The care cascade following a supportive management intervention for patients presenting to a radiation oncology clinic.

Patients with cancer have many psychosocial needs, some of which may be addressed by implementation of a screening tool. However, it is unknown what ultimately happens (i.e., the "care cascade") to patients following these interventions. The objective of this study was to evaluate the care cascade for patients following the implementation of a psychosocial needs screening tool. This was a prospective cohort study conducted at a university hospital radiation oncology clinic. Participants who were 18 years or older and presenting for their initial radiation oncology appointment were asked to complete a screening survey. From December 2019 to January 2021, 242 patients completed the survey. 70% of patients were seen for consideration of definitive therapy. 62% of patients checked "yes" to at least one item, most commonly supportive/palliative care (33%), exercise/PT (26%) and advance care planning (26%). Among definitive patients, the most common were supportive/palliative care (33%) and exercise/PT (26%). Among palliative patients, the most common were supportive/palliative care (42%) and advance care planning (32%). Participants were followed for 6 months after taking the survey. 74% of patients with a positive screening survey were contacted by a social worker and/or had a new referral placed with 47% of those patients ultimately attending a new appointment. Screening tools are commonly implemented to quickly identify needs in oncology patients. This study tracked patients following this type of intervention to determine what proportion of patients ultimately received care related to the identified need. Despite the majority of patients being referred to a relevant provider, fewer than half ultimately attended appointments. The combination of a screening tool with social work triage may be an effective way to distribute resources and properly route patients to supportive care providers.

Acute myeloid leukemia-induced T-cell suppression can be reversed by inhibition of the MAPK pathway.

Acute myeloid leukemia (AML) remains difficult to treat due to mutational heterogeneity and the development of resistance to therapy. Targeted agents, such as MEK inhibitors, may be incorporated into treatment; however, the impact of MEK inhibitors on the immune microenvironment in AML is not well understood. A greater understanding of the implications of MEK inhibition on immune responses may lead to a greater understanding of immune evasion and more rational combinations with immunotherapies. This study describes the impact of trametinib on both T cells and AML blast cells by using an immunosuppressive mouse model of AML and primary patient samples. We also used a large AML database of functional drug screens to understand characteristics of trametinib-sensitive samples. In the mouse model, trametinib increased T-cell viability and restored T-cell proliferation. Importantly, we report greater proliferation in the CD8+CD44+ effector subpopulation and impaired activation of CD8+CD62L+ naive cells. Transcriptome analysis revealed that trametinib-sensitive samples have an inflammatory gene expression profile, and we also observed increased programmed cell death ligand 1 (PD-L1) expression on trametinib-sensitive samples. Finally, we found that trametinib consistently reduced PD-L1 and PD-L2 expression in a dose-dependent manner on the myeloid population. Altogether, our data present greater insight into the impact of trametinib on the immune microenvironment and characteristics of trametinib-sensitive patient samples.