Abstract

Sleep disorders have emerged as highly prevalent conditions, and along with improved understanding of such disorders, increased attention has gained the evidence that perturbation in sleep architecture and continuity may initiate, exacerbate, or modulate the phenotypic expression of multiple diseases including cancer. Furthermore, obstructive sleep apnea (OSA) has recently been implicated in increased incidence and more adverse prognosis of cancer in humans. This study was designed to confirm the high prevalence of OSA in human malignancies and assess its prognostic relevance in metastatic colorectal carcinomas (mCRCs). A prospective cohort of 52 subjects, affected by solid histologically confirmed metastatic malignancies, was analyzed, and among them, 29 mCRCs were studied for the prognostic role of OSA. OSA was diagnosed in 34.6% (18/52) of patients with a statistically significant difference in apnea-hyponea index between OSA and non-OSA subgroups (14.2 ± 12.2 vs. 2.1 ± 1.5, p < 0.01). Consistently, OSA was diagnosed in 34.5% (10/29) of mCRCs with lower rates of first-line therapy disease control in OSA compared to non-OSA patients (60% in OSA vs. 94.7% in non-OSA, p=0.03). Of note, progression-free and overall survival rates were significantly shorter in OSA (respectively, 9 and 22 months) compared non-OSA (20 and 40 months) mCRC patients (HR = 2.63; 95% CI 0.88–7.84, p=0.01 for PFS; HR = 3.93; 95% CI 1.13–13.73, p < 0.001 for OS). Finally, the multivariate analysis showed that OSA is an independent prognostic factor for PFS (p=0.0076) and OS (p=0.0017) in this cohort. Altogether, these data suggest that OSA is a potential clinical marker predictor of poor prognosis in patients with mCRC.

Highlights

  • Obstructive sleep apnea (OSA) is a disorder characterized by frequent subobstruction/obstruction of upper airways during sleep with intermittent hypoxia and sleep fragmentation

  • All-cause mortality risks are increased with sleep-related breathing (SDB) disorders severity, but the association between SDB and cancer mortality seems stronger and a link has been proposed between intermittent hypoxemia and the aggressiveness of human cutaneous malignant melanoma [7]

  • E relationship between OSA and Disease control rate (DCR), PFS after firstline therapy, and cancer-specific mortality was evaluated in the cohort of patients affected by metastatic colorectal carcinomas (mCRCs) (Table 2)

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Summary

Introduction

Obstructive sleep apnea (OSA) is a disorder characterized by frequent subobstruction/obstruction of upper airways during sleep with intermittent hypoxia and sleep fragmentation. It is associated with systemic diseases such as hypertension, cardiac arrhythmias, cerebral and cardiovascular events, type 2 diabetes, postoperative complications, and several other morbidities [1,2,3,4]. Recent studies in animal models and humans showed that sleep apnea and intermittent hypoxia may increase the risk of developing cancer [5] and may worsen its prognosis by increasing cancer progression and mortality [6]. To Journal of Oncology date, the relationship between OSA and cancer prognosis is still debated [10]

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