The standard of care for patients with unresectable, locally-advanced Non-Small Cell Lung Cancer (NSCLC) is definitive Radiation Therapy (RT) given with or without chemotherapy. However, outcomes with this modality are quite poor with 5-year survival estimates at 16%. A major barrier to improved outcomes is the development of Radiation-Induced Lung Injury (RILI). RILI occurs in 30% or greater of lung cancer patients and manifests on a spectrum from acute radiation pneumonitis, an inflammatory state occurring within weeks to 6 months of RT, to chronic radiation fibrosis, characterized by replacement of functional lung parenchyma with fibrotic tissue usually occurring months to years following therapy.
Studies have shown that radiation causes a state of oxidative stress characterized by increased generation of free radicals. Volatile reactive oxygen (ROS) and nitrogen (RNS) species have been shown in vivo and in vitro to accelerate lipid peroxidation, oxidize DNA and cellular proteins, as well as activate pro-inflammatory cytokines. Reducing oxidative stress would hypothetically prevent RILI and improve the therapeutic index of radiotherapy in lung cancer.
Flaxseed (FS) is a non-toxic, dietary wholegrain composed of omega-3 fatty acids and a lignan complex (FLC) with potent anti-inflammatory, antioxidant and anti-fibrotic properties. FS is the richest known source of the mammalian lignan precursor, Secoisolariciresinol Diglucoside (SDG), which is metabolized via enteric bacteria to Enterodione (ED) and Enterolactone (EL). As a plant phenolic, SDG was shown in vitro to have direct hydroxyl radical scavenging properties, limit the respiratory burst of White Blood Cells (WBCs) and to inhibit lipid peroxidation. Flaxseed has been reported to provide health benefits in several disease conditions including hypercholesterolemia, diabetes, menopause, cardiovascular health, metabolic syndrome and bone mineral metabolism.
In 2011, researchers from the Perelman School of Medicine at the University of Pennsylvania discovered that flaxseed can protect healthy tissues and organs from the harmful effects of radiation. Researchers found that a diet of flaxseed not only protects lung tissues before exposure to radiation, but can also significantly reduce damage after exposure occurs.
“There are only a handful of potential mitigators of radiation effect, and none of them is nearly ready for the clinic. Our current study demonstrates that dietary flaxseed, already known for its strong antioxidant and anti-inflammatory properties, works as both a mitigator and protector against radiation pneumonopathy.” – Melpo Christofidou-Solomidou, PhD, Research associate professor of Medicine, Pulmonary, Allergy and Critical Care Division
Dietary FS given post X-ray radiation therapy (XRT) mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage. Research suggests that dietary flaxseed may be clinically useful as an agent to increase the therapeutic index of thoracic by increasing the radiation tolerance of lung tissues. Flax Seed diet mitigated the deleterious effects of XRT by:
• Improving pulmonary hemodynamics and blood oxygenation levels
• Decreasing lung injury by lowering BAL protein levels
• Reducing pulmonary fibrosis by decreasing collagen content of lung tissues
• Reducing lung inflammation by decreasing WBC influx into the airways
• Oxidative modification of mouse lungs as evidenced by levels of lipid peroxidation
Studies have also revealed that dietary FS given prior to and post-thoracic radiation did not abrogate the tumoricidal properties of radiotherapy and that dietary FS given after RT improved survival.
An ideal radiation mitigator should be safe, effective, have a long shelf life and an easy route of administration. Flaxseed, due to its high content of lignans and omega-3 fatty acids, is a dietary supplement that has numerous medicinal, anti-inflammatory and antioxidant properties. Prolonged FS administration has not been associated with any significant toxicity. Therefore, researchers believe that flaxseed may be an effective, safe and cost-effective mitigator of the radiation damage.