Time Stamps

  • 02:37 Systemic Radiation Side Effects
  • 14:29 Lung Radiation Side Effects
  • 18:25 Breast Radiation Side Effects
  • 21:31 Prostate Radiation Side Effects
  • 24:54 Brain Radiation Side Effects

CME-MOC

Video of Rad Onc Physiology

Whiteboard Animation Video

Show Notes

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 cytokine-related)
    • 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 much less common 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 “abscopal 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, here’s 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.
          • One study 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 15-40% overall after lung EBRT, but approximately 10% 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:
      • Remember radiation is depth-specific!
        • Tumor may go all the way up to the skin, so dermatitis is very common (up to 90%). 
      • Pneumonitis 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 50% 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 cognitive decline

Transcript

Dr. Shreya Trivedi: Welcome to “5 Pearls” podcast, bringing you high-yield, evidence based pearls. Today, is part 2 of radiation oncology, diving into side effects and maybe busting some myths along the way. Joining me today is Dr. Sam Kumarasena.

Dr. Sam Kumarasena: Welcome back everyone! I’m Sam, a second-year resident at Beth Israel Deaconess Medical Center. Really looking forward to our second part of this deep dive! Rad Onc 2: Electric Boogaloo. 

Dr. Shreya Trivedi: Can you explain what that cultural reference is? If there is anyone like me who did not understand it the first time?

Dr. Sam Kumarasena: Yeah! I think there’s this old movie called Breakin 2, where, it was cult classic really bad, so bad, it’s good, and then they released a sequel, and they ended it in Electric Boogaloo! I just thought we’d tack that on.

Dr. Shreya Trivedi: Again, I learn so many good cultural references through making these episodes! Everyone, if you haven’t already, go ahead and listen to Part 1. It’s a really good foundation for radiation oncology!  And also look out for a short Youtube whiteboard animation that Sam created, that really goes over some interesting physiology on Radiation that was a bit outside the scope of this episode. And with that, let’s get started on the pearls we’ll be covering today! Quiz yourself. Remember, the more you test yourself, the deeper your learning gains.

Dr. Sam Kumarasena: Pearl 1 – Systemic Radiation Effects.

Dr. Shreya Trivedi: To what extent does radiation affect fatigue, cytopenias, and immunosuppression?

Dr. Sam Kumarasena: Pearl 2 – Lung Radiation Side Effects.

Dr. Shreya Trivedi: What are short- and long-term side effects we see with radiation to the lung?

Dr. Sam Kumarasena: Pearl 3 – Breast Radiation Side Effects.

Dr. Shreya Trivedi: What are short- and long-term side effects we can see with radiation to the breast?

Dr. Sam Kumarasena: Pearl 4 – Prostate Radiation Side Effects.

Dr. Shreya Trivedi: What are short- and long-term side effects we can see with radiation to the prostate?

Dr. Sam Kumarasena: And wrapping it up with Pearl 5 – Brain Radiation Side Effects.

Dr. Shreya Trivedi: What are short- and long-term side effects that we can see with radiation to the brain?

Dr. Shreya Trivedi: Okay, I’m really excited for this episode because I think a lot of us will be seeing a patient who had prior radiation and asking ourselves, hm, is that symptom the person is feeling an adverse effects of radiation or something else? So, maybe we can start big picture and think about the more generalizable symptoms, right? And I think the biggest generalizable symptom that our patients often feel is fatigue. 

Dr. Sam Kumarasena: That’s a good one! I am wondering, why do patients get fatigued after radiation, anyway?

Dr. Matthew Abrams: The fatigue associated with radiation, it’s actually poorly understood exactly why patients feel tired. The thought is that there is a cytokine storm or cytokine release, which may be triggering some kind of a subclinical inflammatory, systemic inflammatory process, um, that may be contributing. 

Dr. Shreya Trivedi: That’s Dr. Matt Abhrams, a radiation oncologist at BIDMC. Yep, and when in doubt, it’s those cytokine storms, always causing havoc!

Dr. Sam Kumarasena: Yep, those darn cytokine storms!

Dr. Matthew Abrams: Fatigue or tiredness that can take the longest to get, to get better. I definitely have patients that I’ve treated, uh, that still have persistent fatigue sometimes six to 12 months later. Um, and it is highly variable, once again from patient to patient, the area that you’re treating.

Dr. Daphna Spiegel: The fatigue for most people tends to start around halfway through their radiation course and then it kind of gets a little bit worse and worse as we go through things sort of peaking towards the end of the radiation because it’s a cumulative effect. I often counsel patients that however long you are on treatment for might be how long it might take you to feel close to back to your baseline. So if you were on treatment for four weeks or six weeks, it’s not that you won’t get better during the four or six weeks after treatment, but it might take those four or six weeks after treatment’s done for you to really feel a noticeable improvement.

Dr. Sam Kumarasena: That was a super helpful rule of thumb from Dr. Spiegel, an assistant professor in radiation oncology at Harvard Medical School. She specializes in breast and GYN malignancies at BIDMC. Let’s recap that, however long your patient’s radiation course lasted, is going to be generally how long it takes for them to feel closer to their baseline. 

Dr. Shreya Trivedi: That is helpful! Okay, so thats fatigue. Let’s talk about another side effect we see commonly – cytopenias. I think we’ve all seen patients that get admitted for an unrelated reason, their blood work comes back, it shows some cytopenias, and of course, radiation gets put on the differential. Is that the right way to think about it?

Dr. Matthew Abrams: There’s also this temporal relationship, as well. During treatment we often see these kind of cytopenias, but like years down the road, would we still see them? Uh, that’s harder to know. Um, you can definitely see kind of bone marrow changes on CT and MRI after treatment, but whether that has any lasting effect, uh, that could still cause cytopenias down the road is much less clear. So, you know, the bone marrow can regenerate itself, right? So, when we’re giving radiation, it’s not a myeloablative radiation. I’d be very careful about hanging your hat on cytopenias years down the road on prior radiation. I would almost use it as a diagnosis of exclusion to make sure that you, you know, are thinking about other things, other more serious things like MDS.

Dr. Shreya Trivedi: Speaking of MDS, or myelodysplastic syndromes, we should be aware that secondary MDS or acute myeloid leukemia, AML, are small but very real risks after radiation exposure. And particularly with MDS, its been cited that about 20% of all MDS cases are secondary to either radiation or chemo.

Dr. Sam Kumarasena: And just like we talked about, the timing is really critical here. Cause sure, during treatment you can see cytopenias with radiation or chemo. But say you have a cytopenia after radiation, years down the line. Secondary MDS, or potentially a leukemia, are absolutely on the differential. Now with that, let’s get back to cytopenias in general. Maybe thinking about when we are at highest risk for seeing cytopenias.

Dr. Shreya Trivedi: And the highest risk of cytopenia probably depends on how much radiation a patient got? Or the site of radiation?

Dr. Matthew Abrams: The more bone marrow you radiate, the higher the risk of causing a cytopenia. So once again, if I’m treating, I don’t know, a humeral met, you know, am I gonna expect a cytopenia? No. If I’m treating their entire spine with cranial spinal of radiation, could I see some cytopenias? Yeah, I definitely could, would i prophylaxis them with Bactrim for PCP, maybe, I don’t know. Sure. Um, kind of depends.

Dr. Sam Kumarasena: Got it. We’ll think of places with lots of bone marrow. Like, radiation to the spine, bowel, prostate, GYN tumors, all are probably high risk. But it also probably, kind of depends…right?

Dr. Shreya Trivedi: Yeah, so it really does depending, right. It reminds me of one my pet peeves. I often hears people throw out on rounds “oh, this patient got radiation, they must be immunocompromised!” And this bugs me so much, because I don’t know if  lumping everyone with a history of radiation under the immunocompromised bucket is right? My gut says, that’s not accurate, but I’m curious how the rad oncs think about radiation induced immunosuppression?

Dr. Sam Kumarasena: Yeah, so our rad oncs said once again, it kind of comes down to the amount of radiation the patient receives, and how much of that bone marrow is actually getting radiated. And then on top of that, you add chemo in the mix, which really muddies the waters on how immunocompromised they might be.

Dr. Daphna Spiegel:  For most patients it is not going to be the radiation itself that is going to be causing the cytopenias or the immune suppression. More often it’s caused by the chemotherapy that’s given concurrently with radiation. But there might be some added component of immune suppression or cytopenia from the radiation, but the majority is from the chemotherapy that they’re getting. If you’re talking about treating rectal cancer, again, often giving that with concurrent chemotherapy and it’s really the chemotherapy that tends to be the culprit rather than the radiation. 

Dr. Shreya Trivedi: So thats a great point, usually the immunosuppression is from the chemo. But if there is radiation to an area with a lot of bone marrow, it could definitely add to the immunosuppression. And with chemoradiation on top of it, it’s going to be pretty synergistic, right. It’s not 2+2 equals 4 kind thing, it’s going to be more than that. 

Dr. Sam Kumarasena: I think one thing that really surprised me, was that radiation can also activate the immune system too! Which is pretty weird!

Dr. Matthew Abrams: On the other end, sometimes we actually see immune responses and patients are getting immune therapy to other sites of disease. That’s called the “abscopal effect.” So once again, it’s, it’s really unknown. So you can actually see augmented immune responses after radiation sometimes. So, who knows!

Dr. Shreya Trivedi: Wait, what? What’s this “abscopal effect”?

Dr. Sam Kumarasena: I think the basic idea, is that radiation is going to cause tumor cells to break down and release their contents, right? And then the immune system gets activated against the tumor, and then attacks the tumor throughout the body. So, effectively what you see, is that you give radiation to one site, and then you see all the tumors, throughout the body, shrinking! Super rare, but it’s a neat concept. 

Dr. Shreya Trivedi: Oh my gosh, now I feel like it’s a, it’s a toss up. Radiation can suppress the immune system, or activate it, or maybe not affect it at all. I guess we really can’t lump it all under the immunocompromised bucket! So I’m curious are there any objective measures, other than cytopenias, that we can tell if someone is more immunocompromised than others? 

Dr. Matthew Abrams: I counsel all my patient on this, is even if we treat you with radiation and there’s no, um, objective way to measure your immunocompromised status, as in we do bloodwork and we don’t see any significant cytopenias. I think we know that the immune system, that person’s immune system is not at the same level as the average person. Um, and sometimes that’s almost like an intangible amount. When I see patients in clinic, my first question during consult is, how many covid boosters have you gotten and when’s your next one? Um, and when’s your flu shot? You should get it. That being said, I think in general after treatment, the risk of quote unquote immunocompromised status is much, much lower. Um, I don’t classically consider anyone immunocompromised after, generally we radiate them. Um, but once again, it kind of depends on each particular situation.

Dr. Shreya Trivedi: Okay, I guess as much as we wanted a real, concrete answer about immunocompromise, it’s just as Dr. Abrams says – it’s often an intangible amount, but I do think we can breathe a bit easier about someone’s immunocompromise status and think a bit more precisely about it if their radiation has already been done and if there was no concurrent chemo involved.

Dr. Sam Kumarasena: Absolutely! Maybe, let’s pause here, to summarize these big three generalized potential side effects of radiation. The big one, we first talked about, is fatigue. Which, again, is super variable, but we have this helpful rule of thumb. After the radiation’s done, it might take roughly the duration of the radiation course, for your patient to feel more like themselves. With cytopenias, if you’re radiating an area with a lot of bone marrow, like the pelvis or spine, you might see low counts, but you should only see them during the time your patient’s getting radiated. Otherwise, you’re pretty much in the clear. And after their radiation is done, let’s remember, that it’s unlikely to be the culprit for cytopenias, so we should be really keeping out differentials wide open. And the same thing really goes for immunosuppression. You’re really should only see it during radiation.

Dr. Shreya Trivedi: I think one reassuring thing is that that radiation oncologists really do follow up with their patients frequently and can help us triage some of these side effects.

Dr. Matthew Abrams: I always counsel patients, you know, we see our patients weekly and, and often, you know, very frequently and follow up as well. It’s not like they’re gonna develop side effect and we’ll send them out in a boat in the middle of the ocean. Radiation oncologists, uh, you know, see patients for decades after treatment. So we’re often the ones following them, um, afterwards, both from a cancer surveillance standpoint, but also a, uh, toxicity reevaluation standpoint as well. As I was always taught we’re oncologists first, we just happened to use radiation as our drug of choice.

Dr. Shreya Trivedi: Yep, rad oncs are oncologists first by training! They don’t just do radiation, but they are great colleagues to partner as issues may arise for these patients. 

Dr. Shreya Trivedi: Okay, now that we talked about the general side effects, now let’s get a bit more into specific complications that arise.

Dr. Daphna Spiegel: The main thing to remember is side effects really only happen in the location where we’re aiming the radiation. So if I treated this patient for a brain tumor but later on they experience a small bowel obstruction, even though that could be an unusual complication from radiation aimed at the bowel, it has nothing to do with the fact that I treated their brain tumor with radiation. And while that might be a more extreme example because these two areas are very far from one another, I think sometimes it’s interesting to see what gets attributed to radiation. 

Dr. Sam Kumarasena: I think we have to remember that radiation is location-specific. So its side effects will also be location-specific.  

Dr. Shreya Trivedi: Since radiation is location-dependent, let’s focus on the main sites of radiation. So, I think the “Big Three” being lung, breast, and prostate. And just for kicks, we’ll also get into some brain radiation at the end. 

Dr. Sam Kumarasena: We’ll then divide our side effects, for each of those sites, into acute and chronic. And I think a lot of us learned in med school, there are acute side effects, which generally happen during or shortly after the treatment, on the order of weeks or months after. Then there are the late side effects, which happen years to decades down the road.

Dr. Shreya Trivedi: Yeah, that’ll be good to go over! I forgot, all of it. So, why don’t we start off with the lung.

Dr. Daphna Spiegel: So, even if you’re treating the lung tissue if you have to treat lymph nodes or you’re treating a lesion that’s close to the middle of the chest, the esophagus can get irritated from the radiation and that can cause patients to sometimes feel like they either have something, they kind of feel like there’s something in their chest or have some pain when they’re swallowing or feel like they can’t get food to go down the right way. That’s temporary. It does get better with time.

Dr. Shreya Trivedi: Great! I love telling patients when things like radiation esophagitis will get better with time!

Dr. Sam Kumarasena: And that esophagitis in the acute period, reminds me that we can think, short-term radiation effects are words that end with “itis.” Think of like dermatitis, esophagitis, or pneumonitis. And we think of these “itis” effects as acute because that inflammation comes from the direct effect of the radiation, right? But on the other hand, with the longer-term side effects, we think of the “osises.” Such as skin or pulmonary fibrosis. Key point! “itis” in the short-term, “osis” in the long-term.

Dr. Shreya Trivedi: Yeah! I love that framework of thinking “itis” for acute and “osis” as long-term. And I think in addition to radiation esophagitis, the other one we hear about the lung is radiation pneumonitis. But, for me, that timeline is pretty fuzzy of when that happens.

Dr. Matthew Abrams: Irritation of the lung from radiation is called radiation pneumonitis, uh, usually presents about, I’d say about six to 12 months actually after radiation finishes, but it can happen at any point in time. 

Dr. Sam Kumarasena: One of our reviewers pointed out that at the earliest, you’ll see pneumonitis, 6 weeks after their radiation, not usually during. Then, after 12 months, the risk of pneumonitis goes down, and the risk of fibrosis goes up. But keep in mind, as Dr. Abhrams pointed out, pneumonitis can really happen at any point.

Dr. Shreya Trivedi: And I think the other thing, teasing apart radiation pneumonitis can just be hard in a patient with fever, cough, and shortness of breath, just from the fact that because they have had radiation, their chest imaging will have some sort of changes. 

Dr. Sam Kumarasena: That’s a great point, it can be really hard to interpret. Especially since we’re not going to know if the area of the infiltrate we’re seeing is in the same exact distribution of where the radiation went in their chest.

Dr. Shreya Trivedi: Yeah, and thankfully at the end of the day, this is a clinical diagnosis, and we can always ask pulmonologist or radiation oncologist, whoever is taking ownership of it in the hospital, to help, kind of, assess that out a bit more. 

Dr. Daphna Spiegel: I tell patients anytime that we might treat your breast cancer or lung cancer, if you develop symptoms that could be consistent with radiation pneumonitis, we first have to make sure that it’s not something else because common things being common, it’s going to be a regular respiratory illness that’s causing your shortness of breath and low grade fever rather than the radiation. But if you’re not getting better with all of the normal things, then we can think about whether or not it might be related to radiation.

Dr. Sam Kumarasena: Okay! Moral of the story, radiation-associated effects are generally diagnoses of exclusion. So by all means, we can put these things on our differentials. But our initial workup shouldn’t differ, whether your patients have gotten radiation or not.

Dr. Shreya Trivedi: Yeah and I think this brings us back to what we learned in Part 1, right? Where we think about the different types of radiation and if we had a patient who had a handful of SBRT to a solitary lung nodule, then their fever and cough is pretty unlikely to be symptomatic radiation pneumonitis. And, it’s probably something else!

Dr. Sam Kumarasena: Wow, that’s a fantastic throwback!

Dr. Shreya Trivedi: Ah, thanks! Yeah.

Dr. Sam Kumarasena: Let’s summarize this pearl real quick. I think the most important point here, is that radiation-associated side effects are diagnoses of exclusion. Especially with radiation pneumonitis. Your patient with cough and fever who got radiation a few weeks ago, should still undergo the same pneumonia workup as every other patient. And as a heads-up, they’ll probably have post-radiation changes on their imaging, which are going to be hard to interpret.

Dr. Sam Kumarasena: Let’s move on now to breast radiation!

Dr. Shreya Trivedi: So I’m thinking breast radiation is of a similar distribution as lung radiation. So, side effects are the same, too?

Dr. Sam Kumarasena: Not quite, actually! Because breast radiation is targeted more superficially, the side effects are also going to be more superficial than what we saw with lung radiation. 

Dr. Matthew Abrams: So to deliver dose to the entire breast tissue, there is a dose of radiation to the skin surface. And in doing so, patients get a skin reaction that’s pinking and reddening of the skin. Sometimes it can blister or peel.

Dr. Daphna Spiegel: Sometimes the breast can look a little bit smaller because that scar tissue causes the breast to actually contract a little bit. Sometimes there could be some persistent swelling, so the breast might actually look a little bit bigger, not smaller and what I tell patients is, even though there might be these slight changes, they’re usually only something that you or a partner would notice. They are not big enough changes that anybody else would notice when you’re wearing a bra and a top and going on about your day. Those kinds of big changes are exceedingly rare.

Dr. Shreya Trivedi: Okay, sounds like breast radiation side effects are more on the surface and hammers home a big takeaway, that radiation is not just location-dependent, depth-dependent.

Dr. Matthew Abrams: For breast cancer, the unique situation in the breast is that the breast tissue goes all the way up to the skin surface as to the, as opposed to the prostate, which is much deeper seated inside the pelvis. So what’s different with breast, uh, radiation is that you often see a skin reaction that you do not see with prostate radiation or you don’t normally see with prostate radiation. So if I treat, uh, a breast cancer, you know, you could definitely see a skin reaction, but when I’m treating pancreatic cancer, I, I’ve never seen a patient with a skin reaction or a burn. 

Dr. Shreya Trivedi: So, for patients with deeper visceral tumors, we can tell them that they’re probably not going to have dermatitis.  

Dr. Sam Kumarasena: I love that! That’s actually such a good point. Now That I think about it, I’ve don’t think I’ve ever seen a pancreatic cancer patient with dermatitis.

Dr. Shreya Trivedi: Yeah, same!

Dr. Sam Kumarasena: And you know, reflecting on that, some of these side effects are exceedingly rare, but questions and anxiety about them are very common. And we can help with that! We can help address some of those fears and reassure people.

Dr. Shreya Trivedi: Yeah, no, definitely! And I feel much more empowered to do that after this episode! So let’s loop back to breast cancer. We talked about dermatitis as a short-term side effect, what about the long-term side effects here?

Dr. Daphna Spiegel: Long term things that live near the breast or things like the heart and the lungs and the lymph nodes. And so long term risks have to do with things like developing pneumonitis or lymphedema or, and this is very rare these days, but radiation induced cardiac toxicities, but those are pretty rare with our modern radiation techniques. So possible, but really unusual.

Dr. Shreya Trivedi: So, I think our takeaway here is again the “depth-dependence” of breast radiation. The deeper structures like the heart and lung are generally spared in breast radiation, unlike with lung radiation. So, Sam why don’t you summarize here?

Dr. Sam Kumarasena: Yeah. I think my take aways from breast radiation side effects is that I can counsel my patients to expect sunburn-like dermatitis, or other skin changes. And I will keep symptomatic pneumonitis and cardiotoxicity in mind, but I’ll also remember that those are thankfully both very rare with modern radiation.

Dr. Sam Kumarasena: And the second to last, let’s move on to prostate radiation. What are the acute side effects? We already kind of mentioned that people aren’t really going to see burns with it, so I guess that’s one win! 

Dr. Shreya Trivedi: Yep!

Dr. Daphna Spiegel: A lot of the side effects that you can experience have to do with what’s nearby. And so for a prostate patient I might say, you might find you’re going to the bathroom more frequently, urinating more frequently, sometimes even having more frequent bowel movements or looser stools things like that. 

Dr. Sam Kumarasena: We’re back on that location-dependence theme here! The acute side effects are gonna involve what’s nearby the prostate, the bladder, the rectum, basically anything in the pelvis. Now, how about the late side effects?

Dr. Matthew Abrams: Late side effects. Uh, so things like, um, uh, erectile dysfunction, uh, is a ongoing issue that, uh, can happen after any, um, uh, treatment to the prostate, whether that be surgery or radiation. Sometimes patients, uh, present with, uh, rectal bleeding. That can be associated with the late complication from, from radiation to the prostate. Suffice it to say that if, uh, a patient showed up with prior prostate radiation in your clinic with rectal bleeding, you would absolutely wanna work up that rectal bleeding for any other reason. I would not, um, write it off as related to radiation. That would be almost a diagnosis of exclusion. You would want to rule that up for work that up for, for, you know, as you normally would, um, whether that be, uh, you know, a rectal exam, colonoscopy, et cetera, uh, to make sure you’re not missing any other underlying malignancy, for example.

Dr. Sam Kumarasena: Aye aye, Captain! The diagnosis of exclusion is hammered home yet again. 

Dr. Shreya Trivedi: But, wait a minute, bones are also in the pelvis too, so how does prostate or pelvic radiation affect the bones?

Dr. Daphna Spiegel: Anytime we radiate the pelvis, there’s always the possibility long term that could cause issues with the fracture. Really, it’s true for any bone, but we think about it a lot because obviously you know have really important bones that live in your pelvis. And so we think about that and counsel patients that they may be more likely to develop a hip fracture down the road if they’ve gotten a lot of radiation in this area. 

Dr. Sam Kumarasena: And as a little aside here, I looked into it, to see if there is anything to prevent some of these pelvic fractures and unfortunately, our interventions, things like calcium and vitamin D supplements, or even bisphosphonates, nothings really been shown to be effective in preventing these fractures.

Dr. Shreya Trivedi: Yeah, bummer, it’s surprising given bisphosphonates aren’t, but it’s good to know! So let me try to summarize prostate radiation side effects, big picture ones. Because radiation is often deeper, we are going to see collateral damage to nearby organs, like prostatitis, cystitis and so on. As well as seeing pelvic insufficiency fractures.

Dr. Sam Kumarasena: One last things that came up about prostate radiation side effects, do we see these prostate radiation side effects with all the different types of radiation? This’ll actually be a throwback to part 1, in which we learned that patients with prostate cancer can either get, external beam radiation therapy, OR brachytherapy, with a radioactive source placed at or in the tumor.

Dr. Shreya Trivedi: Yeah so talking to our experts, it turns out BOTH external beam and brachytherapy can produce similar local side effects, think about the cystitis and proctitis that we just talked about. But, because with brachytherapy, the radiation stays closer to the tumor, brachytherapy is going to have a lower risk of affecting organs further away, like the bone. So that means patients getting brachytherapy are going to have a lower risk of pelvic fractures than those getting external beam radiation.

Dr. Shreya Trivedi: Alright, why don’t we finish our episode on early and late side effects with brain radiation. Let’s start off with the short term side effects to look out for?

Dr. Daphna Spiegel: The difficulty with the radiating the brain is sometimes the radiation can cause inflammation and that inflammation can trigger some very specific side effects depending on exactly where the inflammation is. And so the brain is a little bit unique in that way that some of the side effects can manifest as really totally wide range of neurologic symptoms. It can even be a seizure, it can be difficulty with speech. So anything that just seems off could be from the radiation if it’s a neurologic symptom. So that’s a little bit different than most of the other kind of sites. But those things are typically temporary, they get better with time. 

Dr. Shreya Trivedi: Wait, definitely not what I was expecting! Did not expect such a wide range, and even to hear about focal neuro deficits being a radiation side effect. What a plot twist!

Dr. Sam Kumarasena: I know, right! Thing is, with focal neuro deficits, you’re not going to really know whether those focal deficits are due to disease progression, or if it’s just post-radiation. And I think this is where we can loop in our rad oncs to weigh in, on what could potentially be a radiation side effect!

Dr. Daphna Spiegel: Long term toxicity is memory impairment and that’s usually difficulty with short term memory. And so it can become more difficult for patients to remember where they put their keys or remember tasks that need to get done during the day. So we tell patients, make a list or have a place where you need to put your keys and try to find ways to help them.

Dr. Sam Kumarasena: And let’s note here, the significant memory loss Dr. Spiegel is talking about, is extremely common after whole-brain radiation, with over 80% of patients experiencing cognitive impairment. This is less common with SRS, but it still happens, on the order of 30-40%. This difference is because targeted radiation, like SRS, tends to have fewer side effects, as we talked about in Episode 1. 

Dr. Shreya Trivedi: Right, so let me summarize brain radiation side effects. So I was pretty surprised to hear, unlike most of the other sites radiation and possible side effects, those are often diagnosis of exclusion, and it sounds like with radiation to the brain it can lead to such a wide range of symptoms and, of course, it’s a bit hard to know if its from the radiation or if its the disease progressing. And then, unfortunately, it sounds like the long-term side effect with whole brain radiation is going to be cognitive impairment.

Dr. Sam Kumarasena: And with that, that brings us to the end of our part-two series! That was quite the rundown! 

Dr. Shreya Trivedi: Yeah, definitely! And just to add, you know, we talked a lot about radiation side effects here, but we do want to reinforce that often times, radiation is safe, and well-tolerated, in the majority of our patients! 

Dr. Sam Kumarasena: Thanks for joining us on this journey, everybody!

Dr. Shreya Trivedi: And, Sam, thanks for leading us in this journey! I’ve learned a ton. If you found this episode helpful, please share with your team and colleagues and give it a rating on Apple podcasts or whatever podcast app you use! It really does help people find us! Tweet us, leave a comment on our website, or on instagram or facebook page. Thank you to Dr. Sarah Stephens and Dr. Julian Hong for reviewing this episode. Thank you also to Daksh Bhatia for audio editing and to Dr. Kabao Vang for the accompanying graphic. 

Dr. Sam Kumarasena: This episode was made as part of the Digital Education Track at BIDMC. A heartfelt thank you to all our great educators and mentors!

Dr. Shreya Trivedi: As always, we love hearing feedback. Email us at hello@coreimpodcast.com. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.

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