Intrathecal topotecan with systemic checkpoint inhibitor therapy for gastroesophageal cancer with leptomeningeal involvement: two case reports and review of the literature.

Background: Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments. Case Description: Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed. Conclusions: We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.

End-of-Life Care and Advanced Directives in Hispanic/Latinx Patients: Challenges and Solutions for the Practicing Oncologist.

Advanced end-of-life care (EOL) comprises a group of strategies to provide comfort to patients at the end of life. These are associated with better quality of life, better satisfaction, and a lower rate of hospitalizations and aggressive medical treatment. Advanced EOL care, including advanced directives completion and hospice enrollment, is suboptimal among Hispanic/Latinx patients with cancer due to personal, socio-cultural, financial, and health system-related barriers, as well as due to a lack of studies specifically designed for this population. In addition, the extrapolation of programs that increase participation in EOL for non-white Hispanics may not work appropriately for Hispanic/Latinx patients and lead to overall lower satisfaction and enrollment in EOL care. This review will provide the practicing oncologist with the tools to address EOL in the Hispanic/Latinx population. Some promising strategies to address the EOL care disparities in Latinx/Hispanic patients have been culturally tailored patient navigation programs, geriatric assessment-guided multidisciplinary interventions, counseling sessions, and educational interventions. Through these strategies, we encourage oncologists to take advantage of every clinical setting to discuss EOL care. Treating physicians can engage family members in caring for their loved ones while practicing cultural humility and respecting cultural preferences, incorporating policies to foster treatment for the underserved migrant population, and providing patients with validated Spanish language tools.

Acute myeloid leukemia: therapeutic targeting of stem cells.

INTRODUCTION: Despite advances in the treatment of acute myeloid leukemia (AML), long-term survival remains low. In 1994, it was proposed that leukemic stem cells (LSCs) played a key role in relapsed and refractory disease. LSCs are capable of self-renewal, proliferation, differentiation, immune evasion, and drug resistance through several unique mechanisms. More recent leukemia drug development initiatives have included efforts to target LSCs. With LSCs, the challenge with such drug design is finding a way to selectively target LSCs while sparing normal hematopoietic stem cells (HSCs). AREAS COVERED: In this review, we explore the evolving knowledge of the unique LSC biology and physiology in the scientific literature, while noting the several agents that have been designed throughout the years to target this subgroup of leukemic cells. Our review includes discussion on chimeric antigen receptor T cells, monoclonal antibodies, antibody-drug conjugates against cell surface markers, signaling pathway targets, pro-apoptotic agents, epigenetic regulators, and more. EXPERT OPINION: As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.