Glioblastoma (GBM) is the most common primary adult brain malignancy with an extremely poor prognosis and a median survival of fewer than two years. A key reason for this high mortality is that the blood–brain barrier (BBB) significantly restricts systemically delivered therapeutics to brain tumors. High-intensity focused ultrasound (HIFU) with microbubbles is a methodology being used in clinical trials to noninvasively permeabilize the BBB for systemic therapeutic delivery to GBM. Topotecan is a topoisomerase inhibitor used as a chemotherapeutic agent to treat ovarian and small cell lung cancer. Studies have suggested that topotecan can cross the BBB and can be used to treat brain metastases. However, pharmacokinetic data demonstrated that topotecan peak concentration in the brain extracellular fluid after systemic injection was ten times lower than in the blood, suggesting less than optimal BBB penetration by topotecan. We hypothesize that HIFU with microbubbles treatment can open the BBB and significantly increase topotecan concentration in the brain. We radiolabeled topotecan with ¹¹C and acquired static and dynamic positron emission tomography (PET) scans to quantify [¹¹C] topotecan uptake in the brains of normal mice and mice after HIFU treatment. We found that HIFU treatments significantly increased [¹¹C] topotecan brain uptake. Moreover, kinetic analysis of the [¹¹C] topotecan dynamic PET data demonstrated a substantial increase in [¹¹C] topotecan volume of distribution in the brain. Furthermore, we found a decrease in [¹¹C] topotecan brain clearance, confirming the potential of HIFU to aid in the delivery of topotecan through the BBB. This opens the potential clinical application of [¹¹C] topotecan as a tool to predict topotecan loco-regional brain concentration in patients with GBMs undergoing experimental HIFU treatments.

Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy.

The purpose of this paper is to describe the Automated Heart-Health Assessment (AH-HA) study protocol, which demonstrates an agile approach to cancer care delivery research. This study aims to assess the effect of a clinical decision support tool for cancer survivors on cardiovascular health (CVH) discussions, referrals, completed visits with primary care providers and cardiologists, and control of modifiable CVH factors and behaviors. The COVID-19 pandemic has caused widespread disruption to clinical trial accrual and operations. Studies conducted with potentially vulnerable populations, including cancer survivors, must shift towards virtual consent, data collection, and study visits to reduce risk for participants and study staff. Studies examining cancer care delivery innovations may also need to accommodate the increased use of virtual visits. This group-randomized, mixed methods study will recruit 600 cancer survivors from 12 National Cancer Institute Community Oncology Research Program (NCORP) practices. Survivors at intervention sites will use the AH-HA tool with their oncology provider; survivors at usual care sites will complete routine survivorship visits. Outcomes will be measured immediately after the study visit, with follow-up at 6 and 12 months. The study was amended during the COVID-19 pandemic to allow for virtual consent, data collection, and intervention options, with the goal of minimizing participant-staff in-person contact and accommodating virtual survivorship visits. Changes to the study protocol and procedures allow important cancer care delivery research to continue safely during the COVID-19 pandemic and give sites and survivors flexibility to conduct study activities in-person or remotely.