Making breast cancer treatment less invasive

Targeted radiation during lumpectomy reduces treatment time for low-risk patients

By Megan Headley

Breast cancer may be painful and invasive, but researchers have worked for years to reduce the physical and emotional toll on women undergoing treatment. Now, women diagnosed with early-stage breast cancer may have a single-day radiation treatment available to them.

Evidence indicates that for patients with low risk and good prognosis, localized treatment with targeted intraoperative radiotherapy (TARGIT) may be equally as effective as standard radiation, with potentially less damage to normal tissues and organs.

Research outlining a TARGIT clinical trial and its results, published in the August 2020 issue of The BMJ, concludes that a single targeted dose of radiation delivered during lumpectomy helped patients finish their radiation treatment the same day as surgery and begin recovery faster. It proved equally effective as postoperative external radiation, which can last several weeks.

“Defeating cancer is not enough. Our jobs must be to find effective therapies that also consider treatment time, side effects, and the overall impact for cancer survivors,” explains Sheldon M. Feldman, MD, who is chief of the division of breast surgery and surgical oncology, director of breast cancer services at the Montefiore Einstein Center for Cancer Care, and professor of surgery at the Albert Einstein College of Medicine. Also a member of the TARGIT Collaborative Group, Feldman says the study “validates intraoperative radiation therapy as a safe, patient-friendly breast cancer treatment and marks a significant step forward in how we can and should be partnering with our patients to help them survive this dreadful disease.”

Steps for reducing treatment time

Dr. Michael Alvarado, a breast surgeon and professor of surgery at the University of California-San Francisco and a co-author of the BMJ research, sees the TARGIT approach as the culmination of decades of work in reducing the time women spend in follow-up radiation after a lumpectomy. While the radiation may be well tolerated, it is also invasive and inconvenient. For standard whole-breast radiation, a patient could need daily 10- to 15-minute treatments, Monday through Friday, for five weeks. That’s time spent in travel to the hospital that takes away from work, caregiving, and life—on top of the fatigue and soreness that comes with radiation.

We’ve already seen some scientific progress on this front. With the advent of a therapy known as hypofractionation, radiation treatment could be reduced from five to three weeks. From there, experts have examined strategies for moving to partial-breast radiation, focusing solely on the tumor-infected area. Doing so would decrease risks associated with whole-breast radiation, including small likelihood of cardiomyopathy, secondary cancers, and other side effects due to radiation scatter. These more targeted approaches shorten the timeline to only five days of treatment, twice a day.

However, nearly 20 years ago, a group of researchers at the University College London began examining whether it might be effective to offer some patients a single dose of targeted radiation during the lumpectomy, eliminating the need for follow-up radiation altogether. This conjecture from professors Jayant Vaidya, Michael Baum, and Jeffrey Tobias was the genesis of intraoperative radiation therapy (IORT)—which is what TARGIT delivers.

Alvarado explains, “The question was, could you give one dose and have that be equivalent to other types of radiation?”

Tests of this approach have all utilized the Intrabeam® device made by Carl Zeiss. Though the study design randomized patients to receive either TARGIT or standard whole-breast radiotherapy, researchers also took a risk-adaptive approach: If a TARGIT patient was revealed to have a higher risk at the final pathology report than assessed at the original pathology, they were also given whole-breast radiation. In essence, the TARGIT served as the first “boost” of radiation for higher-risk patients.

“It wasn’t truly randomizing one dose in the OR versus standard radiation,” Alvarado says. “It was a risk-adaptive approach where you get a one-time dose and some people might get additional radiation.”

Since the start of this research in 1998, more than 40,000 patients have been treated in 350 breast cancer centers in 10 countries using the TARGIT method. Alvarado’s team at UCSF became the first institution in the United States to utilize this approach in 2005. Data remained promising throughout this research period. As the BMJ study indicates, the risk of a local recurrence at five-year follow-up was 2.11% for TARGIT, compared to 0.95% for external beam radiotherapy—a difference of about 1%. There was no statistically significant difference in survival between either method.

During this time, researchers also tracked the level at which women were willing to accept a low increased risk of local recurrence with no difference in survival for the convenience of having a one-time dose of radiation. The patient preference trial found about 70% of women would make that tradeoff. The average amount of risk that women would accept was about 2.5%, indicating a strong preference for a solution of this type.

And while Alvarado says, “I don’t know that we can hang our hat on it just yet,” there is also an indication that the TARGIT approach offers a statistically significant reduction in the number of cardiovascular deaths compared to standard radiation. “As breast cancer treatment gets better and better and more women are surviving breast cancer, there are these other competing risks from the treatment that we do,” he adds.

The next steps for TARGIT

Alvarado sees the TARGIT approach as “one of the most impactful trials for locoregional treatment of breast cancer in 20-plus years.” Yet despite decades of research, there are still hurdles to overcome to broaden acceptance of this treatment.

“It’s a paradigm shift, to be able to give one dose in the OR compared to smaller doses over time,” Alvarado says. However, while from his perspective it’s often easy for physicians to add new treatments to address illness, it’s much harder for them to accept the idea of lessening treatment. “Most physicians tend to be very conservative about withholding treatment, even with data that shows that it’s OK.”

He points to data on the Oncotype DX Breast Cancer Assay as an indicator. “They’ve had data for 15 years showing that women are overtreated with chemotherapy,” he says. “The data was exceptionally good in 2006. It was really great in 2010. It was really good in 2016. And people were still getting chemotherapy when they didn’t need to.”

There’s another aspect Alvarado says may sway adoption. “This procedure doesn’t reimburse very well,” he says. “Surgeons who do this don’t really get anything for taking the extra 40 minutes in the operating room to do the biology. Radiation oncologists can actually bill less for the one-time dose. No one likes to say that out loud, but that does play into it.” That said, health systems focused on patient experience may value the care improvements much more highly.

Now, Alvarado says, the TARGIT researchers are reaching out to the American Society for Radiation Oncology and the American Society of Breast Surgeons to broaden both awareness and guidelines.

“It’s going to take both physician advocates for this as well as patient advocates,” he says. “We’re not asking that it becomes the standard of care, but it should be allowed in the discussion with the patient, so the doctor and patient can make their best decision for treatment.”

Megan Headley is a freelance writer and owner of ClearStory Publications. She has covered healthcare safety and operations for numerous publications. Headley can be reached at megan@clearstorypublications.com.