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What Are Late Radiation Side Effects?

May 17, 2022

Radiation is more likely to damage and kill cancer cells than normal cells.  This is really why we can use radiation as a cancer treatment in the first place.  We could spend an entire blog topic discussing why radiation has a much greater effect on cancer cells relative to normal cells.  In fact, there are entire books written on that subject.  While radiation kills more cancer cells than normal cells, radiation nonetheless can have detrimental side effects on normal tissues.  In the most general sense, radiation oncologists divide these normal tissue side effects into acute side effects (for example, those occurring during, or in the days and weeks after radiation) and late side effects (for example, those occurring six months and beyond after radiation).

For any course of radiation therapy, the side effects are typically limited to the area being treated with radiation.  For example, women being treated for breast cancer will typically have the skin at the breast become pinker or darker or drier during the course of radiation.  Men being treated with pelvic radiation for prostate cancer may have increased urinary frequency.  These acute side effects are typically mild and temporary – and are quite common.  Late side effects are much less common, but they can be longer-lasting or even permanent.  Because of this, we worry as much (or more) about late side effects as we do acute side effects.

As an example, take someone who is being treated with radiation for esophageal cancer.  During the course of their radiation, normal esophagus cells may be unable to repair radiation damage and may die off in the process.  This can leave the esophagus without its full lining intact, and patients can feel a sore throat, especially with swallowing.  But soon after radiation, new cells are made to line the esophagus, and the difficulty swallowing resolves.  Some areas of the esophagus, however, may have enough cells die off, that the body will turn that area into a scar.  This scarring process (fibrosis) may occur over months.  In this way, someone may have a sore throat during radiation (acute radiation esophagitis) and someone else may have a sense of food hanging up six months after radiation (late radiation fibrosis).

Several things can lead to late radiation toxicity.  For this part, just know that the unit of radiation given through a course of radiation is described by the standard metric measurement called Gray (abbreviated Gy).  In the most general sense, acute radiation toxicity is more likely related to the total dose of radiation (e.g., 70 Gray over seven weeks may be associated with more acute toxicity than 60 Gray over six weeks).  While late toxicity may be more associated with the radiation dose on any given day (e.g., 4 Gray each day may be associated with more late toxicity than 2 Gray each day).  In other words, acute toxicity is felt to be more related to total dose, while late toxicity is felt to be more related to daily dose.  Planning radiation then is a careful balance between having enough total dose to kill tumor cells without excessive acute toxicity, and completing the radiation in a timely and convenient fashion without excessive late toxicity.

Luckily, we have study after study that has helped us find those balancing points, such that we have good evidence to support picking a daily dose and a total dose that maximizes our chance for controlling the cancer, while minimizing the chance of both acute and late toxicity.  If you have ever wondered how your doctor came up with the radiation dose and the number of treatments for the course of radiation for you or a loved one… this is how.  In all frankness, it’s a little more complicated than this.  We have tables and tables of “dose constraints” for the normal organs we are trying to avoid.  For any given organ, we can estimate the risk of acute and/or late toxicity for any given dose across any specific volume of that organ.  In this way, we can design the X-ray beam angles and sizes and shapes in a way that maximizes our coverage of the target, while respecting the tissue tolerances of the normal tissues.

If you take anything away from this, just know:  for the last hundred years, radiation oncologists have worked very hard to figure out the best dose per day and the best total dose to maximally cover the tumor while minimizing both acute and late toxicity.