Dyspnea is a common and distressing symptom experienced by 19%-51% of patients with advanced cancer. Higher incidences are reported in patients approaching end of life. While the prevalence of dyspnea has been reported to be as frequent as pain in people with lung cancer, less attention has been paid to the distress associated with dyspnea. This review of the literature was undertaken to investigate how dyspnea has been assessed and whether breathlessness in people with lung cancer is distressing. Using a predetermined search strategy and inclusion criteria, 31 primary studies were identified and included in this review. Different outcome measures were used to assess the experience of dyspnea, with domains including intensity, distress, quality of life, qualitative sensation, and prevalence. Overall, the studies report a high prevalence of dyspnea in lung cancer patients, with subjects experiencing a moderate level of dyspnea intensity and interference with activities of daily living. Distress associated with breathing appears to be variable, with some studies reporting dyspnea to be the most distressing sensation, and others reporting lower levels of distress. However, taking into account the prevalence, intensity, and distress of dyspnea, the general consensus appears to be that the experience of dyspnea in people with lung cancer is common, with varying degrees of intensity, but involves considerable unpleasantness. Thus, if dyspnea and pain are both distressing sensations for people with lung cancer, this has potential implications for both clinical and academic areas with regards to both management strategies and further research.
There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non-small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15-30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or to either programmed cell death-1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.