Effectiveness of Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) in the uterine adenomyosis treatment: technical approach and MRI evaluation.

PURPOSE: To evaluate the treatment efficacy of uterine adenomyosis using MRgFUS as a mini-invasive therapy. MATERIALS AND METHODS: Twenty-three patients affected by symptomatic uterine adenomyosis (11 focal and 7 diffuse forms), diagnosed using MRI, were included in this study. Eighteen out of 23 were submitted to MRgFUS. All junctional zone more than 12 mm in width were considered to be adenomyosis. Study evaluates the pre-treatment target volume measured prior to the treatment on the CE T1-weighted sequence and the MRgFUS-treated volume (MRgFUS-TV), represented by the volume of the lesion ablated, measured directly by means of the MRgFUS. The treated volume on the CE T1-weighted sequence (CE MRI-TV) was measured immediately after treatment. After 1 year, the junctional zone thickness was measured in order to compare pre- and post-treatment values. The therapeutic plan consisted of a high-energy-grid sonication. Symptomatology was assessed through the UFS-QOL. RESULTS: The pre-treatment target volume mean value was of 59.7 cc; the MRgFUS-TV had a mean value of 44.9 cc, and the mean value of CE MRI-TV, measured immediately after treatment, was of 52.8 cc, with an increase of 13.7%. The 86.5% of the lesion was treated. After 1 year from the treatment, 15/18 (83%) patients showed thickness of the junctional zone <12 mm; 3/18 (17%) had a junctional zone >12 mm. CONCLUSION: MRgFUS is an encouraging mini-invasive treatment for adenomyosis that permits to maintain the integrity of the uterus in a pathology with limited therapeutic possibility.

Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated.