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Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials
Joe Y Chang 1, Suresh Senan 2, Marinus A Paul 3, Reza J Mehran 4, Alexander V Louie 2, Peter Balter 5, Harry J M Groen 6, Stephen E McRae 7, Joachim Widder 8, Lei Feng 9, Ben E E M van den Borne 10, Mark F Munsell 9, Coen Hurkmans 11, Donald A Berry 9, Erik van Werkhoven 12, John J Kresl 13, Anne-Marie Dingemans 14, Omar Dawood 15, Cornelis J A Haasbeek 2, Larry S Carpenter 16, Katrien De Jaeger 11, Ritsuko Komaki 17, Ben J Slotman 2, Egbert F Smit 18, Jack A Roth 4
Surgical resection with lobectomy is consid- ered a standard of care for medically operable patients with stage I non-small cell lung cancer. Over the past decade, precision radiation therapy called stereotactic body radiotherapy (SABR), typically delivering biologically effective doses of greater than 100 Gy in just a few large frac- tions of pinpoint radiation to the tumor with small margin, has been utilized to effectively treat stage I non-small cell lung cancer. Multiple random- ized trials comparing lobectomy to SABR in medically operable stage I non-small cell lung cancer patients failed to accrue an adequate num- ber of patients.
This study by Chang et al. pooled data from the STARS and ROSEL phase 3 randomized tri- als comparing lobectomy with SABR in patients with T1-T2AN0 stage I AJCC 7th edition non- small cell lung cancer. The primary endpoint was overall survival, and secondary endpoints were recurrence-free survival and grade 3 or higher chronic toxicity. Fifty-eight patients were ran- domized in the combined trials, and median fol- low-up was 40.2 months for patients randomized to SABR and 35.4 months for patients random- ized to surgery (Fig. 3.1).
Key Point The numbers in this pooled analysis are small. However, the overall survival was sig- nificantly improved in the SABR arm compared with the surgery arm (log-rank P = 0.037; HR 0.14, 95% CI 0.017–1.190). A total of seven patients died during follow-up, six in the surgery arm and one in the SABR arm (Table 3.1 and Fig. 3.2).
Fig. 3.1 Study schema for pooled analysis of STARS and ROSEL trials. (From Chang et al. Lancet Oncol. 16: 630–7, 2015 with permission)
Table 3.1 Pooled estimate of overall survival with SABR and lobectomy at 1 and 3 years
Pooled estimate overall survival | 1-year overall survival (%) | 3-year overall survival (%) | | | | | | |
Fig. 3.2 Overall survival and recurrence-free survival on pooled analysis of the STARS and ROSEL trials. (From Chang et al. Lancet Oncol. 16:630–7, 2015 with permission)
There was no significant difference in local, regional, or distant metastasis between the two arms of the trial. This was largely due to the small number of patients accrued to the trials. A single local recurrence in the SABR arm of the trial was salvaged with surgery.
Key Point The rate of grade 3 or higher treatment-related adverse events was higher in the lobectomy arm of the trial compared with the SABR arm of the trial. The rate of grade 3–4 adverse events was 44% with surgery. The rate of grade 3 adverse events was 10% with SABR, and there were no grade 4 adverse events with SABR.
This landmark report was the first analysis of pooled data from prospective phase 3 random- ized trials comparing lobectomy with SABR. The results demonstrated that SABR may lead to improved survival compared with surgery and that SABR is better tolerated that surgery. The accrual numbers on these two trials were small, and the investigators call for additional random- ized trials in early-stage non-small cell lung can- cer comparing SABR to lobectomy. Chang et al. stated, “Physicians should interpret these find- ings as confirmation of at least clinical equipoise between SABR and surgical options and should consider SABR as an option for treatment of operable stage 1 NSCLC.”
Chang JY, Senan S, Paul MA, Mehran RJ, Louie AV, Balter P, Groen HJ, McRae SE, Widder J, Feng L, van den Borne BE, Munsell MF, Hurkmans C, Berry DA, van Werkhoven E, Kresl JJ, Dingemans AM, Dawood O, Haasbeek CJ, Carpenter LS, De Jaeger K, Komaki R, Slotman BJ, Smit EF, Roth JA. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015 Jun;16(6):630-7. doi: 10.1016/S1470-2045(15)70168-3. Epub 2015 May 13. Erratum in: Lancet Oncol. 2015 Sep;16(9):e427. PMID: 25981812; PMCID: PMC4489408.
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