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Systemic effects of radiation

• While radiation’s effects are mostly localized to the target tissues and those nearby, there are some general effects that we should know about. 
• (1) Fatigue: 
  • It’s a mystery why this happens (possibly )
  • It’s by far the most common and most persistent effect of radiation. 
    • It can be very mild in some, or profound and disabling in others.
    •  It can last for weeks or months.
      • A rule of thumb from our radoncs to help with counseling your patients: however long your patient’s radiation course lasted, is going to be how long it takes for them to feel closer to their baseline. 
• (2) Cytopenias: we often chalk up cytopenias to prior radiation, but is this the right way to think about it?
  • Cytopenias are generally proportional to the amount of bone marrow in the field. 
    • Ex. pelvic and spinal radiation are higher-risk for cytopenias.
  • However, it’s to see cytopenias from radiation directly, as compared to chemotherapy (or combined chemoradiotherapy). 
  • If radiation-associated cytopenias are present, they should only last for as long as the radiation itself. 
    • If cytopenias persist after treatment with radiation alone, conduct a thorough cytopenia workup. It is unlikely to be the radiation itself. 
• (3) Immunosuppression: radiation has variable effects on the immune system. It’s a bit of a toss-up. 
  • Radiation and chemotherapy combined can cause synergistic immunosuppression. 
    • And as with cytopenias, any immunosuppressive effect from radiation should only last as long as the radiation itself.
  • Radiation can also activate the immune system through mechanisms like the “ effect”, in which radiation causes the immune system to attack the tumor. 
    • It’s rare, but a neat proof of concept: radiation’s effect on the immune system is variable, and hard to predict. 
      • If you’re curious, a review article summarizing some interesting case reports.
• If you are ever wondering “is this a radiation-associated side effect?” remember these are tough diagnoses to make and are largely diagnoses of exclusion – your friendly neighborhood radonc is an invaluable resource!

Effects of radiation by site

• The “what”, “when”, and “where” of radiation are key to understanding its effects. The most important of all is the “where”. Radiation is location-specific – think about the path of the beam, and the nearby structures. 
• (A) Lung: 
  • Divide these into short- and long-term effects, because radiation is also timeframe-specific. Think -itises versus -osises.
    • Short-term effects (weeks to months): 
      • Irritation to those deeper structures (esophagitis, pneumonitis, and pericarditis). 
      • A point about radiation pneumonitis: this is a diagnosis of exclusion.
        • Imaging may not help as much since the majority of patients receiving radiation to their chest will have post-radiation findings on chest imaging regardless of whether they have clinically-significant pneumonitis.
        • notes a 78% chance of finding an infiltrate 3-9 months after breast radiation, even though we know the incidence of symptomatic radiation pneumonitis is quite low in this population. 
        • Keep in mind, radiation pneumonitis is even less common after SBRT, because it is highly-targeted and spares healthy lungs. Be extra careful to keep your differential broad in patients who received SBRT. 
          • Radiation Pneumonitis has a rough incidence of overall after lung EBRT, but approximately with lung SBRT
    • Long-term effects (months to years) include fibrosis which is often (but not always) consequent to that irritation. 
      • Ex: Pulmonary fibrosis, esophageal strictures. 
  • A further distinction is depth – radiation is depth-specific. 
    • We can’t lump lung radiation and breast radiation together for this reason. 
    • You can counsel your patients – they won’t see dermatitis with lung radiation. 
• (B) Breast: 
  • Compare and contrast with lung radiation:
    • Rememeber radiation is depth-specific!
      • Tumor may go all the way up to the skin, so dermatitis is very common (up to %). 
    • and pericarditis are rare, especially with our newer techniques (1-5% for pneumonitis). 
      • You may see radiation pulmonary fibrosis and cardiac disease due to breast radiation long ago, because we used much higher doses and wider fields in that era. Unlikely with modern radiation.
  • You can reassure your patients that radiation is not disfiguring – even with breast radiation, the skin changes would generally only be noticed by a partner.
• (C) Prostate: 
  • Think about the structures near the prostate
  • Short-term: proctitis, cystitis, rectal bleeding, erectile dysfunction
    • Just like pneumonitis, radiation proctitis/rectal bleeding are diagnoses of exclusion. Conduct a thorough workup, just as you would for any other patient. 
  • Long-term: strictures, ileus, obstructions.
    • Osteoporosis and pelvic insufficiency fractures
      • Bisphosphonates have not been shown to help with radiation-associated fractures unfortunately, though they can be helpful with metastatic disease
• (D) Brain: 
  • Brain radiation tends to involve more advanced techniques like SRS (often branded as “gamma-knife”) to avoid collateral damage.
  • Short-term: 
    • Fatigue is very common. 
    • There can be a wide range of neurological effects, such as focal neurologic deficits! 
      • Of course, in your patients with intracranial disease, you’re going to be worried about the disease as the primary cause. 
  • Long-term: 
    • With whole-brain radiation (WBRT), people can get significant fatigue and memory problems, with up to of patients experiencing cognitive decline (remember, this is in WBRT – in contrast to SBRT/SRS which are very focused and do not typically cause memory loss). 
    • Memantine can help with cogntive decline

Contributors

Shreya Trivedi, MD, ACP Member – Host, Editor
Samantha Kumarasena, MD – Host, Editor, MOC questions
Daphna Spiegel, MD - Guest
Matt Abrams, MD* - Guest

Reviewers

Sarah Stevens, MD
Julian Hong, MD*

* Matt Abrams, MD – Consultant: Medtronic

* Julian Hong, MD – Grant/ Contract: F. Hoffman-La Roche

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date:  May 31, 2023

Expiration Date: May 30, 2026

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