Association of a Lay Health Worker-Led Intervention on Goals of Care, Quality of Life, and Clinical Trial Participation Among Low-Income and Minority Adults With Cancer.

PURPOSE: New approaches are needed to overcome low supportive care and clinical trial participation among low-income and minority adults with cancer. The objective of this project was to determine whether a lay health worker intervention was associated with improvements in supportive care and trial participation. METHODS: We conducted a quality improvement initiative in collaboration with a union organization. We enrolled union members newly diagnosed with cancer into a 6-month lay health worker-led intervention from October 15, 2016, to February 28, 2017. The primary outcome was goals of care. Secondary outcomes were health-related quality of life (HRQOL), health care use, and trial participation. All outcomes except HRQOL were compared with a cohort of union members diagnosed within the 6-month preintervention period. RESULTS: Sixty-six adults participated in the intervention group, and we identified 72 adults in the control group. Demographic characteristics were similar between groups. The mean age was 56.0 years; 47 (34%) were male, and 22 were White (16%). Within 6 months enrollment, more intervention group participants, as compared with the control, had clinician-documented goals of care (94% v 26%; P < .001) and participated in cancer clinical trials (72% v 22%; P < .001). At 4 months postenrollment, as compared with baseline, intervention participants experienced HRQOL improvements (mean difference, 3.98 points; standard deviation, 2.83; P < .001). Before death, more intervention group participants used palliative care and hospice than the control group. CONCLUSION: Lay health worker-led interventions may improve supportive care and clinical trial participation among low-income and minority populations with cancer.

Lay Health Workers' Perspectives on Delivery of Advance Care Planning and Symptom Screening Among Adults With Cancer: A Qualitative Study.

INTRODUCTION: Advance care planning and symptom screening among patients with cancer require team-based approaches to ensure that these services are equitably and appropriately delivered. In several organizations across the United States, we trained and employed lay health workers (LHWs) to assist with delivering these services for patients with cancer. The aim of this study was to understand LHWs' views on delivering these services. METHODS: We conducted semi-structured interviews with 22 LHWs in 6 US-based clinical cancer care settings in 4 large cities. We recorded, transcribed, and analyzed interviews using the constant comparative method of qualitative analysis. RESULTS: Participants noted the importance of their role in assisting with the delivery of advance care planning (ACP) and symptom screening services. Participants noted the importance of developing relationships with patients to engage openly in ACP and symptom screening discussions. Participants reported that ongoing training provided skills and empowered them to discuss sensitive issues with patients and their caregivers. Participants described challenges in their roles including communication with oncology providers and their own emotional well-being. Participants identified solutions to these challenges including formal opportunities for introduction with oncology clinicians and staff and grievance sessions with LHWs and other team members. DISCUSSION: LHWs from several organizations endorsed the importance of their roles in ensuring the delivery of ACP and proactive symptom screening. LHWs noted challenges and specific solutions to improve their effectiveness in delivering these important services to patients after their diagnosis of cancer.

A randomized trial of a multi-level intervention to improve advance care planning and symptom management among low-income and minority employees diagnosed with cancer in outpatient community settings.

INTRODUCTION: Equitable delivery of advance care planning and symptom management among patients is crucial to improving cancer care. Existing interventions to improve the uptake of these services have predominantly occurred in clinic settings and are limited in their effectiveness, particularly among low-income and minority populations. METHODS: The "Lay health worker Educates Engages and Activates Patients to Share (LEAPS)" intervention was developed to improve advance care planning and symptom management among low-income and minority hourly-wage workers with cancer, in two community settings. The intervention provides a lay health worker to all patients newly diagnosed with cancer and aims to educate and activate patients to engage in advance care planning and symptom management with their oncology providers. In this randomized clinical trial, we will evaluate the effect on quality of life (primary outcome) using the validated Functional Assessment of Cancer Therapy - General Survey, at enrollment, 4- and 12- months post-enrollment. We will examine between-group differences on our secondary outcomes of patient activation, patient satisfaction with healthcare decision-making, and symptom burden (at enrollment, 4- and 12-months post-enrollment), and total healthcare use and healthcare costs (at 12-months post-enrollment). DISCUSSION: Multilevel approaches are urgently needed to improve cancer care delivery among low-income and minority patients diagnosed with cancer in community settings. The current study describes the LEAPS intervention, the study design, and baseline characteristics of the community centers participating in the study. ClinicalTrials.gov Registration #NCT03699748.

Targeting Mitochondrial Proline Dehydrogenase with a Suicide Inhibitor to Exploit Synthetic Lethal Interactions with p53 Upregulation and Glutaminase Inhibition.

Proline dehydrogenase (PRODH) is a p53-inducible inner mitochondrial membrane flavoprotein linked to electron transport for anaplerotic glutamate and ATP production, most critical for cancer cell survival under microenvironmental stress conditions. Proposing that PRODH is a unique mitochondrial cancer target, we structurally model and compare its cancer cell activity and consequences upon exposure to either a reversible (S-5-oxo: S-5-oxo-2-tetrahydrofurancarboxylic acid) or irreversible (N-PPG: N-propargylglycine) PRODH inhibitor. Unlike 5-oxo, the suicide inhibitor N-PPG induces early and selective decay of PRODH protein without triggering mitochondrial destruction, consistent with N-PPG activation of the mitochondrial unfolded protein response. Fly and breast tumor (MCF7)-xenografted mouse studies indicate that N-PPG doses sufficient to phenocopy PRODH knockout and induce its decay can be safely and effectively administered in vivo Among breast cancer cell lines and tumor samples, PRODH mRNA expression is subtype dependent and inversely correlated with glutaminase (GLS1) expression; combining inhibitors of PRODH (S-5-oxo and N-PPG) and GLS1 (CB-839) produces additive if not synergistic loss of cancer cell (ZR-75-1, MCF7, DU4475, and BT474) growth and viability. Although PRODH knockdown alone can induce cancer cell apoptosis, the anticancer potential of either reversible or irreversible PRODH inhibitors is strongly enhanced when p53 is simultaneously upregulated by an MDM2 antagonist (MI-63 and nutlin-3). However, maximum anticancer synergy is observed in vitro when the PRODH suicide inhibitor, N-PPG, is combined with both GLS1-inhibiting and a p53-upregulating MDM2 antagonist. These findings provide preclinical rationale for the development of N-PPG-like PRODH inhibitors as cancer therapeutics to exploit synthetic lethal interactions with p53 upregulation and GLS1 inhibition.