Publications by authors named "Vincenzo Di Nunno"

Introduction: Immunotherapy with or without chemotherapy has become standard first line treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), altering the second-line treatment landscape. After progression to first line no standardized systemic treatments have been identified. Advanced lines of therapy in pre-immune checkpoint inhibitors (ICIs) era led to very modest clinical impact.

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Introduction: Sinonasal tumors are rare and heterogeneous malignancies comprising 3-5% of head and neck cancers, often diagnosed at advanced stages due to nonspecific symptoms and anatomical location. Their proximity to critical structures complicates both surgery and radiotherapy. While multimodal treatment is standard, the role of chemotherapy remains unclear.

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Chimeric antigen receptor (CAR)-T cell therapy is emerging as a promising immunotherapeutic modality for improving clinical outcomes in high-grade gliomas. Three recent studies have demonstrated the safety and feasibility of intracranial CAR-T cell administration in patients with glioblastoma (GBM), along with preliminary evidence of rapid but transient objective responses. These findings provide a rationale for further clinical investigation of this approach.

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Drugs targeting mitochondrial energy metabolism are emerging as promising antitumor therapeutics. Glioma treatment is extremely challenging due to the high complexity of the tumor and the high cellular heterogeneity. From a metabolic perspective, glioma cancer cells can be classified into the oxidative metabolic phenotype (mainly depending on mitochondrial respiration for energy production) and glycolytic phenotype or "Warburg effect" (mainly depending on glycolysis).

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: Glioblastoma -wildtype (GBM -wt) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping its tumor microenvironment (TME) regulate tumor progression and treatment response. The aim of this study was to characterize the main immunosuppressive elements of the GBM -wt TME.

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  • A systematic review and meta-analysis revealed that economic income significantly affects the survival rates of glioblastoma patients, with those having lower income experiencing poorer outcomes.
  • The study analyzed 12 research papers, encompassing over 143,000 patients, and found that a lower economic income correlated with a hazard ratio of 1.09, indicating a higher risk of mortality.
  • Factors like the type of healthcare system and the timing of treatment had no significant impact on survival, highlighting the need to address socioeconomic disparities in cancer care to improve outcomes for disadvantaged patients.
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Purpose Of Review: In this review, we investigated the role of European oncological networks on management and care of patients with central nervous system (CNS) malignancies.

Recent Findings: Within this universe of tumors, malignancies of the central nervous system (CNS) malignancies represent a challenge because of several reasons such as biological complexity, the need of dedicated experienced physicians (surgeons, pathologists, radiologists and neuro-oncologists) and tertiary healthcare providers. Limits to the development of effective and innovative care are represented by the rarity of these tumors and their extreme heterogeneity in terms of clinical presentation, course of the disease, genetic assessments and site of presentation.

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  • TP53 mutations are common in patients with IDH-wildtype GBM, but their impact on patient prognosis has not been well studied.
  • This study analyzed 97 patients under 70 years old who received specific treatments and found that 19.4% had TP53 mutations, but this did not significantly affect overall survival rates.
  • Although TP53 mutations didn't correlate with survival for all patients, they were linked to longer survival in a small group with overall survival over 36 months, indicating they might be important for certain long-term survivors.
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Glioneuronal and neuronal tumors are rare primary central nervous system malignancies with heterogeneous features. Due to the rarity of these malignancies diagnosis and treatment remains a clinical challenge. Here we performed a narrative review aimed to investigate the principal issues concerning the diagnosis, pathology, and clinical management of glioneuronal tumors.

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  • Adult Diffuse midline glioma (DMG) is a rare brain tumor in adults, treated primarily with radiotherapy and chemotherapy, but the effectiveness of these treatments has been under-evaluated.
  • A study of 49 patients revealed that while concurrent chemotherapy didn’t improve overall survival (OS), adjuvant temozolomide treatment significantly extended OS from 9.0 to 21.2 months.
  • The results suggest that following initial treatment with radiotherapy, adjuvant chemotherapy can enhance survival outcomes, and for patients who experience disease progression, second-line systemic treatment could offer further survival benefits.
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  • Glioblastoma -wildtype is the most aggressive and common primary brain tumor, with ongoing research uncovering its complex genetic makeup and aggressive behavior.* -
  • The telomerase reverse transcriptase (TERT) gene is frequently mutated in this cancer, found in 80-90% of GBM -wildtype cases, making it a promising target for treatment despite challenges in developing effective inhibitors.* -
  • Recent studies are exploring new immunological methods to inhibit TERT, and this review examines TERT's role in glioblastoma, its inhibition challenges, and potential combination treatment approaches to enhance effectiveness.*
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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 -amplified, myxopapillary ependymoma, and subependymoma. The clinical onset largely depends on the spinal location of the tumor.

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Olfactory neuroblastoma (ONB) is a rare neoplasm originating from the olfactory neuroepithelium representing 3-6% of tumors of the sinonasal tract. ONB require multi-disciplinary care. Historically, the gold standard surgical procedure for ONB has been open craniofacial resection.

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Chimeric antigen receptor (CAR-T) therapy has marked a paradigm shift in the treatment of hematological malignancies and represent a promising growing field also in solid tumors. Neurotoxicity is a well-recognized common complication of CAR-T therapy and is at the forefront of concerns for CAR-based immunotherapy widespread adoption, as it necessitates a cautious approach. The non-specific targeting of the CAR-T cells against normal tissues (on-target off-tumor toxicities) can be life-threatening; likewise, immune-mediate neurological symptoms related to CAR-T cell induced inflammation in central nervous system (CNS) must be precociously identified and recognized and possibly distinguished from non-specific symptoms deriving from the tumor itself.

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The lack of significant improvement in the prognosis of patients with GB over the last decades highlights the need for innovative treatments aimed at fighting this malignancy and increasing survival outcomes. The results of the phase III clinical trial of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccination), which has been shown to increase both median survival and long-term survival in newly diagnosed and relapsed glioblastoma, have been enthusiastically received by the scientific community. However, this study deserves some reflections regarding methodological issues related to the primary endpoint change, the long accrual period, and the suboptimal validity of the external control population used as the comparison arm.

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Gliomas are the most frequent central nervous system (CNS) primary tumors. The prognosis and clinical outcomes of these malignancies strongly diverge according to their molecular alterations and range from a few months to decades. The tumor-associated microenvironment involves all cells and connective tissues surrounding tumor cells.

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Introduction: Glioblastoma (GBM) is the most common primary brain tumor in adults. GBM treatment options have been the same for the past 30 years and have only modestly extended survival, despite aggressive multimodal treatments. The progressively better knowledge of GBM biology and a comprehensive analysis of its genomic profile have elucidated GBM heterogeneity, contributing to a more effective molecular classification and to the development of innovative targeted therapeutic approaches.

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Gliomas are molecularly heterogeneous brain tumors responsible for the most years of life lost by any cancer. High-grade gliomas have a poor prognosis and despite multimodal treatment including surgery, radiotherapy, and chemotherapy, exhibit a high recurrence rate. There is a need for new therapeutic approaches based on precision medicine informed by biomarker assessment and BRAF, a key regulator of MAPK signaling pathway, influencing cell differentiation, proliferation, migration and pro-tumorigenic activity, is emerging as a promising molecular target.

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Article Synopsis
  • Diffuse midline gliomas (DMG) and diffuse hemispheric gliomas (DHG) are rare tumors linked to specific histone alterations (H3K27 for DMG and H3G34 for DHG), with distinct clinical and molecular behaviors that necessitate personalized treatment approaches.
  • A comprehensive review of existing literature was conducted to assess current understanding of their clinical characteristics, radiological findings, and treatment options, including both loco-regional and systemic therapies.
  • Advances in understanding the genomic landscape of these tumors have identified promising new therapeutic targets, but most clinical trials currently focus on DMG, with limited options for DHG patients.
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Glioblastoma (GBM) is a malignant brain tumor exhibiting rapid and infiltrative growth, with less than 10% of patients surviving over 5 years, despite aggressive and multimodal treatments. The poor prognosis and the lack of effective pharmacological treatments are imputable to a remarkable histological and molecular heterogeneity of GBM, which has led, to date, to the failure of precision oncology and targeted therapies. Identification of molecular biomarkers is a paradigm for comprehensive and tailored treatments; nevertheless, biopsy sampling has proved to be invasive and limited.

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  • Current knowledge on anaplastic meningiomas includes insights into their diagnosis, genetics, and management strategies, emphasizing the need for trained specialists for accurate diagnosis.
  • While surgery and radiation therapy are primary treatments for these tumors, ongoing research into molecular pathways may eventually lead to new systemic therapies.
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The glioma-associated tumor microenvironment involves a multitude of different cells ranging from immune cells to endothelial, glial, and neuronal cells surrounding the primary tumor. The interactions between these cells and glioblastoma (GBM) have been deeply investigated while very little data are available on patients with lower-grade gliomas. In these tumors, it has been demonstrated that the composition of the microenvironment differs according to the isocitrate dehydrogenase status (mutated/wild type), the presence/absence of codeletion, and the expression of specific alterations including H3K27 and/or other gene mutations.

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