Therapeutic inhibition of isocitrate dehydrogenase mutations in glioma and cholangiocarcinoma: new insights and promises-a narrative review.

Background And Objective: The identification of mutation hot spots in the isocitrate dehydrogenase (IDH) genes is one of the most important cancer genome-wide sequencing discoveries with relevant impact in the treatment of some orphan tumors. These genes were mostly found mutated in lower-grade gliomas (LGGs), acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and in cholangiocarcinoma. This aberrant genomic condition represents a therapeutic target of great interest in cancer research, especially in AML, given the limitations of currently approved therapies in this field.

REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma.

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 glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function.

Present and Future of Immunotherapy in Patients With Glioblastoma: Limitations and Opportunities.

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 approaches, considering the success in other solid tumors.

Mucosal Melanoma: Epidemiology, Clinical Features, and Treatment.

Purpose Of Review: Summarize the writings published in the last years on the management and novel therapies of mucosal melanoma (MM).

Recent Findings: New research has demonstrated a difference between MM and cutaneous melanoma (CM) in their genomic and molecular landscapes, explaining the response's heterogeneity. Immunotherapy and targeted therapy have limited benefit, but novel therapies are rapidly expanding.

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

Background: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC).

Patients And Methods: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled.

Melanoma Brain Metastases: A Retrospective Analysis of Prognostic Factors and Efficacy of Multimodal Therapies.

Brain metastasis in cutaneous melanoma (CM) has historically been considered to be a dismal prognostic feature, although recent evidence has highlighted the intracranial activity of combined immunotherapy (IT). Herein, we completed a retrospective study to investigate the impact of clinical-pathological features and multimodal therapies on the overall survival (OS) of CM patients with brain metastases. A total of 105 patients were evaluated.

The Analysis of Trends in Survival for Patients with Melanoma Brain Metastases with Introduction of Novel Therapeutic Options before the Era of Combined Immunotherapy-Multicenter Italian-Polish Report.

Stage IV melanoma patients develop melanoma brain metastases (MBM) in 50% of cases. Their prognosis is improving, and its understanding outside the context of clinical trials is relevant. We have retrospectively analyzed the clinical data, course of treatment, and outcomes of 531 subsequent stage IV melanoma patients with BM treated in five reference Italian and Polish melanoma centers between 2014 and 2021.

Observational real-life study on regorafenib in recurrent glioblastoma: does dose reduction reduce toxicity while maintaining the efficacy?

Purpose: In the phase 2 REGOMA trial, regorafenib improved overall survival, as compared with lomustine, in glioblastoma (GBM) patients at first progression after chemoradiation. Recently, some real-life trials showed similar impact on survival but a higher rate of adverse events than in REGOMA, thus raising concerns over tolerability. The aim of this study was to assess the efficacy and tolerability of a lower intensity regorafenib regimen.

Newly diagnosed Glioblastoma Multiforme (GBM) during COVID-19 pandemic: changes in therapeutic approach to minimize in-hospital SARS-COV-2 contagion in pre-vaccine era.

COVID-19 pandemic revolutionized the way in which cancer patients are treated worldwide. Regarding neuro-oncological patients, usually considered frail and with lower life-expectancy in respect to other oncological patients, the international scientific community had to urgently reorganize the treatment approach in order to minimize the risk of in-hospital contagious. For GBM patients, adjuvant treatments have been evaluated with even much more attention with regard to the expected efficacy.

Molecular Aberrations Stratify Grade 2 Astrocytomas Into Several Rare Entities: Prognostic and Therapeutic Implications.

The identification of specific molecular aberrations guides the prognostic stratification and management of grade 2 astrocytomas. Mutations in isocitrate dehydrogenase () 1 and 2, found in the majority of adult diffuse low-grade glioma (DLGG), seem to relate to a favorable prognosis compared to wild-type (-wt) counterparts. Moreover, the -wt group can develop additional molecular alterations worsening the prognosis, such as epidermal growth factor receptor amplification (amp) and mutation of the promoter of telomerase reverse transcriptase ().

Papillary Meningioma: Case Presentation with Emphasis on Surgical and Medical Therapy of a Rare Variant of Meningioma.

Meningioma is one of the most frequent neoplasms of all in the central nervous system. Different variants are known, and of these some have peculiar characteristics, both from a morphological point of view and from a biological point of view. Here, we present a rare case of relapsed papillary meningioma in a young patient, focusing on histological characteristics, medical-surgical therapy and focusing on the risk of progression and/or recurrence of the lesion if not completely eradicated.

The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice.

Molecular alterations of the Ataxia-telangiectasia () gene are frequently detected in breast cancer (BC), with an incidence ranging up to 40%. The mutated form, the Ataxia-telangiectasia mutated () gene, is involved in cell cycle control, apoptosis, oxidative stress, and telomere maintenance, and its role as a risk factor for cancer development is well established. Recent studies have confirmed that some variants of are associated with an increased risk of BC development and a worse prognosis.

Prognostic Factors and Current Treatment Strategies for Renal Cell Carcinoma Metastatic to the Brain: An Overview.

Renal cell carcinoma (RCC) is one of primary cancers that frequently metastasize to the brain. Brain metastasis derived from RCC has the propensity of intratumoral hemorrhage and relatively massive surrounding edema. Moreover, it confers a grim prognosis in a great percentage of cases with a median overall survical (mOS) around 10 months.

Management of Brain and Leptomeningeal Metastases from Breast Cancer.

The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians.

Liquid Biopsy as a Tool Exploring in Real-Time Both Genomic Perturbation and Resistance to EGFR Antagonists in Colorectal Cancer.

The treatment of metastatic colorectal cancer (mCRC) has improved since the introduction of the epithelial growth factor receptor (EGFR) inhibitors as cetuximab and panitumumab. However, only patients with peculiar genomic profiles benefit from these targeting therapies. In fact, the molecular integrity of genes is a predominant factor conditioning both primary and acquired resistance in non-responders although additional molecular derangements induced by selective anti-EGFR pressure may concur to the failure of those disease treatment, liquid biopsy (LB) appears as a surrogate of tissue biopsy, provides the genomic information to reveal tumor resistance to anti-EGFR agents, the detection of minimal residual disease before adjuvant therapies, and the discovery of tumor molecular status suitable for rechallenging treatments with EGFR antagonists.

Current clinical management of elderly patients with glioma.

Introduction: The incidence of gliomas is increasing in elderly patients. Clinical factors, such as age, performance status, and comorbidities contribute when choosing adequate treatment in older patients.

Areas Covered: This review covers the main pathological and molecular features of gliomas in elderly patients, as well as the neurological and geriatric assessment to select patients for surgery and antineoplastic treatments.

Pulmonary enteric adenocarcinoma: an overview.

Most commonly described as sporadic, pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare variant of invasive lung cancer recently established and recognised by the World Health Organization. This tumour is highly heterogeneous and shares several morphological features with pulmonary and colorectal adenocarcinomas. Our objective is to summarise current research on PAED, focusing on its immunohistochemical and molecular features as potential tools for differential diagnosis from colorectal cancer, as well as prognosis definition and therapeutic choice.

Cutaneous metastasis as a primary presentation of a pulmonary enteric adenocarcinoma.

Background: Primary pulmonary enteric adenocarcinoma (PEAC) is a rare non-small cell lung cancer subtype sharing morphologic and immunohistochemical features with colorectal adenocarcinoma. Given the frequency of lung metastases in colorectal cancer, the differential diagnosis of PEAC according to routine morphological and immunohistochemical findings may be difficult. Genome sequence by next-generation sequencing has recently introduced new perspectives to better define the diagnosis and tumor sensitivity to treatments, while the rarity of this subtype of cancer still limits the current knowledge of its molecular features and provides no information to address patients to tailored therapies.