Radiation pneumonitis is defined as inflammation in the lungs following radiation, and it is a common problem we see in patients who have received recent radiation therapy for lung cancer. It typically occurs several weeks or even a few months after radiation has been completed, with symptoms of shortness of breath, cough, and sometimes a fever. Chest x-rays or CT scans show an infiltrate, which is a cloudy area in the lung tissue that looks like pneumonia. It is very hard to determine how commonly it occurs, because 1) the symptoms are often presumed to be due to lung cancer or pneumonia and therefore may not be recognized as being from pneumonitis, 2) people who have the radiologic findings but minimal or no symptoms will not be recognized as having it, and, 3) patients who develop progressive or recurrent cancer may actually decline too quickly to develop it. Overall, the estimates of moderate to severe pneumonitis are in the 5-20% range in most recent studies with full dose radiation alone or radiation with chemotherapy. Although it often resolves, with or without any treatment, severe cases can be fatal.
Several studies have identified clinical variables that may be associated with increased risk of developing radiation pneumonitis. Although some inconsistent results have sometimes identified more advanced age, female sex, active smoking, and worse lung function before treatment as being associated with higher risk for pneumonitis, the clinical factor most commonly reported to be welll associated with increased risk is chemotherapy along with radiation, especially if that chemo is administered concurrently with chest RT. Some agents, such as the taxanes (taxol and taxotere) as well as gemcitabine have been particularly associated with radiation pneumonitis, at least in relatively small studies. But the most important factor that helps to predict risk of developing radiation is the volume of normal lung tissue that receives a certain threshold dose of radiation. For instance, V20 is the volume of lung that receives at lease 20 Gray of radiation, which is enough to lead to permanent damage to lung function. Obviously, radiation oncologists want to minimize the amount of surrounding normal lung that is damaged by radiation without compromising the ability to deliver good coverage for the entire volume of the tumor itself. Some of the newer radiation techniques such as intensity-modulated radiation therapy (IMRT) and 3-dimensional conformal RT may allow radiation oncologists to deliver higher doses to the tumor in a more precise way, therefore minimizing volume of heavily treated surrounding lung and lowering risk of radiation pneumonitis. This hasn’t been carefully studied yet, but the earlier evidence suggests that this may be the case.
There have been some attempts made to prevent radiation pneumonitis in ways other than modifying the radiation treatment plan. For instance, the drug Ethyol (amifostine) was developed as a cell protectant that may reduce the risk of radiation-induced toxicities. Although an early trial suggested a potential reduction in pneumonitis risk in patients who received amifostine during chemo and radiation (abstract here), a subsequent larger phase III randomized trial of chemoradiation with or without amifostine showed no improvement in pneumonitis rate or long-term survival when this agent was added (abstract here). Several other agents are being tested, ranging from the blood pressure medicine class known as ACE inhibitors, to melatonin, to the medication for improving circulation known as pentoxifylline (Trental). None of these has any established role at this point in reducing risk of radiation penumonitis.
Because radiation pneumonitis develops weeks to months after radiation is completed, the cause of the problem can’t be undone once a patient develops clinical symptoms and imaging consistent with pneumonitis. Instead, steroids like decadron and prednisone, which have powerful anti-inflammatory properties, are the most widely used treatment for severe cases, when supportive care such as oxygen and time for slow healing are not sufficient for a patient. Many patients require a very slow taper of steroids over months to improve sufficiently, and some patients remain oxygen-dependent on a chronic basis.
The other practical consideration we encounter with radiation pneumonitis is that it literally clouds the picture of what is happening to the cancer after treatment has been completed. It is very common for patients who have received aggressive chemo and radiation to experience ongoing cough and shortness of breath, along with x-ray or CT findings that show ambiguous changes that could represent post-radiation inflammation or fibrosis, as well as possibly residual/recurrent active cancer. In fact, since inflammation is also PET avid, it is quite possible to have abnormalities on both CT and PET scans after chemoradiation that could represent either post-treatment effects or active cancer, or possibly a combination of these.
Overall, then, it is worth knowing that radiation pneumonitis is a common cause for both lung symptoms and scan abnormalities in the weeks and months that follow radiation, especially if chemotherapy is also given at that time. While sometimes invasive repeat biopsies may be performed to clarify whether residual cancer is present or absent, often repeat scans that demonstrate changes over time are employed. In the absence of further treatment, cancer should become larger and more PET avid over time, while post-treatment effects should be stable or less prominent with ongoing follow-up. Radiation penumonitis remains a significant clinical problem in terms of both symptoms and difficulty interpreting outcomes. While we are still searching for effective drugs to minimize risk of developing pneumonitis, there are also studies now that suggest that newer radiation techniques and a vigilant effort to minimize radiation-induced damage to normal tissue surrounding a tumor are the most effective mechanisms available now to reduce the magnitide of this problem.