This is a phase II multi-institutional randomized trial evaluating single fraction SBRT 30 Gy versus three fraction 60 Gy for peripheral NSCLC in medically inoperable patients. The primary endpoint of this study was grade three or higher thoracic toxicity and other adverse events. Secondary endpoints included local control, progression free survival, overall survival, and quality of life. 

From 2008 to 2015, 98 patients were randomized and reported with 53.8 months median follow up. There were ten patients lost to follow up, 9 of which were on the three fraction arm.  

For the primary endpoint, 16% on the single fraction arm and 12% on the three fraction arm experienced a grade three thoracic adverse event, no grade 4-5 were reported. There were no statistically significant differences in local control, progression free survival, and overall survival endpoints. The OS at 2 years was 73% versus 62% and PFS at 2 years was 65% versus 50% for single and three fraction arms, respectively.  On quality of life questionnaires patients in the single fraction arm reported significantly better dyspnea at six months and better social functioning at three and six months. There was no change in pulmonary function tests compared with baseline in both arms. 

In conclusion, this is a phase II randomized study compared single versus three fraction SBRT for peripheral NSCLC in medically inoperable patients. The primary endpoint, grade 3 thoracic adverse events, was not significantly different between arms, nor were any of the secondary endpoints of local control, progression free survival, and overall survival. Patients who received single fraction SBRT reported improved dyspnea and social functioning in follow up questionnaires.  This study concludes that single fraction is safe and effective, although one should note that efficacy was limited to secondary endpoints.

Reference (PubMed Link): Singh AK, Gomez-Suescun JA, Stephans KL, et al. One versus three fractions of stereotactic body radiation therapy for peripheral stage i to ii non-small cell lung cancer: A randomized, multi-institution, phase 2 trial. Int J Radiat Oncol Biol Phys 2019;105:752-759.

Key Institution: Multi-institutional/USA 
Keywords: Single fraction, SBRT, NSCLC 

This trial evaluated the use of SBRT for early stage lung cancer patients who were operable, whereas historically SBRT was reserved for medically inoperable patients. The primary endpoint was local control, and survival, adverse events, and the incidence of surgical salvage, as secondary endpoints.

With median follow up of 48.1 months, 26 of 33 enrolled patients were evaluable. Of those evaluable 23/26 were T1 and 3 were T2. The median FEV1 and DLCO were 72% (38-136) and 68% (22-96), respectively.

One patient had primary tumor recurrence; 4 year local control 96%. OS and DFS at 4 years was 56% and 57%, respectively. LRC at 4 years was 88% (3 regional failures) and DM rate was 12% (5 patients). Grade 3 AE rate 14%, no grade 4.

SBRT appears to have a high probability of tumor control, low morbidity, and little need for surgical salvage in patients with early-stage operable lung cancer.

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This paper is a NCDB analysis of early-stage NSCLC that shows improved 30-day mortality with SABR vs. surgery. The authors identified 76,623 patients who were treated with surgery or SABR for early-stage NSCLC (T1-T2a N0 M0) and compared their 30-day and 90-day post-treatment

Patients with SABR had significantly improved mortality at both 30-days and 90-days compared to patients who received surgery in both unmatched and propensity-matched analyses. Elder patients (>70 years) had greatest mortality benefit with SABR vs. surgery. Patients treated with pneumonectomy had worst absolute mortality as would be expected. These results strongly show that SABR may be safer than surgery especially in the peri-treatment period and for elderly patients, as we would intuitively expect. This is despite SABR patients typically being chosen because they are poor operative candidates, thus generally being frailer. This study has limitations as a retrospective NCDB analysis, with the cohorts not being perfectly matched, as shown in table 1 with nearly every pre-treatment treatment/site/stage/epidemiologic factor being significantly different between the surgery and SABR groups. Also, the authors limit the analysis to only T1-T2a patients and don’t include T2b N0 patients who are also generally strong candidates for both lobectomy and for SABR. In addition, there is no data on survival/mortality beyond the 90 day period; it would be interesting to see if any of the early mortality trends continued subsequently and if that also correlated with age. Still, despite these limitations, this paper is probably the largest and strongest to date showing that for older patients SABR may be strongly preferable to surgery to decrease risk of peri-treatment mortality. It is thus potentially practice-changing especially for older patients who are borderline surgical candidates, as physicians may be more likely to recommend SABR based on the results of this study.

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