OSA and Cancer?! Robert L. Owens, MD February 2018 Outline OSA - - PDF document

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OSA and Cancer?!

Robert L. Owens, MD February 2018

Outline

• OSA and Cancer?!
• Potential Mechanisms?
• Limitations of the Data
• OSA and Cancer occur all the time

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Thoracic pressure swings (↑LV aerload)

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Consequences

Neurocognitive

• Excessive daytime sleepiness
• Increased motor vehicle crashes
• Increased work‐related accidents
• Poor job performance
• Decreased quality of life

Cardiovascular

• Systemic hypertension
• Cardiac arrhythmias
• Myocardial ischemia
• Cerebrovascular disease
• Pulmonary Hypertension/ cor pulmonale

NEJM 1999

• As compared with those without sleep apnea, patients

with an AHI > 10 had an odds ratio of 6.3 (95% confidence interval, 2.4 to 16.2) for having a traffic accident.

• This relation remained significant after adjustment for

potential confounders, such as alcohol consumption, visual‐refraction disorders, body‐mass index, years of driving, age, history with respect to traffic accidents, use

• f medications causing drowsiness, and sleep schedule.

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Dog Model of Apnea (Brooks et al, JCI 99:106, 1997)

OSA and Hypertension

2005

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Fein JACC 2013

Atrial Fibrillation and OSA Pulmonary Hypertension

Sajkov AJRCCM 1999, 2002

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2013

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AJRCCM 2013

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What do people die from? An animal model…

Almendros ERJ 2012

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Reanalysis of WSCS…

Nieto AJRCCM 2012 Cancer‐free survivial

Outline

• OSA and Cancer?!
• Potential Mechanisms?
• Limitations of the Data
• OSA and Cancer occur all the time

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AHI vs. Intermittent Hypoxia An animal model…

Almendros ERJ 2012

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• Respir Physiol Neurobiol. 2013 May 1;186(3):303‐7. doi:

10.1016/j.resp.2013.03.001. Epub 2013 Mar 14.

• Intermittent hypoxia increases melanoma metastasis to the lung in

a mouse model of sleep apnea.

• Almendros I1, Montserrat JM, Torres M, Dalmases M, Cabañas

ML, Campos‐Rodríguez F, Navajas D, Farré R.

Sleep Apnea Cancer Morbidity & Mortality Carcinogenesis Tumor Growth & Metastasis

? ?

Altered Treatment Efficacy

?

A Complicated relationship

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2014

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NRF2 DNA mutations Sleep Deprivation Cancer progression Hypoxia HIF1,2 Reactive Oxygen Species (ROS) Circadian Clock mtDNA mutations Survival Cancer initiating cell death Sleep Apnea Glycolysis Immuno‐ deficiency Stress/ Cortisol/ Catecholamines Cytokines Angiogenesis Cancer progression

A Complicated relationship

Gozal Sleep Medicine Reviews 2016

Not just apnea?

• Circadian timing?

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Outline

• OSA and Cancer?!
• Potential Mechanisms?
• Limitations of the Data
• OSA and Cancer occur all the time

Limitations

• “Cancer” as a single entity
• Diagnosis from DRG codes – does not get into incidence vs.

aggressiveness

• Studies not specifically designed to look at cancer
• Little data on chronic sleep duration, stage, etc.

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Limitations

• Obesity as a confounder
• Risk factor for cancer and OSA
• Modifies depth of desaturation
• Usually quantified by BMI (which is imperfect)
• Is also modified by diet and life style

Limitations

• Animal studies have looked at tumor growth, aggressiveness
• Not de novo tumors
• Not the impact of OSA treatment on tumor growth

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Outline

• OSA and Cancer?!
• Potential Mechanisms?
• Limitations of the Data

Yes, in multiple cohorts Unclear which cancers Intermittent Hypoxia, Sleep Fragmentation Many questions remain

What to do in the meantime?

• Cancer and OSA occur together all the time
• Just by epidemiology/chance
• Some cancers may be particularly relevant (e.g. H+N cancers)
• Steroids, edema may increase weight
• Fatigue a major problem in patients with cancer
• More aggressive screening and treatment of OSA in people with

cancer could improve patient‐centric outcomes, and if it improves

• utcomes, so much the better

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Questions?

rowens@ucsd.edu