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Benefits of stereotactic radiosurgery (SRS) have been well established in melanoma brain metastases (MBM). Immunotherapy agents such as ipilimumab (ipi) have recently demonstrated clinical efficacy in advanced disease as well. The theoretical synergistic effects of combining these therapies in MBM have not been explored in detail, however, we conducted a systematic review with meta-analysis of studies that compared combined SRS and ipi versus SRS alone in MBM. Medical Literature Analysis and Retrieval System Online (MEDLINE) and Central databases were used for our literature search, which was conducted by three reviewers. We included studies that examined SRS and ipilimumab compared to SRS alone in MBM. Pertinent results were tabulated in a standardized spreadsheet. Newcastle-Ottawa Scale (NOS) Risk of Bias Assessment and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method for rating evidence quality were used for qualitative analysis. Review Manager was used for statistical analysis. We identified four cohort studies that compared SRS plus ipi versus SRS alone in MBM. As per the GRADE criteria, we found low-quality evidence for survival benefits associated with combined treatment. Meta-analysis confirmed a significant benefit in survival for SRS and ipilimumab (hazard ratio 0.38, 95% confidence interval 0.28 - 0.52, p < 0.01). There were no significant differences between comparison groups for local control, distant brain control, radiation necrosis, or intracranial bleeding. We conclude that low-quality evidence exists for superior overall survival in MBM treated with SRS and ipilimumab compared to SRS without ipilimumab. There is also no increased risk of radiation necrosis and/or intracranial bleeding with combining radiation and immunotherapy in this setting.

Metastatic triple-negative breast cancer (TNBC) constitutes a heterogeneous group of diseases with systemic treatment options limited to cytotoxic chemotherapy at the time being. The disease tends to affect visceral organs more frequently when compared to hormone receptor-positive breast cancer. The prognoses of patients with heavily pretreated disease affecting the liver are very dismal. We present the response to radioembolization and systemic chemotherapy in a seriously ill patient who had undergone previous lines of chemotherapy for TNBC with extensive liver metastases.

Objective: To evaluate the effectiveness and tolerability of neoadjuvant chemotherapy with weekly paclitaxel in combination with weekly carboplatin area under curve 2 followed by anthracycline chemotherapy. Patients and methods: This is a retrospective review of electronic medical records of patients (N = 32) with stage 1c–III triple-negative breast cancer. Patients received neoadjuvant chemotherapy with paclitaxel 80 mg/m2 once per week for 12 weeks in combination with carboplatin area under curve 2 once per week for 12 weeks (wP + wCb), followed by a standard anthracycline regimen including either doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 or 3 weeks, or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for four cycles with myeloid growth factor support. Results: Most patients (91%) received all 12 cycles of wP + wCb, and 88% received all four planned cycles of anthracycline chemotherapy. Of the patients, 84% completed all planned therapies. The complete pathologic response rate was 60%. In terms of hematologic toxicity, 96% of the patients experienced grade ≥3 leucopenia, 40% grade ≥3 anemia, and 15% grade ≥3 thrombocytopenia, and neutropenic fever was seen in 22% of the patients. Conclusion: The combination of neoadjuvant chemotherapy with wP + wCb before anthracycline chemotherapy can be tolerated by patients with triple-negative breast cancer. Complete pathologic response rates were comparable with those historically seen. Careful selection of patients is fundamental as this regimen is associated with a high incidence of hematologic toxicity. Keywords: Triple negative breast cancer, Neoadjuvant chemotherapy

Endocrine therapy (ET) is the usual first-line therapy for patients with hormone receptor-positive metastatic breast cancer (HR+MBC). However, resistance to ET frequently occurs during the course of treatment. Cellular pathways involved in cell proliferation are targets for new drugs that interfere with development of resistance to ET. Cyclin-dependent kinases (CDKs) are a subgroup of serine/ threonine kinases that play a key role in regulating cell cycle progression. In this review, we discuss the currently approved and under investigation CDK 4/6 inhibitors, in addition to their preclinical data and clinical trials that demonstrated their benefit in the treatment of HR+ breast cancer.

The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process. Despite the promise of this strategy, clinical trials of preexposure prophylaxis have had limited degrees of success in humans, in part because of lack of adherence to the recommended preexposure treatment regimens. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza and human papilloma virus. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans.