Real-world management and long-term outcomes in adolescent, young adult, and adult medulloblastoma: Experience from a monocentric series with multimodal and targeted approaches Alberto Bosio, Marta Maccari, Marta Padovan, Mario Caccese, Maital Bolshinsky, Antonella Galiano, Francesco Cavallin, Luisa Bellu, Francesco Pasqualetti, Alessandro Parisi, Giovanni Librizzi, Giovanna Pintacuda, Alessandro Salvalaggio, Marco Zoccarato, Tamara Ius, Francesco Volpin, Luca Denaro, Sara Lonardi, Giuseppe Lombardi Neuro Oncology Practice, 2026 Abstract Background Medulloblastoma (MB) is an exceedingly rare malignancy in adolescents and young adults (AYA) and adults. This study aims to describe clinical characteristics, treatments, including the use of targeted therapy, outcomes, and long-term sequelae in a single-center cohort of AYA/adult MB patients. Methods We retrospectively analyzed MB patients aged ≥16 years treated at Veneto Institute of Oncology, Padua, Italy, between 2011 and 2025. Clinical, molecular, and treatment data were collected. Treatment response was assessed using RAPNO criteria, and treatment-related toxicity according to CTCAE v5.0. Survival outcomes were estimated using the Kaplan-Meier method. Results We included 29 patients. At diagnosis, 86% were symptomatic, 55% had an ECOG performance status (PS) of 0, and desmoplastic/nodular was the most frequent histology (48%). Molecular subgrouping was available in 45%, with SHH activation as the most common subgroup (31%, 9/29 patients). All patients underwent craniospinal radiotherapy; adjuvant chemotherapy regimens included cisplatin-etoposide±cyclophosphamide (62%), cisplatin-lomustine±vincristine (21%), and intensive pediatric regimens (10%), while 2 patients (7%) did not receive chemotherapy due to comorbidities. First-line complete response was achieved in 65%. Overall, 38% experienced progression, and 24% died. Three patients received vismodegib at recurrence. Three-year PFS and OS rates were 78% and 92%. Stratified analyses indicated worse outcomes in patients with high-risk classification, subtotal resection, and lower baseline ECOG PS. Grade 3-4 toxicity occurred in 30%. Long-term complications included neurocognitive impairment (21%) and radiotherapy-induced secondary malignancies (10%). Conclusions Long-term survivorship is often achievable in AYA/adult MB, though late toxicities remain a concern. Molecular profiling supports risk stratification and therapy personalization. Long-term toxicities highlight the need for de-intensified strategies.
TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas Youri Hoogstrate, Santoesha A. Ghisai, Levi van Hijfte, Rania Head, Iris de Heer, Marta Padovan, Maurice de Wit, Wies R. Vallentgoed, Angelo Dipasquale, Maarten M.J. Wijnenga, Bas Weenink, Rosa Luning, Sybren L.N. Maas, Adela Brzobohata, Michael Weller, Tobias Weiss, Maximilian J. Mair, Anna S. Berghoff, Adelheid Wöhrer, Albert Jeltsch, Johan A.F. Koekkoek, Hans M. Hazelbag, Mathilde C.M. Kouwenhoven, Yongsoo Kim, Bart A. Westerman, Bauke Ylstra, Anneke M. Niers, Kevin C. Johnson, Frederick S. Varn, Roel G.W. Verhaak, Mustafa Khasraw, Martin J. van den Bent, Pieter Wesseling, Pim J. French Cell Reports Medicine, 2026 ) that captures these changes and outperforms the World Health Organization (WHO) grading for oligodendrogliomas. Our findings underscore the potential of DNA methylation-based grading to more accurately reflect tumor biology and inform clinical decision-making in IDH-mutant gliomas.
Targeted therapies in optic pathway gliomas Edoardo Agosti, Pier Paolo Panciani, Giuseppe Lombardi, Matthias Preusser, Giorgia De Rosa, Karen Mapelli, Amedeo Piazza, Daniele Tognetto, Caterina Gagliano, Luca Denaro, Marta Padovan, Marco Maria Fontanella, Marco Zeppieri, Tamara Ius Cancer Treatment Reviews, 2026 AIM: This study provides a systematic synthesis of current evidence on targeted therapies for optic pathway gliomas (OPGs), emphasizing their molecular rationale, clinical effectiveness, safety profiles, relevance in both Neurofibromatosis type 1 (NF1) -associated and sporadic cases. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines using PubMed, Web of Science, and Scopus databases up to April 2025. Eligible studies focused on systemic targeted therapies for OPGs, evaluating efficacy, molecular targets, and adverse events. Both preclinical and clinical data were included, with study quality assessed using the Newcastle-Ottawa Scale. RESULTS: Of 414 records screened, 13 studies (11 clinical and 2 preclinical) met inclusion criteria. Targeted agents included MEK inhibitors, mTOR inhibitors, anti-VEGF agents, and BRAF inhibitors. MEK inhibitors showed promising progression-free survival outcomes, particularly in NF1-associated OPGs, while anti-VEGF therapies rapidly improved visual symptoms in select cases. MEK inhibitors showed the most consistent progression-free survival benefits, particularly in NF1-associated OPGs, with selumetinib emerging as the leading agent with favorable efficacy and safety profiles. These findings support the growing role of biomarker-driven targeted strategies while underscoring unresolved challenges related to long-term safety and optimal treatment duration. CONCLUSION: Targeted therapies constitute a potentially paradigm-shifting development in the management of OPGs, enhancing disease control while improving the prospects for long-term visual preservation. This review underscores the need for individualized, biomarker-driven approaches and highlights challenges including resistance, long-term safety, and therapy duration.
Targeted and systemic therapies for recurrent adult ependymomas: real-world outcomes from a single institution and concise literature review Marta Maccari, Alberto Bosio, Mario Caccese, Marta Padovan, Angela Guerriero, Giovanni Librizzi, Giovanna Pintacuda, Luisa Bellu, Alba Fiorentino, Francesco Volpin, Tamara Ius, Franco Chioffi, Luca Denaro, Sara Lonardi, Giuseppe Lombardi Frontiers in Oncology, 2026 Background Recurrent adult ependymomas lack standard systemic therapies and evidence on chemotherapy and targeted agents is limited. This study aimed to retrospectively evaluated outcomes of systemic therapies, including targeted combinations, in a real-world cohort. Methods Adult patients with intracranial or spinal ependymoma treated at our institution between 2013 and 2025 who received at least one systemic line at recurrence were included. Tumor response was assessed according to RANO criteria. Primary endpoints were disease control rate (DCR) and progression-free survival (PFS). Secondary endpoints were overall survival from the start of the first line treatment (OSt) and overall survival from diagnosis (OS). Results Among 47 patients, 12 received systemic therapy at recurrence. The median follow up duration for the entire cohort was 28.3 months. Temozolomide (TMZ) was the most commonly used agent (n=12). TMZ monotherapy achieved a DCR of 57% with 6- and 12-month PFS rates of 85.7% and 57.1%, respectively. Targeted therapy was administered to 7 patients: the TMZ-Lapatinib combination provided limited benefit (DCR 33%, median PFS 2.9 months), bevacizumab-based regimens showed variable efficacy; bevacizumab alone achieved a DCR of 33% with one case of prolonged stabilization (>58 months), while bevacizumab plus fotemustine yielded a PFS of 14.1 months. Treatments were generally well tolerated, with limited grade 3 toxicities. Sequential systemic therapy, up to five lines, was feasible in selected cases. Median OSt was not reached; 12-month OS was 66.7%. Conclusions This real-world analysis indicates that temozolomide is feasible and associated with disease stabilization in selected patients, while bevacizumab-based combinations showed signals of clinical activity in recurrent adult ependymomas. Prospective, biomarker-driven multicenter trials are warranted to optimize systemic strategies in this rare disease.
Prolonged sequential temozolomide in glioblastoma: A systematic review with exploratory quantitative synthesis F. Pasqualetti, T. Ius, N. Montemurro, C. Bertolotti, S. Pivato, M. Padovan, M. Caccese, L. Bellu, R. Morganti, F. Acerbi, L. Denaro, R. Soffietti, D. Ottaviani, G. Bocci, G. Lombardi, M. Krengli Cancer Treatment and Research Communications, 2026 BACKGROUND: In patients with glioblastoma (GBM), the optimal number of adjuvant temozolomide (TMZ) cycles following combined radio-chemotherapy remains uncertain. This study aimed to synthesize the available randomized evidence addressing treatment duration. METHODS: Following PRISMA 2020 recommendations, we conducted a systematic review with exploratory quantitative synthesis of prospective randomized trials in newly diagnosed GBM. Studies were critically appraised with particular attention to survivorship bias, post-randomization selection, molecular heterogeneity, and trial design. Quantitative synthesis was based on reported median overall survival (OS) values according to planned TMZ duration (6 vs 12 cycles). RESULTS: Nine studies met the inclusion criteria, comprising 7 studies with planned 6-cycle TMZ (965 patients) and 5 studies with planned 12-cycle TMZ (504 patients). Across studies, prolonged TMZ was not associated with a clear survival advantage. Pooled median OS was 17.10 months for six cycles and 17.64 months for twelve cycles, however, with no statistically significant difference. Studies reporting apparent benefit were consistently affected by post-six-cycle selection and survivorship bias. CONCLUSIONS: Current evidence does not allow a definitive determination of the optimal duration of adjuvant TMZ in newly diagnosed GBM. Although extended treatment has been associated with numerically longer survival in some studies, these findings are difficult to interpret due to methodological limitations and heterogeneity. Therefore, it remains uncertain whether prolonging TMZ beyond six cycles provides a meaningful clinical benefit, and treatment decisions should be individualized.
Regorafenib versus local standard of care in patients with grade 2–3 meningioma no longer eligible for loco-regional treatments: a phase II randomized controlled trial (the MIRAGE study) Alberto Bosio, Giulia Cerretti, Marta Padovan, Paola Del Bianco, Maurizio Polano, Susanna Mandruzzato, Stefano Indraccolo, Renzo Manara, Giovanni Librizzi, Mario Caccese, Martina Corrà, Marta Maccari, Sara Lonardi, Gian Luca De Salvo, Giuseppe Lombardi Trials, 2025 BACKGROUND: Regorafenib is an oral multi-tyrosine kinase (RTK) inhibitor. It exhibits high selectivity for VEGFR1/2/3, while also inhibiting PDGFRβ, FGFR1, and oncogenic signaling cascades involving c-RAF/RAF1 and BRAF. These pathways are highly expressed in meningiomas, particularly in high-grade meningiomas. METHODS: The MIRAGE trial (NCT06275919) is a multicenter, open-label, controlled, randomized phase 2 clinical trial evaluating grade 2/3 meningioma patients who have progressed following surgery and radiotherapy. A total of 94 participants are being randomized (1:1) to receive either regorafenib (160 mg orally for 3 weeks on, 1 week off) or local standard-of-care therapies (e.g., bevacizumab, hydroxyurea, somatostatin analogs). Major inclusion criteria include histological confirmation of grade 2 or grade 3 meningioma according to the WHO 2021 classification, radiologically documented progression according to RANO criteria with at least 1 measurable lesion (minimum 10 × 10 mm) on baseline MRI, ineligibility for further surgery and/or radiotherapy, and a WHO performance status of 0-1. The primary endpoint is 6-month progression-free survival (6m-PFS) and secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and health-related quality of life. Exploratory analysis will also be performed. MIRAGE, initiated in September 2024, is an academic trial promoted by the Istituto Oncologico Veneto, IOV-IRCCS, and will recruit patients across 15 neuro-oncology centers in Italy with an estimated study duration of 18 months. DISCUSSION: MIRAGE is a phase 2 trial designed to determine the role of regorafenib in prolonging the PFS of grade 2-3 meningioma patients ineligible for further surgery and/or radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT06275919. Registered before start of inclusion, 7 February 2024. EuCT no. 2024-510954-28.
Tumor-related epilepsy in glioma: A multidisciplinary overview Roberto Michelucci, Giada Pauletto, Antonio Silvani, Elena Pasini, Tamara Ius, Matteo Martinoni, Carlo Alberto Castioni, Andrea Salmaggi, Sofia Asioli, Marta Maschio, Giuseppe Minniti, Enrico Franceschi, Flavio Villani, Roberta Rudà, Eleonora Aronica, and Epilepsia, 2025 Seizures are a common and challenging symptom in brain tumors, affecting approximately 60% of patients. Tumor‐related epilepsy (TRE) in glioma patients requires personalized and dynamic management in a multidisciplinary environment, especially for its intricate pathophysiology and unpredictable disease evolution. This investigation provides an updated overview about the pathophysiological mechanisms and treatment options of TRE associated with gliomas, based on expert contributions belonging to different areas. By combining the most recent discoveries and expert opinions, this study seeks to provide useful advice for TRE management in glioma patients. To improve patient outcomes and quality of life, prospective, standardized, multicentric studies should be promoted to optimize TRE patient care and refine therapeutic approaches.
Bevacizumab in recurrent glioblastoma: does dose matter? Our monocentric and comparative experience Giulia Cerretti, Alberto Bosio, Giovanni Librizzi, Giovanna Pintacuda, Mario Caccese, Alessandro Salvalaggio, Marco Zoccarato, Alessandro Parisi, Marta Padovan, Marta Maccari, Francesco Cavallin, Luisa Bellu, Francesco Pasqualetti, Tamara Ius, Luca Denaro, Francesco Volpin, Marina Coppola, Sara Lonardi, Giuseppe Lombardi Journal of Neuro Oncology, 2025 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 bevacizumab at the Veneto Institute of Oncology was performed. Patients received bevacizumab in 2 different schedules (5 mg/kg or 10 mg/kg q2w), as monotherapy or in combination with chemotherapy. Results 81 patients were analyzed, 33 received bevacizumab 5 mg/Kg, 48 received bevacizumab 10 mg/Kg. Median PFS was 4 months in both patients treated with 5 mg/kg and those treated with 10 mg/kg (p-value=0.08), median OS was 5 months in patients treated with 5 mg/kg and 7 months in those treated with 10 mg/kg (p-value=0.10). There was no difference in the use of steroid therapy between the two groups. The incidence of adverse events was not statistically different. Conclusions There was no statistically significant difference in survival, PFS, response, toxicity and steroid reduction between the two different doses. These results may support the use of lower doses of the drug with comparable benefit for patients and with additional advantage in terms of health care costs.
PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives Eugenia Cella, Alberto Bosio, Pasquale Persico, Mario Caccese, Marta Padovan, Agnese Losurdo, Marta Maccari, Giulia Cerretti, Tamara Ius, Giuseppe Minniti, Ahmed Idbaih, Nader Sanai, Michael Weller, Matthias Preusser, Matteo Simonelli, Giuseppe Lombardi Cancer Treatment Reviews, 2024
The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study Vincenzo Di Nunno, Giuseppe Lombardi, Matteo Simonelli, Giuseppe Minniti, Angela Mastronuzzi, Valentina Di Ruscio, Martina Corrà, Marta Padovan, Marta Maccari, Mario Caccese, Giorgia Simonetti, Arianna Berlendis, Mariangela Farinotti, Bianca Pollo, Manila Antonelli, Antonio Di Muzio, Angelo Dipasquale, Sofia Asioli, Dario De Biase, Alicia Tosoni, Antonio Silvani, Enrico Franceschi Journal of Neuro Oncology, 2024
Spinal ependymoma in adults: from molecular advances to new treatment perspectives Giulia Cerretti, Federico Pessina, Enrico Franceschi, Valeria Barresi, Alessandro Salvalaggio, Marta Padovan, Renzo Manara, Vincenzo Di Nunno, Beatrice Claudia Bono, Giovanni Librizzi, Mario Caccese, Marta Scorsetti, Marta Maccari, Giuseppe Minniti, Pierina Navarria, Giuseppe Lombardi Frontiers in Oncology, 2023
Gliomatosis cerebri: A monocentric real-life experience Luisa Bellu, Mario Caccese, Giulia Cerretti, Franco Berti, Fabio Busato, Alessandro Parisi, Marta Padovan, Vittorina Zagonel, Giuseppe Lombardi Journal of Cancer Metastasis and Treatment, 2021
Clinical management of diffuse low-grade gliomas Giuseppe Lombardi, Valeria Barresi, Antonella Castellano, Emeline Tabouret, Francesco Pasqualetti, Alessandro Salvalaggio, Giulia Cerretti, Mario Caccese, Marta Padovan, Vittorina Zagonel, Tamara Ius Cancers, 2020
Anaplastic Astrocytoma: State of the art and future directions Mario Caccese, Marta Padovan, Domenico D’Avella, Franco Chioffi, Marina Paola Gardiman, Franco Berti, Fabio Busato, Luisa Bellu, Eleonora Bergo, Marco Zoccarato, Matteo Fassan, Vittorina Zagonel, Giuseppe Lombardi Critical Reviews in Oncology Hematology, 2020
Neoplastic Pericardial Effusion: A Monocentric Retrospective Study Elisabetta Di Liso, Alice Menichetti, Maria Vittoria Dieci, Cristina Ghiotto, Alberto Banzato, Alessandra Bianchi, Giovanna Pintacuda, Marta Padovan, Floriana Nappo, Enrico Cumerlato, Federica Miglietta, Eleonora Mioranza, Giulia Zago, Luigi Corti, Valentina Guarneri, Pierfranco Conte Journal of Palliative Medicine, 2019
