Stereotactic ablative radiotherapy tops for inoperable early non-small-cell lung cancer

By Reuters Staff

NEW YORK (Reuters Health) - 21/2/2019

Compared with standard radiotherapy, stereotactic ablative body radiotherapy (SABR) provides better local control and improved survival in patients with inoperable peripherally located stage 1 non-small-cell lung cancer (NSCLC), according to results of the CHISEL study.

"The findings of this trial suggest that SABR should be the treatment of choice for this patient group," the study team concludes in The Lancet Oncology, online February 12.

While SABR is widely used to treat inoperable early-stage NSCLC, CHISEL is the first randomized controlled trial comparing it to standard radiotherapy, Dr. David Ball from the Peter MacCallum Cancer Center, in Melbourne, and colleagues note.

The trial enrolled 101 patients with peripherally located stage-1 NSCLC who were either unfit for surgery or refused surgery; 35 were randomly allocated to conventional radiotherapy (66 Gy in 33 fractions of 2 Gy or 50 Gy in 20 fractions of 2.5 Gy) and 66 to SABR (54 Gy in three 18-Gy fractions or 48 Gy in four 12-Gy fractions).

Five patients (7.6%) in the SABR arm and two (6.5%) in the standard radiotherapy arm did not receive treatment, and a further four in each group withdrew before the end of the study. As of July 31, 2017 (data cutoff), median follow-up for local treatment failure was 2.1 years in the standard arm and 2.6 years in the SABR arm.

Compared with standard radiotherapy, SABR provided improvements in freedom from local failure, the primary endpoint (hazard ratio, 0.32; P=0.008). It also boosted overall survival, the secondary endpoint, with two-year overall survival of 77% in the SABR arm and 59% in the standard radiotherapy arm.

SABR was well tolerated and was not associated with a decline in quality of life. In the SABR arm, there was one grade 4 adverse event (dyspnea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnea and one fatigue) deemed related to treatment, compared with two grade 3 events (chest pain) in the standard arm.

The investigators note that since CHISEL was completed, two large retrospective non-randomized studies and one systematic review have reported a survival benefit associated with SABR compared with standard radiotherapy, consistent with their results.

CHISEL is a "major step forward" and "establishes SABR as the standard radiotherapy approach in patients with stage 1 NSCLC who are not undergoing surgery," write the authors of a comment published with the study.

Dr. Faiez AlShafa and Dr. David Palma from the division of radiation oncology at London Health Sciences Centre, in Canada, say a limitation of the study is the primary endpoint of local failure, which can be hard to ascertain on imaging in the setting of post-SABR fibrotic changes.

"This limitation is mitigated by the strong overall survival benefit detected in the trial - an endpoint unaffected by the limitations of imaging," they write.

A "tantalizing unknown," they add, is the impact of combining SABR with immunotherapy. "Tumor cell death induced by SABR can trigger innate immunity, increase recruitment of immune cells, and activate the body's adaptive immunity. Perhaps the immune-stimulatory effects of SABR in conjunction with immunotherapy will bring advances in the treatment of early-stage NSCLC; this combined treatment will be tested in upcoming randomized controlled trials," they note.

CHISEL also shows that "excellent" two-year overall survival can be achieved in patients unfit for surgery, write Drs. AlShafa and Palma. "Concluding that overall survival would be higher in a fitter population of medically operable patients, in which the risk of death from comorbidity would be lower, is reasonable. This idea leads to the question of whether SABR should be an alternative to surgical resection in patients who are operable."

SOURCE: http://bit.ly/2V3o5GY and http://bit.ly/2tsTneK

Lancet Oncol 2019.

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