Nonpharmacological Interventions for Managing Breathlessness in Patients With Advanced Cancer A Systematic Review

This systematic review reports the outcomes and evidence in randomized clinical trials of nonpharmacological treatment options for alleviating breathlessness and their implications for clinical guidelines and practice in advanced cancer. Question What are the advantages and harms of nonpharmacological interventions for managing breathlessness in adults with advanced cancer? Findings In this systematic review of 29 randomized clinical trials of breathlessness in 2423 adults with advanced cancer, several interventions such as fan therapy, noninvasive positive pressure ventilation, integrative medicine techniques (acupressure or reflexology), and multicomponent interventions (combined activity and rehabilitation, behavioral and psychoeducational, and integrative medicine) were associated with improved breathlessness compared with usual care or control interventions. Adverse events and related dropouts were uncommon. Meaning This systematic review found that nonpharmacological interventions were associated with improved breathlessness and uncommon adverse events, suggesting that these treatments should be considered as first-line options in patients with advanced cancer. Importance Breathlessness is a frequent and debilitating symptom in patients with advanced cancer. Often, in the context of breathlessness, aggressive cancer treatment is not beneficial, feasible, or aligned with goals of care. Targeted symptom-focused interventions may be helpful in this scenario. Objective To evaluate the advantages and harms of nonpharmacological interventions for managing breathlessness in adults with advanced cancer. Evidence Review PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception through May 2020 for published randomized clinical trials (RCTs), nonrandomized controlled trials, and observational studies of the advantages and/or harms of nonpharmacological interventions on alleviating breathlessness in adults with advanced cancer. Only English-language studies were screened for eligibility, titles, abstracts, and full text. Risk of bias and strength of evidence (SOE) were independently assessed. The key outcomes reported in studies were breathlessness, anxiety, exercise capacity, health-related quality of life, and harms. Data were analyzed from October 1, 2019, to June 30, 2020. Findings A total of 29 RCTs (2423 participants) were included. These RCTs evaluated various types of interventions, such as respiratory (9 RCTs), activity and rehabilitation (7 RCTs), behavioral and psychoeducational (3 RCTs), integrative medicine (4 RCTs), and multicomponent (6 RCTs). Several nonpharmacological interventions were associated with improved breathlessness, including fan therapy (standardized mean difference [SMD], -2.09; 95% CI, -3.81 to -0.37; I-2 = 94.3%; P for heterogeneity = .02; moderate SOE) and bilevel ventilation (estimated slope difference, -0.58; 95% CI, -0.92 to -0.23; low SOE), lasting for a few minutes to hours, in the inpatient setting. In the outpatient setting, nonpharmacological interventions associated with improved breathlessness were acupressure and reflexology (integrative medicine) (low SOE) and multicomponent interventions (combined activity and rehabilitation, behavioral and psychoeducational, and integrative medicine) (low SOE) lasting for a few weeks to months. Five of the 29 RCTs (17%) reported adverse events, although adverse events and study dropouts were uncommon. Conclusions and Relevance Findings of this review include the safety and association with improved breathlessness of several nonpharmacological interventions for adults with advanced cancer. Guidelines and clinical practice should evolve to incorporate nonpharmacological interventions as first-line treatment for adults with advanced cancer and breathlessness.