Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

Purpose Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC). Materials and methods This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1-5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT. Results Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4-91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5-19.1 months). One-and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8-25.8 months). One-year systemic treatment-free survival was 72.1%. Conclusion SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.

No abstract

No abstract

No abstract

In this review we summarize the currently available evidence about the role of hybrid machines for MR-guided radiotherapy for prostate stereotactic body radiotherapy. Given the novelty of this technology, to date few data are accessible, but they all report very promising results in terms of tolerability and preliminary clinical outcomes. Most of the studies highlight the favorable impact of on-board magnetic resonance imaging as a means to improve target and organs at risk identification with a consequent advantage in terms of dosimetric results, which is expected to relate to a more favorable toxicity pattern. Still, the longer treatment time per session may potentially affect the patient’s compliance to the treatment, although first quality of life assessment studies have reported substantial tolerability and no major impact on quality of life. Finally, in this review we hypothesize some future scenarios of further investigation, based on the possibility to explore the superior anatomy visualization and the role of daily adapted treatments provided by hybrid MR-Linacs.

No abstract

No abstract