Josh Friedman
2026-01-21 19:30:00
January 21, 2026
6 min read
Key takeaways:
- The number of facilities prescribing single-fraction lung SBRT is gradually growing, yet primarily at high-volume centers.
- Nearly 99% of patients are treated with multiple fractions.
Significantly more facilities prescribe single-fraction stereotactic body radiation therapy than they did 20 years ago, but a minimal number of individuals with non-small cell lung cancer actually receive it.
A retrospective analysis of more than 83,000 patients prescribed SBRT between 2006 and 2021 showed nearly 99% received multifraction treatment, compared with just over 1% who received single-fraction.
Data derived from Moghanaki D, et al. JCO Oncol Pract. 2025;doi:10.1200/OP-25-00826.
Drew Moghanaki, MD, MPH
“Most radiation oncologists I know are deeply concerned about delivering lung SBRT in a single fraction,” Drew Moghanaki, MD, MPH, FASTRO professor and chief of thoracic oncology in the department of radiation oncology at UCLA Health, told Healio. “Most simply have never adopted this.”
‘They think it’s more harmful’
Prior studies have shown single-fraction SBRT for early-stage NSCLC could provide similar tumor control, survival and safety as multifraction treatment, according to study background.
In the randomized phase 2 RTOG 0915 trial, 2.6% of patients in the single-fraction arm developed grade 3 or worse adverse events after a median follow-up of 4 years, compared with 11.1% who received multifraction.
“There was another phase 2 randomized trial at Roswell Park,” Moghanaki said. “They compared one vs. three fractions. They enrolled 94 patients from 2008 to 2015, and with a follow-up time of 54 months, there were no measurable differences in grade 3 adverse events, local control, disease-free survival or overall survival.
“Just a few years ago, Cleveland Clinic, which has been delivering single-fraction for a very long time, reported a 10-year update with one-fraction SBRT. They reported the outcomes of 229 patients. With a median follow-up time of over 30 months, their measured grade 3 event rate was only 0.9%, and they had no grade 4 or grade 5 adverse events. Their cancer outcomes were also similar to multifraction.”
However, Moghanaki still sees a lot of “trepidation” in using single-fraction SBRT.
“Some of my colleagues truly believe it’s more harmful,” he said of other clinicians.
Moghanaki referenced the “old days,” when radiologists delivered single-fraction with large fields that could damage surrounding tissue and organs.
“We now can put that entire treatment prescription into the tumor itself, with just a little bit of margin around it,” he said. “It’s primarily a historical concern that the full prescription would be too much to give at one time.”
Moghanaki also shared that a preference for giving multifraction SBRT is based on decades-old preclinical data that demonstrated it increased safety when larger fields were treated, allowing normal tissues to heal better.
“There’s a new way that we have started to think about how radiation safety might play out,” Moghanaki said regarding whether single-fraction lung SBRT might be a better option. “Each time we deliver an SBRT prescription, the treatment is wounding part of the normal tissue around it. It actually seems that maybe it’s better to wound the normal tissue only once instead of multiple times.”
Moghanaki and colleagues investigated whether their observations on implementation could be seen in data within the National Cancer Database.
Their cohort included 83,377 patients with stage I NSCLC who received either single-fraction or multifraction SBRT between 2006 and 2021.
Numbers ‘blew me away’
In all, only 937 patients received single-fraction SBRT (1.1%; median age, 74 years; interquartile range, 67-80; 53% women; 86% white) compared with 82,440 who received multifraction (98.9%; median age, 74 years; interquartile range; 68-80; 53% women; 88% white).
Researchers did observe a significant increase in usage between 2006 and 2021 (0% to 1.6%; P
The number of institutions and practices that prescribed single-fraction SBRT significantly increased from 2006 to 2021 (0% vs. 11%; P
“I would hope that by today at least 50% of all clinics in this country should be offering single-fraction,” Moghanaki said. “Yet, the low numbers blew me away.”
Facility usage rates increased based on case volume (less than 10 patients per year = 6%; 10-19 patients = 25%; 20-29 patients = 41%; 30 or more patients = 69%).
Factors associated with more utilization of single-fraction SBRT included treatment at academic centers (adjusted OR = 4.64; 95% CI, 3.72-5.8), high-volume facilities (aOR = 10.19; 95% CI, 8.16-12.73) and year of diagnosis (aOR = 1.17; 95% CI, 1.14-1.2).
“I was pleasantly surprised to see that the soaring uptake of single-fraction lung SBRT is occurring in high-volume centers, which tells me that when a place has sufficient resources, they’re sufficiently comfortable and they’re delivering a lot of treatments, that they’re OK delivering all [of the treatment] in one fraction,” Moghanaki said.
Patients who received single-fraction SBRT had a similar OS (median, 3.6 years) compared with those who received multifraction (median, 3.7 years).
Researchers acknowledged study limitations, including lack of data on local control, lung-cancer specific mortality, treatment-related adverse events, SBRT dosimetry and tumor location.
“Currently, our preference at UCLA is single-fraction for all patients with stage I lung cancer, unless there’s some concern about the tumor location where we feel more comfortable delivering a lower dose each day and prescribe it in five treatments,” Moghanaki said. “We’ve had excellent results thus far, and I honestly believe our patients have even less side effects than before with the single fraction treatment as supported by previously published phase 2 randomized data. In fact, many of my patients report no side effects at all. Coughing or pneumonitis seems almost absent with single-fraction. I just don’t see it.”
“There is a lingering concern that the amount of treatment delivered in a single fraction might not be enough to fully eradicate the tumor as well as multiple fractions can, but there are no reliable data to support that concern and we really need to complete a phase 3 randomized trial to assess whether that’s true,” he added.
‘A big believer’
For the past 15-plus years, Moghanaki has been waiting for the RTOG/NRG Oncology group to conduct a phase 3 trial evaluating single-fraction vs. multifraction SBRT.
“I found out that RTOG actually approved a phase 3 trial, back in 2013” he said. “That was going to be the successor from the RTOG 0915 trial, but it was never actually funded.”
Moghanaki and colleagues recently filed a funding application with Veterans Affairs Office of Research and Development to perform their own phase 3 study and are waiting for funding.
“I’ve become a big believer and I want to push single-fraction forward into the future of lung SBRT,” Moghanaki, also the co-chair of the phase 3 VALOR study that randomly assigned patients with operable stage I NSCLC to surgery or SBRT, said.
“I think it’s the way to go that will make treatment for early-stage lung cancer even simpler. There’s another fun fact: It’s only a 10-minute treatment. Our patients lay on the table, the machine does its thing for 10 minutes, and they can go on with the rest of their day as if they never had lung cancer. No anesthesia. No needles. No puncturing of the lungs. No chest tubes. No operation. It’s the quickest, safest treatment there is, and in my opinion almost seems too good to be true.”
“I am hopeful we get funding to run the phase 3 study as the data would not only affirm whether it’s safer, but it would also assure everyone that it has the same efficacy as far as tumor control. Our VA study proposal will measure both of those as co-primary endpoints.”
People have already told Moghanaki that single-fraction would have to show improvement in outcomes to change prescribing habits, though.
“I already have heard from skeptics,” he said. “Let’s say it shows no difference. People will still give multiple fractions because it might generate more revenue. It’s sad, but true. I also think the reason we’re still here, more than a decade after the phase 2 trials were done, is because there’s not a lot of funding for lung cancer research in general, let alone for something like this, where the implementation of single-fraction schedules might provide only an incrementally better advantage for patients, and not necessarily a big home run like new drug discoveries for metastatic disease that has a much higher fatality rate.
“I truly believe we need to finally complete this phase 3 study. The study is designed to show whether single-fraction is the better treatment. If it is better, then it becomes a new standard of care. I think there’s a 50-50 chance it’ll prove to be better, but to know that, we need to run the study.”
For more information:
Drew Moghanaki, MD, MPH, FASTRO can be reached at [email protected].
Sources/Disclosures
Source:
Moghanaki D, et al. JCO Oncol Pract. 2025;doi:10.1200/OP-25-00826.
Reference:
Disclosures:
Moghanaki reports leadership with LungLife AI and Respirati; stock and other ownership interests in Auratera, LungLife AI and Respirati; honoraria from AstraZeneca and Varian Medical Systems; consulting or advisory roles with AstraZeneca; research funding from Bristol Myers Squibb Foundation; and travel, accommodations and expenses from AstraZeneca and ViewRay. Please see the study for all other authors’ relevant financial disclosures.
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