Higher-dose Stereotactic Radiotherapy Achieves Better Control for Many Aggressive Lung Tumors

Treatment decision must be balanced against toxicity concerns

Stereotactic body radiotherapy (SBRT) made it possible to treat lung cancer patients with high doses of radiation in as few as one to five sessions. But do patients do better with five sessions, or three? And can clinicians really achieve tumor control with a single session? A large study by Cleveland Clinic physicians offers new guidance.

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The retrospective study presented at the annual meeting for the American Society for Radiation Oncology found that lung tumors that were larger or more aggressive benefitted more from higher-dose radiation over fewer sessions. Notably, the researchers also found that a single high-dose session was as effective in achieving control as other regimens.

While generally quite safe, these regimens can occasionally be  associated with greater toxicity for certain tumor locations, especially in a patient population that is often frail. With that in mind, clinicians need to use their own judgment in balancing tumor control with a treatment plan the patient can tolerate.

“In general, we would like to dose-escalate these patients to the higher-dose/fewer fraction regimens,” says first author Kevin Stephans, MD, a radiation oncologist at Cleveland Clinic. “However, we still have to be mindful of creating toxicity in vulnerable patients.”

Study design

For the study, researchers identified 1,573 patients who received stereotactic radiotherapy for inoperable stage 1 non-small cell lung cancer between 2003 and 2020. They looked at risk factors that affected treatment outcomes, including tumor size, PET avidity and type, and compared results of patients who received five, three or one treatment fractions or sessions. 

The study builds on two prior randomized trials that looked at smaller groups of approximately 90 patients. Those studies suggested that outcomes were similar across the different treatment regimens. Stephans said his team wanted to investigate whether a larger data set might reveal nuances that weren’t apparent in the previous research.

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Importantly, the retrospective study also includes data on patients with larger tumors than were considered in the previous studies. “Most of the data that’s out there is really for tiny tumors, so not only do we have larger numbers, but there’s also a bigger range of tumor sizes,” he says.

Study results

The results found that most patients do very well with SBRT, and treatment is generally very successful. However, factors associated with tumor recurrence included tumors that were larger, brighter on PET scans and had squamous cell histology.

“For favorable tumors, like a small adenocarcinoma that’s not too bright on PET, you get great control no matter what you use,” says Dr. Stephans. “However, our main finding is that for those slightly harder-to-kill tumors, it seems like the higher dose regimens are more successful, and that’s the single-fraction or the three-fraction regimens.” In practice, however, many patients are recommended for SBRT because they are too sick or frail to undergo surgery, and enter treatment with significant comorbidities. Depending upon tumor location these patients may not be eligible for higher doses of radiation and require classic 5 fraction schedules.

“Some patients are so frail that the goal is to use the least toxic regimen, no matter what, and you can accept good control,” he said. “For other patients who are closer to the side of tolerating surgery, you might want to be fully aggressive.”

Evidence of single-fraction treatment efficacy

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The single-fraction regimen still hasn’t been widely adopted, perhaps because clinicians still haven’t accepted the idea of attacking cancer with a single treatment. However, the study adds to previous research showing single-fraction treatment is a viable option.

“The single-fraction regimen certainly performs as well as any regimen out there,” says Dr. Stephans. That is significant because, in addition to offering good tumor control, single-fraction treatment is also more cost effective and reduces potential exposure to COVID-19 in the hospital for vulnerable patients.

Next steps

Based on these results, researchers are working on developing a model that would use both patient risk factors and tumor genetic markers to predict the best regimen for tumor control. “You can put that all together to get a model that gives you more information about how to individualize treatment for each patient,” Dr. Stephans says.