Managing Radiation Therapy Side Effects with Genetic Testing

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Radiation therapy is a successful treatment against many types of cancer. Unfortunately, some survivors will experience radiation toxicity from the treatment, with the most problematic side effects manifesting years later and potentially severely impacting their quality of life. Although the application of advanced technology to radiation has decreased toxicity for patients in general, up to 30% of patients still experience long-term side effects.

Therefore, it is critical to identify patients who are overly sensitive to radiation so that they have the opportunity to prevent post-radiation complications. In the past, it was challenging to determine which patients were at increased risk of radiation toxicity. Fortunately, recent advances in health science have shown a link between unique genetic biomarkers and their ability to predict an individual’s sensitivity to radiation.

In this blog, we will discuss the history of radiation therapy, how it works, potential side effects, the new understanding of the relationship between genetics and the risk of radiation toxicity, and how this information can help you personalize your cancer treatment plan.

What is Radiation Therapy?

First medical X ray by Wilhelm RAΒΆntgen of his wife Anna Bertha Ludwigs hand 18951222 1 copy
First X-ray of Anna Bertha Ludwig’s hand – 1895.

While studying cathode rays, German physicist Wilhelm Conrad Roentgen accidentally discovered an invisible ray he called an X-ray.1 He demonstrated the ability of this type of ray to penetrate human skin and reveal bones.2 X-rays quickly gained popularity in medicine. However, physicians observed that the high-energy radiation they emitted damaged soft tissue. This observation paved the way for using radiation to precisely target and kill tumorsβ€”a cancer treatment known as radiation therapy.

Fast forward about 130 years, and radiation therapy has become a common and successful treatment for cancer. In fact, more than half of cancer patients will receive some form of radiation therapy as part of their treatment plan.3 This means that more than a million new cancer patients will receive radiation therapy this year.4

How Does Radiation Therapy Work?

There are two main delivery methods for radiating cancer cells: internal radiation therapy, commonly known as brachytherapy, and external beam radiation therapy (EBRT). Brachytherapy uses small, solid radiation sources to administer treatment within or near the tumor. EBRT uses cutting-edge tools and technology (IMRT, 3D-CRT, SBRT, CyberKnife, etc.) to precisely deliver high-intensity beams (protons, photons, and/or neutrons) from outside the body to tumors within the body while minimizing damage to nearby healthy organs and tissues.5

Fractionation divides a patient’s total radiation dose into smaller, usually daily doses (fractions) over a set time frame. The concept of fractionation hinges on the ability of normal cells to repair themselves between fractions, which helps lower the risk of side effects from radiation.

The three most common fractionation schedules6 are as follows:

  • Conventional fractionation (~35–45 low radiation doses over 8–10 weeks)
  • Moderate hypofractionation (~20–25 medium radiation doses over 4–5 weeks)
  • Ultra-hypofractionation (~5–7 high radiation doses over 5–10 days)

Ultra-hypofractionation has increased in popularity over the years since it shortens the time the patient spends receiving treatment, and with advanced technology, it can generally be done safely.

mk radiation regimens pc managing radiation side effects post

While the cure rates and overall toxicity rates of radiation treatments using small or large radiation fractions are similar, the genetic risks of side effects appear to differ between these radiation treatment approachesβ€”a topic we will further discuss below.

Side Effects of Radiation Therapy

Even with the precision of EBRT and dose fractionation, radiation treatment can still cause toxicity to healthy organs and tissues. Radiation toxicity manifests as side effects, often known as adverse events (AEs). Radiation side effects can occur early in therapy (acute or short-term) or later in treatment (late-onset). Late-onset radiation toxicity affects approximately 10–30% of individuals receiving radiation therapy.

Late-onset side effects can develop six months to years after radiation therapy is complete, ranging from minor discomfort to life-threatening problems that significantly impair your quality of life. These radiation side effects are usually permanent, can worsen with time, and may reflect specific damage to the treated area.7 Some of the causes include radiation-induced tissue scarring (fibrosis), atrophy, blood vessel damage, and neurological impairment.8

Physicians use a grading scale from 0 to 5 to report the severity of each side effect resulting from radiation therapy.9

This information helps physicians better assess the potential impact of the side effects on the patient and make informed decisions about how to manage it. In general, grade 2 or higher side effects are considered especially problematic for patients.

mk blog AE grades

Genetics and Its Link to Predicting Radiation Toxicity

What if your genetics could predict the risk of late-onset toxicity from different courses of radiation therapy? This information allows your doctor to choose the most effective cancer treatment plan while maintaining your quality of life years after treatment.

The ability to predict the risk of toxicity due to radiation therapy is a reality.

Genetic Profiling: Identifying Patients at Risk Using Their Genes

Genetic profiling uses genetic biomarkersβ€”unique changes in the DNAβ€”to find people who are at higher risk of radiation toxicity. This information enables doctors to customize patient cancer treatment plans to reduce their risk and prioritize their health. But first, we have to identify the biomarkers that make this possible.

Dr. Joanne Weidhaas, a radiation oncologist at UCLA Medical Center and MiraKind’s founder, co-discovered the KRAS-variant in 2006, the first of a new class of inherited genetic biomarkers with important health implications.10 Further research discovered a link between the KRAS-variant and an increased risk of lung10, ovarian11, and breast cancer12, as well as other malignancies13,14.

Interestingly, they also discovered that the KRAS-variant could predict a risk of radiation toxicity for head and neck squamous cell carcinoma (HNSCC)15 and non-small cell lung cancer (NSCLC)16 patients. In each study, KRAS-variant patients were more likely to develop late-onset grade 3 and 4 side effects. The discovery of the KRAS-variant and its correlation with the body’s response to cancer treatment paved the way for the discovery of other, biologically similar variants and their link to radiation toxicity. Dr. Weidhaas and colleagues uncovered genetic biomarkers linked to radiation toxicity in patients with either prostate cancer17 or soft tissue sarcomas (STS)18. Patients with these biomarkers were more likely to experience late-onset grade 2 or higher side effects after radiation therapy. Importantly, they found biomarkers that were unique for each fractionation type (CFRT vs. SBRT), suggesting that these genetic biomarkers are fractionation-dependent predictors of late radiation toxicity.17

Together, these findings show that individuals possess unique genetic biomarkers that not only help doctors identify who is at risk of radiation toxicity but also predict that risk based on fractionation.

Knowledge is Power: Do Your Genetics Predict a Risk of Toxicity?

At MiraKind, one of our pillars is to provide patients with access to meaningful genetic testing. Research conducted by Dr. Weidhaas and colleagues has made this testing possible. Through genetic profiling, our tests can predict radiation toxicity and determine which course of radiation therapy is safest for each individual.

For instance, for prostate cancer patients, stereotactic body radiation therapy (SBRT) and conventionally fractionated radiotherapy (CFRT) are both effective treatment options. Although both methods target the cancerous tissue, they differ in how they deliver radiation. SBRT administers higher doses of radiation in fewer sessions over a shorter time frame. In contrast, CFRT delivers smaller doses of radiation over a longer duration, usually extending across many weeks.

While both treatment options are highly effective in treating prostate cancer, there is a risk of radiation toxicity that affects the urinary system. This toxicity manifests as frequent urination, urgency to urinate, urinary leakage, urinary tract pain, and blood in the urine, all of which can significantly affect an individual’s quality of life. PROSTOXTM testing can predict the risk of these side effects using unique genetic biomarkers that identify patients at risk of toxicity for each treatment regimen. This enables the creation of personalized treatment plans that balance effective cancer treatment with minimized side effects.

mk blog prostox resulst managing rad side effects

Make your cancer treatment personal.

MiraKind testing can help determine if you are at an increased risk for long-term side effects from radiation therapy. Your doctors can use this information to make more informed decisions if they find you at a higher risk, which may include choosing one fractionation schedule over another or considering alternative treatment approaches.

You can access PROSTOX through MiraKind. Learn more about these tests.

Don’s Journey with Genetic Testing

When Don Tate received borderline-high results from his prostate-specific antigen (PSA) test, his primary physician strongly encouraged him to consult a urologist to explore the possibility of prostate cancer. Yet, despite ongoing evaluations, no definitive answer emerged. Over the next three years, Don faced a barrage of conflicting opinions, leaving him uncertain whether treatment was necessary.

With so much confusion over his prostate cancer diagnosis, Don found comfort in a call from Dr. Weidhaas to review his PROSTOX test results. Read more of Don’s Story: Navigating Prostate Cancer Treatment


References

  1. https://www.cancer.org/cancer/understanding-cancer/history-of-cancer/cancer-treatment-radiation.html
  2. https://en.wikipedia.org/wiki/File:First_medical_X-ray_by_Wilhelm_R%C3%B6ntgen_of_his_wife_Anna_Bertha_Ludwig%27s_hand_-_18951222.jpg
  3. https://www.cancer.org/cancer/managing-cancer/treatment-types/radiation/basics.html
  4. https://www.cancer.gov/about-cancer/understanding/statistics
  5. https://my.clevelandclinic.org/health/treatments/17637-radiation-therapy
  6. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy/external-beam
  7. https://www.nature.com/articles/s41572-019-0064-5
  8. https://www.nature.com/articles/nrc1950
  9. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf
  10. https://aacrjournals.org/cancerres/article/68/20/8535/541399/A-SNP-in-a-let-7-microRNA-Complementary-Site-in
  11. https://pubmed.ncbi.nlm.nih.gov/20647319/
  12. https://pubmed.ncbi.nlm.nih.gov/21435948/
  13. https://pubmed.ncbi.nlm.nih.gov/27620744/
  14. https://pubmed.ncbi.nlm.nih.gov/27221928/
  15. https://jamanetwork.com/journals/jamaoncology/fullarticle/2594275
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC10566451/
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC8979583/
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC7189949/

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Any discussion of medical management options on this website is for general informational purposes only and does not constitute a medical recommendation. All medical management decisions should be made based on consultation between each patient and his or her healthcare professional.

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