survival (OS) and progression-free survival (PFS) in patients with adrenocortical carcinoma (ACC). We included in a retrospective monocentric study 47 patients with ACC. We divided our cohort into group 1 (without adrenal-MTE discussion, ACC di...

Isocitrate dehydrogenase wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still dismal with a median survival of about 1 year. BRAFV600E mutation, an important target for personalized therapy, has been identified in about 3% of these patients, but few data are available from prospective studies...

Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classific...

Background Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor EGFR gene amplification (EGFR-amp). Preclinical and early phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutan...

Background: Glioblastoma is the most prevalent and severe type of malignant brain tumor in adults. Although the genetic make-up initiating glioblastoma is increasingly better understood, a better understanding in the mechanisms that drive its evolution, heterogeneity and therapy resistance may reveal new directions for therapy development. To get b...

3139 Background: NGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. Methods: From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOneCDx). We identified all potenti...

TPS2073 Background: The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medicat...

Background: O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods: We evaluated g...

Simple Summary Glioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient su...

Background Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and...

PurposeDiffuse gliomas are the most common primary malignant brain tumors in adults. Many studies analyzed their epidemiology, such as the incidence and mortality. Moreover, the identification of their risk factors is still controversial and to date we have only a few accepted and confirmed risk factors. In the last few years, many molecular marker...

Simple Summary Mutations of isocitrate dehydrogenase (IDH) genes are the distinctive genetic feature of lower-grade gliomas (LGGs). Tumor-associated IDH1/2 mutations result in a loss of normal enzymatic function and the abnormal production of 2-hydroxyglutarate (2-HG), which acts as an oncometabolite causing widespread changes in histone and DNA me...

Simple Summary Diffuse gliomas, including the most aggressive subtype glioblastoma, represent the most frequent primary central nervous system tumors. Despite intense chemoradiation protocols that represent the current standard of care, these cancers inevitably recur, and median overall survival does not exceed 18 months. New therapeutic options ar...

Background Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grad...

The cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Peripheral blood and tissue specimens from the central and...

Ependymomas are rare primary central nervous system tumors. They can form anywhere along the neuraxis, but in adults, these tumors predominantly occur in the spine and less frequently intracranially. Ependymal tumors represent a heterogenous group of gliomas, and the WHO 2016 classification is based essentially on a grading system, with ependymomas...

BACKGROUND the significance of TERT promoter mutations, telomere length and their interactions with MGMT methylation status in patients with IDH-wildtype GBM patients remain unclear. We performed a monoinstitutional study to better investigate their impact and their interaction on clinical outcomes. METHODS TERTmutations (C228T and C250T), relativ...

The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use since six...

INTRODUCTION Regorafenib (REG), an oral multikinase inhibitor, showed benefit in recurrent GBM (recGBM) patients in the REGOMA trial. We investigated the clinical outcome and safety of REG in a real-life population of recGBM patients treated at Veneto Institute of Oncology as off-label use. MATERIAL AND METHODS Patients receiving REG were entered...

BACKGROUND Despite advances in surgical and first-line treatment, all glioblastoma pts relapse. The aim of this study is to evaluate the benefit of metronomic temozolomide (mTMZ) for recurrent glioblastoma. METHODS 120 pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion crite...

Objectives The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to...

Background No systemic treatment has been established for meningioma progressing after local therapies. Methods This randomized, multicenter, open-label, phase 2 study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m 2 every three weeks) or local standard o...

Background Prognostic factors and role of treatments are not well known in isocitrate dehydrogenase (IDH) wild-type (wt) grade 2 astrocytomas. The aim of this study was to define in these tumours clinical features, molecular characteristics and prognostic factors, with particular focus on molecular subgroups defined by cIMPACT-NOW update 3. Method...

Background: EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being amongst its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signalling compared with wildtype EGFR. Methods: To better understand the on...

Despite multimodal treatment with surgery and radiochemotherapy, the prognosis of glioblastoma remains poor, and practically all glioblastomas relapse. To date, no standard treatment exists for recurrent glioblastoma patients and traditional therapies have showed limited efficacy. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor show...

BACKGROUND Oligodendroglioma (OD) is defined by the presence of both IDH1/2 mutation and 1p/19q codeletion. Although prognosis of OD patients is relatively favorable, tumours usually relapse and often evolve to a higher malignancy grade, with some acquiring the treatment induced hypermutated phenotype. To better understand how these tumours evolve...

BACKGROUND Regorafenib (REG), an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases showed encouraging benefit in recurrent GBM patients enrolled in the randomized, phase 2 REGOMA trial. We investigated the clinical outcome and safety of REG in a real-life population of recurrent glioblastoma patients treated...