Individualized SABR for Lung Tumors Yields Low Recurrence Rates

Individualizing stereotactic ablative radiotherapy (SABR) dose and fractionation according to tumor size, location, and histological characteristics was associated with "excellent" local control and low rates of severe toxic effects in treating lung tumors in a single-arm phase II trial.

The approach achieved 1-year freedom from local recurrence rates ranging from 94% to 97%, with a severe toxicity rate of about 5%, reported Maximilian Diehn, MD, PhD, of the Stanford University School of Medicine in Palo Alto, California, and colleagues.

"To our knowledge, this is the largest reported prospective trial using SABR for lung tumors, and it supports the use of SABR for a variety of scenarios and tumor sizes and for both central and peripheral tumors," Diehn and colleagues wrote in JAMA Oncology.

In a commentary accompanying the study, Vivek Verma, MD, of the University of Texas MD Anderson Cancer Center in Houston, said this individualized strategy not only achieved high local control and low toxic effects, "but also provides high-quality support for patients undergoing lung SABR to receive individualized dose/fractionation regimens based on tumor volume, location, and histology."

The authors explained that, "despite toxic effects from higher dose regimens, there has been concern about lowering the dose due to reports of high local recurrence risk from lower doses, with a threshold of a 100 Gy biologically effective dose (BED) with α/β = 10 (BED₁₀) cited."

In this trial, Diehn and colleagues hypothesized that they could thread the needle on local control and toxicity by prospectively individualizing lung SABR dose and fractionation based on tumor size, location, and histological characteristics -- including the use of lower-dose regimens with BED₁₀ less than 100 Gy for small tumors.

The study included a total of 217 unique patients (median age 72 years, 69% current or former smokers) with 285 treated tumors. They were assigned to three groups according to cancer type: 79 patients with an initial diagnosis of non-small cell lung cancer (group 1), 67 with new or multiple lung cancers (group 2), and 71 with lung metastases or other solid tumors (group 3).

Up to four tumors per patient were treated with once-daily SABR. The dose ranged from 25 Gy in one fraction for peripheral tumors with a volume of 0-10 cm³ to 60 Gy in eight fractions for central tumors with a volume greater than 30 cm³. The most common dose was 25 Gy in one fraction (158 tumors), which was used for small peripheral noncolorectal tumors, with higher doses used for larger tumors or colorectal metastases.

The median follow-up period was 33 months, and the median overall survival was 59 months.

Freedom from local recurrence at 1 year was 97% (90% CI 91-99) for group 1, 94% (90% CI 87-97) for group 2, and 96% (90% CI 89-98) for group 3.

Freedom from local recurrence at 2 years ranged from 90% in group 1 to 95% in group 3; at 5 years it ranged from 83% in group 1 to 93% in group 2.

There were 26 local recurrences. The cumulative incidence of tumor-treated recurrence for the whole cohort was 3% at 1 year, 5% at 2 years, and 7% at 5 years.

Regarding toxic effects, the rate of grade ≥2 pneumonitis was 7%, while grade ≥3 pneumonitis occurred in 1%. Of the 10 patients (5%) with grade ≥3 toxic effects, one death possibly related to radiotherapy occurred (a pulmonary hemorrhage).

Diehn and his colleagues acknowledged several limitations to the study, including the fact that it lacked a uniform dosing control group.

"It is therefore not possible to directly compare the outcomes of our individualized strategy with a uniform dosing approach," they wrote. "Nevertheless, the strategy used achieved excellent outcomes in line with prior uniform dosing studies and thus appears to be a promising approach for maximizing local control, safety, and patient convenience."

The study "should set the stage for individualized lung SABR approaches going forward," Verma said, adding that while additional factors should be considered to further individualize treatment, "SABR dosing should (at minimum) incorporate tumor size/volume, location, and histologic type -- ideally for all patients -- rather than a 'one BED fits all' approach that unfortunately occurs too frequently even in the most modern times."

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