PROJECT SUMMARY Dyspnea is one of the most common and distressing symptoms associated with cancer, occurring in nearly 70% of patients with advanced cancer. Dyspnea is associated with impaired function, decreased quality of life, and shortened survival. Previous trials suggest that existing palliative interventions, such as low flow supplemental oxygen and opioids, have limited efficacy. Due to the paucity of high-quality evidence, there are currently no U.S. Food and Drug Administration (FDA)-approved treatment options. Multiple organizations, including the Institute of Medicine and National Hospice and Palliative Nurses Association, identified dyspnea as a priority for research. The long-term goal of our research is to develop evidence-based therapies for the palliation of dyspnea in patients with cancer. The overall objective of our proposed high risk, high impact, two-arm, parallel-group, wait- list control, randomized clinical trial is to compare the efficacy of a respiratory therapist (RT)-led Structured Personalized Oxygen and support Therapies for dyspnea in ONcology patients (SPOT-ON) intervention with enhanced usual care on dyspnea. Based on our preliminary data, we hypothesize that a personalized RT-led intervention incorporating time-limited trials of oxygen and support therapies would be effective in reducing dyspnea in acutely ill hospitalized patients with cancer. The two primary specific aims of this study are to compare the effect of SPOT-ON and enhanced usual care on the change in intensity of dyspnea at 24 h in hospitalized cancer patients with hypoxemia (Primary Aim 1) and without hypoxemia (Primary Aim 2). The third aim is to compare the effect of SPOT-ON and enhanced usual care on patient outcomes over 72 h, including dyspnea intensity, dyspnea unpleasantness, dyspnea response, vital signs, symptom burden, health-related quality of life, adverse events, pattern of device use, and hospital outcomes. The fourth aim is to assess factors associated with efficacy of the SPOT-ON intervention, including patient demographics, preferences, and level of usage of oxygen delivery modalities. After obtaining informed consent, a RT will administer the structured study interventions and monitor the participants closely for 72 hours. This study is highly innovative because (1) it will be the first clinical trial to specifically examine a RT-led intervention for palliation of dyspnea; (2) it will examine how time-limited trials can be used to personalize dyspnea management; (3) it will provide treatment based on patient preference instead of physician prescription; (4) it will test the effect of various oxygen modalities in patients without hypoxemia; (5) it adopts personalized dyspnea goal as a novel response criteria; and (6) it employs an innovative personalized trial design. Successful completion of this definitive study is expected to identify the optimal strategy to reduce dyspnea with oxygen- based and support therapies. Results of this study are expected to enhance quality of life for patients with advanced cancer, transform the management of dyspnea, and shift the paradigm of symptom research. .

PROJECT NARRATIVE The proposed research is relevant to public health because it will develop and evaluate a novel, personalized therapeutic approach for the management of dyspnea, one of the most common and distressing symptoms in hospitalized patients with cancer. In this patient-centered clinical study, we will take advantage of the acute nature of dyspnea to conduct a series of time-limited trials that will determine the optimal dyspnea treatment modalities for each patient. This research program is relevant to the mission of the National Institutes of Health because effective management of dyspnea will ultimately help to improve quality of life for patients suffering from this devastating symptom.