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In the case of our patient, the synergic action of endocrine therapy and chemotherapy plus dual anti-HER2 combination allowed a complete disease control. Therapy should be scheduled by considering the two cancers as individual entities. The approach to breast cancer is changing from being considered a singular disease to a multiform one, according to current research focused on biological markers such as HER2, ERs, and PRs, with important implications in clinical, prognostic, and therapeutic features. [ABSTRACT FROM AUTHOR]

This article describes a case of a glioneuronal tumor with ATRX alteration, kinase fusion, and anaplastic features (GTAKA) in an adolescent patient. The tumor initially presented as a supratentorial ependymoma but rapidly disseminated to the leptomeninges within three months of surgery. The tumor exhibited specific genetic and epigenetic features of GTAKA, including loss of ATRX expression, a ZMIZ1::RET fusion, and a DNA methylation signature consistent with GTAKA. The case adds to the limited literature on this rare group of tumors and highlights the need for further research on their biological behavior and treatment options. [Extracted from the article]

Diffuse midline glioma (DMG) is a heterogeneous group of aggressive pediatric brain tumors with a fatal prognosis. The biological hallmark in the major part of the cases is H3K27 alteration. Prognosis remains poor, with median survival ranging from 9 to 12 months from diagnosis. Clinical and radiological prognostic factors only partially change the progression-free survival but they do not improve the overall survival. Despite efforts, there is currently no curative therapy for DMG. Radiotherapy remains the standard treatment with only transitory benefits. No chemotherapeutic regimens were found to significantly improve the prognosis. In the new era of a deeper integration between histological and molecular findings, potential new approaches are currently under investigation. The entire international scientific community is trying to target DMG on different aspects. The therapeutic strategies involve targeting epigenetic alterations, such as methylation and acetylation status, as well as identifying new molecular pathways that regulate oncogenic proliferation; immunotherapy approaches too are an interesting point of research in the oncology field, and the possibility of driving the immune system against tumor cells has currently been evaluated in several clinical trials, with promising preliminary results. Moreover, thanks to nanotechnology amelioration, the development of innovative delivery approaches to overcross a hostile tumor microenvironment and an almost intact blood–brain barrier could potentially change tumor responses to different treatments. In this review, we provide a comprehensive overview of available and potential new treatments that are worldwide under investigation, with the intent that patient- and tumor-specific treatment could change the biological inauspicious history of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Embryonal tumors include a heterogeneous group of tumors that need multimodal and multidisciplinary treatments in which craniospinal irradiation (CSI) plays a major role, with a known impact on the acute toxicity and future quality of life of patients. Neutropenia represents one of the most common acute hematological side effects and is responsible for infections and treatment delays that can affect the effectiveness of therapy. To better describe hematological acute toxicity during proton beam radiation treatment, we retrospectively examined 20 subsequent pediatric patients affected by high-risk embryonal tumors subjected to CSI with dual-phase proton therapy after a chemotherapy regimen. Our data suggest that the dual-phase technique is safe and feasible in this setting of pediatric patients with a significant baseline hematological toxicity. Despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with proton therapy, and, therefore, no treatment was discontinued or delayed. Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed. [ABSTRACT FROM AUTHOR]