Radiation, a mainstay of cancer treatment, begins a fade-out

Every year, doctors get better tools to fight cancer. Engineered cancer-killing cells, immunotherapies, targeted drugs, and more are helping clinicians cure more patients. Increasingly, though, oncologists are trying to use less radiation, long one of the main pillars of cancer therapy. In some cases, they are even keeping certain patients with low-risk tumors off radiation entirely.

“We are in an era of radiation omission or de-escalation,” said Corey Speers, vice chair of radiation oncology at the University Hospitals Seidman Cancer Center and Case Western Reserve University. “Radiation is perhaps one of the most precise and most effective cancer therapies we have, so it will always play an important role in cancer management, but there are situations now on an individual patient basis where radiation may not be needed.”

Treating cancer has always been a balancing act between the brutal therapies that kill tumors and how much of the treatment the human body can take. At their worst, the side effects of chemotherapy, radiation, and surgery can leave lasting damage, disrupt key bodily functions, or permanently disfigure a patient. So doctors have always wondered just how much of a therapy they could dial back without sacrificing any efficacy. That’s been true for medicines and surgery as well, said Abram Recht, a radiation oncologist at Beth Israel Deaconess Medical Center.

“People have been looking at reducing the intensity of surgery, radiation, and systemic therapy for a long time, and there’s always been controversy about it,” Recht said. “The balance has always been the question — is reducing the intensity of treatment going to impact the long-term effectiveness? People didn’t know what to do starting off, so they decided to treat people until they had to stop — until they couldn’t take it anymore.”

It was the work of decades that helped clinicians feel comfortable scaling back chemotherapy or surgery, eventually adopting less dramatic interventions as standard practice. One example is the radical mastectomy, Recht said, where surgeons once removed not only the breast but also the chest wall muscles and nearby lymph nodes in an effort to cut down on breast cancer deaths. It took over a century of experimentation and clinical trials to go from that to the breast sparing procedures surgeons take now.

“When I was starting out in practice as a resident, it was not unusual for women to receive 2 years of chemotherapy after surgery. Almost nobody completed it,” Recht said. “Then a randomized trial in Milan under the auspices of Umberto Veronesi compared 12 months of chemo versus 6 months. And there was no difference.”

Radiation has also gone through a century of advancements, with early cancer radiotherapy beginning shortly after Wilhelm Röntgen discovered X-rays in 1895 and Marie and Pierre Curie discovered radium in 1898. Since then, radiation has evolved into treatments that include modern brachytherapy, inserting a radioactive source into a tumor, and focused beams of ionizing radiation that kill off cells while incurring as little off-target damage as possible. The new thinking about easing back on radiation goes beyond just easing back on the treatment, though. “There’s also been this long history of trying to reduce the morbidity of radiation in different ways, and the big thing that people think about is the best way to reduce morbidity is to not give it at all,” Recht said.

There are more and more settings where that appears to be possible for patients, with studies showing that omitting radiation from standard therapy seems to make little or no difference in outcomes in certain low risk or early-stage disease in lymphoma, breast cancer, thyroid cancer, and more.

There are two main reasons for this. Treatments for cancer today are magnitudes beyond what they were even just two or three decades ago. Also, oncologists have more advanced tools to understand patients’ tumors like better biomarkers or imaging, often allowing them to triage different cancers as low or high risk.

“We can do better surgeries, better supportive care, better chemotherapy, more effective chemotherapy. We have better scans to stage people properly and better molecular tests,” said Michael Cecchini, an oncologist who treats gastrointestinal cancers at the Yale Cancer Center. “That’s when we can start going back to the drawing board and instead of adding on something new to cure more people, asking if we can modify what we’re doing to reduce the toxicity.”

One recent example is in rectal cancer, where modern, effective chemotherapy regimens exist and radiation can cause quite a bit of collateral damage to surrounding organs. “You have to think about where you’re radiating,” Cecchini said. “10 doses to a shoulder, maybe you get some short-lived blood count abnormalities. When we radiate the pelvis for rectal cancer, there are several important organs there. Radiation is very focused, but you hit more than the tumor.”

In the short term, patients who receive pelvic radiation can experience diarrhea and other acute toxicities. In the longer term, these patients are more likely to have urinary incontinence and can run the risk of infertility. A team of researchers at Memorial Sloan Kettering Cancer Center wanted to see if patients with certain rectal tumors that are farther away from the anus might be able to omit radiation and only get chemotherapy. These “higher” tumors tend to be lower risk and have fewer complications.

“The investigators showed by doing this, there was no statistically significant reduction in survival. So if it’s not inferior, why take the extra potential side effects?” Cecchini said. “As an oncologist, I was thrilled. Taking it back to my own practice to think, some of my patients, especially younger patients where fertility may be an issue — if we can be less toxic to them, that’s huge.”

The phasing out of radiation — and the stepping down of cancer treatment in general — is piecemeal by nature, Cecchini said. Advances in oncology tend to happen in a way that’s specific to a certain cancer subtype. “Cancer is a heterogeneous disease. Breast cancer and colon cancer are very different. Within breast cancer, you have three major subtypes. Within that you have certain mutations that have targeted drugs, and some that don’t,” he said. As these subtypes become better defined and new drugs are developed for them, it becomes more feasible to step down treatment in other modalities.

That doesn’t mean there is no role for radiation in the future, even as oncology continues to advance, cancer type by cancer type. But, that role will be smaller, Recht said. “If we can reduce the morbidity of treatment without harming the cure rate, in the long run, people will be better off.”

Radiation is still needed for both curative plans and palliative plans when patients have higher risk tumors or more advanced cancer. In some settings, doctors still want to throw the kitchen sink at a patient with a tough cancer, in the hope that they will live longer, better, or become cancer-free. “Radiation’s role is expanding in patients with metastatic disease, allowing us to cure patients who were previously considered incurable,” pointed out University Hospitals’ Speers.

The use of radiation in more advanced cancer, even as it decreases for earlier cancer, arises in part from advances in radiation therapy as well, including the development of more precise radiotherapy technologies and techniques like proton beam therapy and stereotactic body radiotherapy. “That delivers doses of radiation to tumors in a very safe and very effective fashion without causing damage to surrounding organs,” Speers said.

Or, as Recht put it, there will be work yet for radiation oncologists.

Correction: An earlier version of this article misstated the name of Beth Israel Deaconess Medical Center.