Predictive value of perilesional edema volume in melanoma brain metastasis response to stereotactic radiosurgery.

Background And Aim: Stereotactic radiotherapy (SRT) is an established treatment for melanoma brain metastases (MBM). Recent evidence suggests that perilesional edema volume (PEV) might compromise the delivery and efficacy of radiotherapy to treat BM. This study investigated the association between SRT efficacy and PEV extent in MBM.

Correction: Gravina et al. ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma. 2022, , 289.

In the original publication [...

HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks.

Radiotherapy (RT) plays a critical role in the management of rhabdomyosarcoma (RMS), the prevalent soft tissue sarcoma in childhood. The high risk PAX3-FOXO1 fusion-positive subtype (FP-RMS) is often resistant to RT. We have recently demonstrated that inhibition of class-I histone deacetylases (HDACs) radiosensitizes FP-RMS both in vitro and in vivo.

Antitumour effects of SFX-01 molecule in combination with ionizing radiation in preclinical and in vivo models of rhabdomyosarcoma.

Background: Despite a multimodal approach including surgery, chemo- and radiotherapy, the 5-year event-free survival rate for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in childhood, remains very poor for metastatic patients, mainly due to the selection and proliferation of tumour cells driving resistance mechanisms. Personalised medicine-based protocols using new drugs or targeted therapies in combination with conventional treatments have the potential to enhance the therapeutic effects, while minimizing damage to healthy tissues in a wide range of human malignancies, with several clinical trials being started. In this study, we analysed, for the first time, the antitumour activity of SFX-01, a complex of synthetic d, l-sulforaphane stabilised in alpha-cyclodextrin (Evgen Pharma plc, UK), used as single agent and in combination with irradiation, in four preclinical models of alveolar and embryonal RMS.

Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

Background: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas.

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence.

The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph-ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation.

Abscopal Effect on Bone Metastases from Solid Tumors: A Systematic Review and Retrospective Analysis of Challenge within a Challenge.

Background: Abscopal effect (AE) describes the ability of radiotherapy (RT) to induce immune-mediated responses in nonirradiated distant metastasis. Bone represents the third most frequent site of metastasis and an immunologically favorable environment for the proliferation of cancer cells. We revised the literature, searching documented cases of AE involving bone metastases (BMs) and evaluated the incidence of AE involving BMs in patients requiring palliative RT on BMs or non-BMs treated at our department.

The botanical drug PBI-05204, a supercritical CO extract of , sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy and .

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na/K-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties.

Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models.

Background: Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. Current standard of care treatments have very limited efficacy, being the patients´ overall survival 14 months and the 2-year survival rate less than 10%. Therefore, the treatment of GBM is an urgent unmet clinical need.

Hypofractionated Radiotherapy in Intermediate-Risk Prostate Cancer Patients: Long-Term Results.

Background: To evaluate outcomes in terms of survival and toxicity in a series of intermediate-risk prostate cancer (PCa) patients treated with hypofractionated radiotherapy (HyRT) + hormonal therapy (HT) with or without image guidance (IGRT) and to investigate the impact of different variables. Methods: This is a multi-centric study. From January 2005 to December 2019, we treated 313 intermediate-risk PCa patients (T2b−T2c, Gleason score 7, or pre-treatment PSA 10 to 20 ng/mL) with HyRT.

The Botanical Drug PBI-05204, a Supercritical CO Extract of Nerium Oleander, Is Synergistic With Radiotherapy in Models of Human Glioblastoma.

Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from , as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties.

ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma.

Cell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs).

CT-guided cryoablation for management of bone metastases: a single center experience and review of the literature.

Thermal ablation techniques are procedures of growing interest for management of bone metastases. Among these, cryoablation is probably the most advanced. It allows treatment of large and irregular volumes of pathological tissue, real-time evaluation of the area of ablation and appears less painful than heat-based ablative techniques like radiofrequency and microwaves.

The impact of the incorporation of a feasible postoperative mortality model at the Post-Anaesthestic Care Unit (PACU) on postoperative clinical deterioration: A pragmatic trial with 5,353 patients.

Background: Practical use of risk predictive tools and the assessment of their impact on outcome reduction is still a challenge. This pragmatic study of quality improvement (QI) describes the preoperative adoption of a customised postoperative death probability model (SAMPE model) and the evaluation of the impact of a Postoperative Anaesthetic Care Unit (PACU) pathway on the clinical deterioration of high-risk surgical patients.

Methods: A prospective cohort of 2,533 surgical patients compared with 2,820 historical controls after the adoption of a quality improvement (QI) intervention.

MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant.

Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

Aim: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients.

Romidepsin (FK228) fails in counteracting the transformed phenotype of rhabdomyosarcoma cells but efficiently radiosensitizes, in vitro and in vivo, the alveolar phenotype subtype.

Purpose: Herein we describe the in vitro and in vivo activity of FK228 (Romidepsin), an inhibitor of class I HDACs, in counteracting and radiosensitizing embryonal (ERMS, fusion-negative) and alveolar (ARMS, fusion-positive) rhabdomyosarcoma (RMS).

Methods: RH30 (ARMS, fusion-positive) and RD (ERMS, fusion-negative) cell lines and human multipotent mesenchymal stromal cells (HMSC) were used. Flow cytometry analysis, RT-qPCR, western blotting and enzymatic assays were performed.

Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms.

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms.

Recommendation for the contouring of limbic system in patients receiving radiation treatment: A pictorial review for the everyday practice and education.

Aims: The limbic circuit (LC) is devoted to linking emotion to behavior and cognition. The injury this system results in post-RT cognitive dysfunction. The aim of this study is to create the first radiation oncologist's practical MR-based contouring guide for the delineation of the LC for the everyday clinical practice and education.

Apparent diffusion coefficient magnetic resonance imaging (ADC-MRI) in the axillary breast cancer lymph node metastasis detection: a narrative review.

The presence of axillary lymph nodes metastases in breast cancer is the most significant prognostic factor, with a great impact on morbidity, disease-related survival and management of oncological therapies; for this reason, adequate imaging evaluation is strictly necessary. Physical examination is not enough sensitive to assess breast cancer nodal status; axillary ultrasonography (US) is commonly used to detect suspected or occult nodal metastasis, providing exclusively morphological evaluation, with low sensitivity and positive predictive value. Currently, sentinel lymph node biopsy (SLNB) and/or axillary dissection are the milestone for the diagnostic assessment of axillary lymph node metastases, although its related morbidity.