Targeted Treatment and Improved Radiation Technologies Offer Advantages in CRC Realm

Yufei Liu, MD, PhD

Although there are rising incidences of colorectal cancer (CRC) within the United States and globally, evolving radiation strategies and technologies, such as stereotactic body radiation therapy (SBRT) and intensity modulated radiation therapy (IMRT), have providing more targeted treatment to patients within this population, according to Yufei Liu, MD, PhD.

“Increasingly, we've seen that CRC most commonly affects people who are over the age of 50, but recently, we found that it affects a lot of young people as well,” Liu explained during an interview with OncLive® during CRC Awareness Month, which is observed annually in March. “An example is actor Chadwick Boseman. We see that even very healthy, young people can be affected by CRC; therefore, it's important to spread that awareness and better understand how we can discover CRC [earlier] and how we can treat it more effectively.”

In the interview, Liu discussed current radiation strategies utilizing SBRT and IMRT; patient populations eligible for radiation therapy; helpful biomarkers used to tailor treatment options; and existing challenges in implementing precision medicine in CRC.

Liu is an assistant clinical professor in the Department of Radiation Oncology at City of Hope in Duarte, California.

OncLive: How have developments in radiation strategies such as SBRT and IMRT shaped treatment options in CRC. What are some advantages of these strategies?

Liu: Radiation evolves a lot with technology, so when you think about how much technology has evolved in the past few decades, it gives you an idea of how much radiation has come along during that time. Traditionally, with radiation, in the very beginning, radiation [was planned via] X-ray guidance, so we would see the part of the body that we're treating using X-rays, and then we would deliver radiation to that large area to encompass the tumor and make sure that we don't miss what we're trying to treat.

Nowadays, we use both CT guidance and, increasingly, MRI guidance in designing our radiation plans, and that, coupled with technology such as SBRT and IMRT allows us to shape the radiation dose a lot more precisely. Therefore, instead of covering a very large area, now we can shape the radiation field more precisely, while at the same time, we're sparing normal organs from radiation, such as the bladder and the intestines.

When it comes to SBRT, the biggest advantage is that it allows for a very highly conformal radiation dose. That means that we can give a very high dose to where the tumor is located, and at the same time, the dose rapidly falls off once we go away from the tumor. That allows us to protect normal tissue from the effects of radiation.

What patient population benefits the most from radiation therapy?

Radiation can be beneficial in a lot of different patient populations. For CRC, we generally divide it into colon cancer vs rectal cancer. For rectal cancer, radiation is part of the mainstay of treatment for locally advanced disease, so it's used in combination with chemotherapy and surgery to offer a curative option for patients. In the context of colon cancer, radiation is used for patients who cannot tolerate surgery or are not good surgical candidates. It can be used with chemotherapy to provide a curative approach.

Additionally, we've come to realize that even in metastatic CRC with limited sites of metastases, such as to the lung or the liver, treating these other sites aggressively with radiation as well can help improve treatment outcomes. Therefore, another area where radiation has been used is to target metastatic sites of disease. The other use of radiation is in patients with advanced cancers who are having metastases-related pain. For example, if patients have bone and muscle metastases, radiation can be used to help provide pain relief in those situations.

What are some specific biomarkers that have recently been crucial in treatment selection within CRC?

One of the most exciting biomarkers we use is related to mismatch repair [MMR] proteins; that's one of the key things we use to guide treatment selection regarding immunotherapy. We know that various cancers develop because of mutations that occur in certain pathways. One of these pathways is known as the MMR pathway. It's a pathway that ensures that during DNA replication, the DNA is faithfully replicated. In some [patients with] CRC, that pathway has a significant number of mutations. What we found is that when we look to find patients with deficiencies in that pathway, there are patients who benefit greatly from immunotherapy. Sometimes, these patients can get immunotherapy without even receiving radiation, chemotherapy, or surgery. So that's been one of the most exciting biomarkers that we've had recently.

What are some challenges in implementing precision medicine in CRC in clinical practice?

When it comes to precision medicine, [we need to do] the relevant testing, [meaning] testing for MMR [status]. Certainly, at large academic centers, it's something that is more routinely done. However, it's something that we would like to implement more in all practices, specifically to do their MMR testing and testing for other potential targetable mutations, such as KRAS mutations. That's one important challenge: do the testing at the time of diagnosis to guide optimal treatment. Another approach, from the radiation standpoint, would be technology and having the latest technology using the IMRT and SBRT techniques to provide optimal organ sparing for patients.