Estimating survival in patients with melanoma brain metastases: prognostic value of lactate dehydrogenase.

Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P  < 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32 months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.

Integration of Cellular and Humoral Immune Responses as an Immunomonitoring Tool for SARS-CoV-2 Vaccination in Healthy and Fragile Subjects.

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients.

Optimizing CDK4/6 inhibitors in advanced HR+/HER2- breast cancer: A personalized approach.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy.

Management of breast cancer patients with chemotherapy-induced neutropenia or febrile neutropenia.

Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF.

Clinical advances in the development of novel VEGFR2 inhibitors.

Angiogenesis inhibitors have produced significant advances in the treatment of several tumors including colorectal, lung, ovarian and renal carcinomas. These agents, however, modestly impact on the overall cure rate, and their activity is often limited because of the early outbreak of redundant pathways or resistance mechanisms. Moreover, no clear predictive factor has been identified for treatment selection in the clinic. Preclinical evidence suggest that antibodies targeting the vascular endothelial growth factor (VEGF) axis may exert their activity throughout the inhibition of VEGF receptor 2 (VEGFR2) phosphorylation, a key factor in the cancer angiogenic process. Among other molecules, ramucirumab, an intravenously administered, fully humanized monoclonal antibody (mAb) targeting the extracellular domain of the receptor, and apatinib, a potent oral inhibitor of the intracellular domain, are emerging as original antiangiogenic opportunities. This up-to-date review focuses on the development of VEGFR2 inhibitors across multiple cancers and presents results of the most recent researches, ranging from early phase I studies to randomized phase III trials, in which those drugs have been tested as a single-agent or in combination with different chemotherapy regimens.

Feasibility study of a web application for self-report of anticancer treatment toxicities.

Collection of collateral effects related to toxicities suffered by patients being exposed to anticancer treatments is of crucial importance in clinical practice but also in oncological research. The present paper describes a web application called PaTOS for self-report of anticancer therapy toxicities, and its evaluation in a preliminary interface analysis and then in a feasibility study.