Recognizing the Value of Radiation Therapy in Lung Cancer

Radiation has proved to be an integral modality in the treatment of patients with early-stage lung cancer, according to Randy Stevens, MD, who added that with mastered delivery techniques and toxicity management, the modality has the potential to move the needle even further in the stage III and oligometastatic settings.

“Now, we’re asking whether giving an experimental immunotherapy with chemoradiation and after chemoradiation further improves [outcomes] compared with giving immunotherapy after [chemoradiation in patients with stage III disease,” said Stevens. “[In the oligometastatic setting,] if everything else is controlled, we might use SBRT [stereotactic body radiation therapy] to try and ablate the few sites of metastases and give patients a much longer disease-free survival [DFS], or [get them to a place where they might] not need to start chemotherapy.”

In an interview with OncLive^®, Stevens, director of Radiation Oncology at White Plains Hospital Center for Cancer Care, discussed the growing role for radiation in lung cancer, delivery techniques, and adverse effect (AE) management strategies.

OncLive^®: When should radiation oncologists be brought into the care of a patient with early-stage lung cancer?

Stevens: It can be one of two places. We have a multidisciplinary lung conference every Friday morning, and at that conference, our thoracic surgeons, lung specialists, radiation oncologists, medical oncologists, and pathologists [are all there]. [At that conference], we look at all the scans the radiologists show them. Our clinical trials specialists and lung cancer navigator [is also in attendance], so that is a very common way I get brought in. When a case is presented, we decide together what the best management is, and then they’ll ask, “When can you see this patient?”

Sometimes though, [the referral] can come from the oncologist. It’s possible that it comes from the oncologist not the surgeon, especially if the patient might not be a surgical candidate. Many times, in early lung cancer, we have to decide what’s right: surgery or radiation? What does the patient’s lung function like? Have they had prior surgeries? Are they on oxygen? That’s our thought process because surgery is still the gold standard, but radiation has a lot of advantages now that we can pinpoint things so well. [Radiation also] doesn’t require surgery, anesthesia, or removal of part of the lung. For many patients, it’s ideal.

Then we have another group that’s very unusual for us. We have a group where sometimes it’s too dangerous to even biopsy them. Maybe they have such fragile lungs that if there’s a small complication with a biopsy that can happen in a small percentage of patients—depending on where the tumor is, sometimes if it looks so obvious on a scan, and it’s growing, or it’s hot on a PET scan—we may actually offer them treatment without a biopsy. In the past, we never did this, but we have so many good diagnostic tools that AEs of radiation, especially SBRT, have gotten so reduced that sometimes it’s safer to treat than to biopsy. That is a new world for us.

Some of these people who are at risk for one cancer can get multiple cancers. [Patients] can get one [cancer], and we follow them, and 3 or 4 years later, maybe they get another small [cancer], and then they get another small [cancer]. You can imagine what would happen if you kept taking pieces of people’s lung out. With radiation, if you find [lesions] when they’re small, you [can] treat a very small amount of lung, and you can continue to offer curative therapy, even though people might have 3 and 4 cancers and been treated multiple times before. In that case, I already know the patient, and I’m following the patient, and I may [have been] the first one to find [the cancer]. Our [multidisciplinary] conference is one of the most common ways we get involved.

How do these techniques and dosing strategies vary for patients with early-stage lung cancer?

[For stage I disease,] the most common [approach] we use right now is SBRT, which is a very precisely focused beam that can be aimed from various angles, but we usually don’t do that. [Instead], we pick and choose the angles that are the best and the safest for the location of the tumor. We make a body mold and immobilization device so each day, patients fall into the exact right position. Those patients may receive 3, 4, or 5 treatments, usually delivered every other day. There’s preparation and setup, but patients are in the treatment room under 15 minutes, sometimes 30 minutes.

Stage II isn’t as relevant to what we do. Though, it can be.

For stage III disease, we do something diametrically opposed, and we usually give chemotherapy and radiation therapy together once a day, 5 days a week for 6 weeks. It’s a very different strategy [compared with stage I disease]. Stage III disease means that often patients have lymph nodes involved, so we’re treating the lymph nodes as well as the primary site of the tumor. It’s a bigger area. It’s 2 different modalities that are not only logistically different, but [have] very different AEs as well.

Could you elaborate on what some of those differences in AEs are?

For SBRT, we’re treating a very small area, and the patient is in a body mold. One of the most common AEs, especially for some of our older patients, is shoulder soreness, because they’re lying down, and their arms are [above their head]. Take a 75- or 80-year-old person who doesn’t exercise a lot because they have lung disease and keep their shoulders up for 30 or 45 minutes for the planning session. [That AE] is not due to the radiation, but rather the treatment position. Patients don’t get that much [toxicity] from the radiation. They frequently get some fatigue after they finish the entire course of treatment, and they may have some shortness of breath. Pneumonitis and inflammation of the lung happens very infrequently with SBRT. [SBRT] doesn’t have a lot of AEs because it’s so localized and precise. There can be more unique AEs, depending on where the specific tumor is.

For stage III disease, we’re treating a bigger area and giving chemotherapy at the same time. We’re also usually overlapping lymph nodes. When we're overlapping lymph nodes, they’re frequently in the central chest area, so for those patients that can get tired, their blood counts can go down because of the chemotherapy, they can get a little short of breath, especially if their blood counts go down. It’s not always the radiation. Sometimes it’s a general weakening.

One of the bigger AEs we see is esophagitis, where the esophagus or the food tube that sits near a lot of these lymph nodes can get irritated. People can get a sore throat; they can say that it hurts or is difficult to swallow. We spend a lot of time discussing with patients ahead of time, their nutrition, their hydration, and the pain and inability to swallow. The nice thing about the treatment is the esophagus recovers quite well. After we’re finished, they may have some changes from the treatment, but the AE profile [of radiation] is so much less than it used to be, because we have so much more sophisticated techniques, and also aggressive early preemptive management of any of these expected [treatment-related] AEs.

How has the approval of osimertinib (Tagrisso) in the adjuvant setting affected the use of radiation in the stage III setting?

We’re doing a lot of clinical trials, and osimertinib is only one [agent]. Newer and more generations [of drugs are] coming. In the adjuvant setting, we’re still giving, unless you’re in a clinical trial, standard therapy, whether that’s surgery or chemotherapy. Now, we may give osimertinib if the patient has an EGFR mutation, and it might in many instances replace chemotherapy as our first choice. [Osimertinib] doesn’t affect radiation as much right now.

In the old days, we used to radiate and give postoperative mediastinal radiation if somebody had an involved lymph node. Nowadays, if we know that the patient has a mutation, [we might try to find a targeted therapy for them instead]. We participated in the ALCHEMIST trial, which is looking specifically at patients with actionable mutations and how to use these targeted agents in the adjuvant setting in patients with stage Ib to IVa disease, where the targeted agents were being saved, when this trial started, for metastatic disease.

Is there a consensus regarding the utility of radiation in the stage IV setting?

Our multidisciplinary thoracic oncology conference is the perfect opportunity to get everybody together and decide, for stage IV disease, which modality we use at which point in time.

Radiation in stage IV disease can be used in 2 ways. It can be used in the palliative setting for pain control, or metastatic disease, where it’s either going to cause pain or an orthopedic or neurologic problem.

Patients with oligometastatic disease might have only 1 or 2 sites of metastatic disease. [The potential use of radiation therapy for patients with oligometastatic disease has] been extremely exciting. Before, patients with a solitary bone lesion or a solitary brain lesion were treated for incurable stage IV disease. Now, some of our patients with stage IV disease, between our targeted agents and some of our radiation techniques, are seen as having chronic illnesses where we’re able to change the course of their lives. [We’re seeing that] patients are living longer with quality of life.

Is there robust evidence to support the use of radiation for patients with oligometastatic disease?

That’s one of the biggest peer-to-peer and insurance questions we get. Where does it cross between evidence based and accepted? The NRG Radiation Oncology Group has looked at a lot of phase 2 data in oligometastatic disease to see if there is a survival and DFS benefit with radiation.

What are some of the strategies that are used to manage radiation induced AEs?

The most important management [tool] is support for your patient. [You want to] be on top of [your patient] to catch things ahead of time. [That also extends to] your nurse practitioner, your nurse, and your team. Radiation oncologists typically see their patients once a week. If you know there may be an impending effect like this, you may want to see your patients more often while they’re coming every day for treatment. If you stay on top [of things] and give them strategies from the very beginning [they’ll be better off]. Tell them, “If and when you start to have trouble swallowing, switch to these foods. They [can then] meet with the nutritionist or the dietician. They [need to] know that we’re there every day if they have a question, and that they don’t have to wait until it’s a big problem. Keeping the patient well hydrated [is also important], whether it’s helping to remind them to drink on their own or having hydration in the infusion center.

There are slurries, and there are over the counter products. We use Magic mouthwash that may be a combination of Benadryl [diphenhydramine] and viscous lidocaine. Some of them use nystatin, and some use Mylanta, but [we have] all kinds of medicines before we get to real pain medicines. To help people swallow, we have little tricks that may sound silly [but help]. Coating [the throat] with a tablespoon or a teaspoon of olive oil before patients eat [helps]. Think about it like a water slide so that the food won’t stick as much and gets down easier.

Numbing the throat for about 15 minutes so patients can get their meals and their nutrition down [is also an option]. Eating protein rich foods [is also recommended] as is avoiding foods that may be very uncomfortable when you have, if you can imagine, a sunburn of your esophagus. [This involves] avoiding spicy, very hot temperature, very acidic foods, and making sure we’re always reinforcing calorie rich [foods].

We also have to alert patients, should they ever feel dizzy, not to wait until they can’t stand up but to alert us when these things are just starting—so that maybe with a little bit of hydration, we end up keeping them out of the hospital.

The other thing we find is when their blood counts go down a little bit, a lot of these AEs flare up, so when a patient all of a sudden is starting to have an AE, you know to check their blood counts to make sure that’s not a contributing factor. Look for thrush or a possible yeast infection, especially in our diabetics because that can cause pain on swallowing. However, if you can keep people well hydrated, with good nutrition, we have a much better time keeping them out of the hospital and avoiding all kinds of AEs.

When you’re lucky enough to have an infusion center like we have at White Plains Hospital, and the chemotherapy floor is 2 floors above me and I sense that the patient might need a little support, I’m able to call upstairs and have the patient go right up and get a little bit of hydration and not take too much more of their time to avoid a bigger problem a week from now. It’s really a luxury to have a center like this with the chemotherapy and the radiation [center] all together in one place where people can go back and forth so easily.

Are there any ongoing or planned studies evaluating radiation therapy that you would like to call attention to?

There are many, and some of them are not just evaluating radiation. Some of the most exciting studies are evaluating immunotherapy with radiation therapy. We have 2 exciting studies that just opened. One is evaluating SBRT with durvalumab [Imfinzi]. There, we’re asking whether a patient with a T1 or T2 non–small cell lung cancer getting SBRT [can experience] improved survival and a reduction in the risk of distant metastatic disease with the addition of durvalumab. We have a lot of patients who we think are going to [be eligible for] that study.

Based on the PACIFIC trial for stage III disease, concurrent chemotherapy and radiation therapy are standard followed by durvalumab. That approach has been shown to improve survival in stage III patients compared with chemotherapy and radiation alone. The second study is [enrolling] patients with stage III disease, and we’re looking at next-generation immunotherapy [in combination with chemoradiation and following chemoradiation].

Is there anything else you want to emphasize regarding the care of patients with lung cancer?

One of your best ways to succeed in your treatment is support, whether it’s transportation, help with meals, or psychological support. COVID-19 [coronavirus disease 2019] has been a very trying time for patients because we have had to limit who can come into the infusion center with them. We have iPads we use to call and facetime family members. We have a secure portal for consults to try and keep everybody involved so that our patients have the best chance of getting through treatment uninterrupted and with as few AEs as possible. COVID-19 has been a particular challenge that hopefully all people who care for the patients, not just the physicians are mindful of to realize how important these supportive issues are to allowing the medical issues to [be taken care of].