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Original Investigation
February 21, 2019

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non–Small Cell Lung Cancer: A Phase 2 Clinical Trial

Author Affiliations
  • 1Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada
  • 2Department of Oncology, Western University, London, Ontario, Canada
  • 3Currently with Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 4Department of Surgery, Division of Thoracic Surgery, London Health Sciences Centre, London, Ontario, Canada
  • 5Department of Pathology, Western University, London, Ontario, Canada
  • 6Department of Medical Biophysics, Western University, London, Ontario, Canada
  • 7Department of Physics and Engineering, Western University, London, Ontario, Canada
JAMA Oncol. 2019;5(5):681-688. doi:10.1001/jamaoncol.2018.6993
Key Points

Question  What are the outcomes, including the pathologic complete response rate, with neoadjuvant stereotactic ablative radiotherapy followed by surgery for early-stage non–small cell lung cancer?

Findings  In this phase 2 study of 40 patients, the pathologic complete response rate after stereotactic ablative radiotherapy was 60%. The combined treatment approach had excellent local control, a favorable toxicity profile, a 90-day postoperative mortality of 0%, and no decline in quality of life.

Meaning  The lower-than-expected pathologic complete response rate after stereotactic ablative radiotherapy suggests that patients treated with stereotactic ablative radiotherapy alone should be monitored closely for recurrence; although the treatment appears to be safe, additional interventions are required to reduce the regional and distant recurrence risks.

Abstract

Importance  Stereotactic ablative radiotherapy (SABR) is a standard treatment option in patients with medically inoperable early-stage non–small cell lung cancer (NSCLC), yet the pathologic complete response (pCR) rate after SABR is unknown. Neoadjuvant SABR in patients with cancer who are fit for resection has been hypothesized to improve local control and induce antitumor immune activity, potentially leading to better outcomes.

Objectives  To determine the pCR rate after SABR and to assess oncologic and toxicity outcomes after a combined approach of neoadjuvant SABR followed by surgery.

Design, Setting, and Participants  A phase 2, single-arm trial, with patient accrual from September 30, 2014, to August 15, 2017 (median follow-up, 19 months), was performed at a tertiary academic cancer center. Patients 18 years or older with T1T2N0M0 NSCLC and good performance status, with adequate pulmonary reserve to undergo surgical resection, were studied.

Interventions  Patients underwent neoadjuvant SABR using a risk-adapted fractionation scheme followed by surgery 10 weeks later.

Main Outcomes and Measures  The pCR rate as determined by hematoxylin-eosin staining.

Results  Forty patients (mean [SD] age, 68 [8] years; 23 [58%] female) were enrolled. Thirty-five patients underwent surgery and were evaluable for the primary end point. The pCR rate was 60% (95% CI, 44%-76%). The 30- and 90-day postoperative mortality rates were both 0%. Grade 3 or 4 toxic effects occurred in 7 patients (18%). In patients receiving surgery, 2-year overall survival was 77% (95% CI, 48%-91%), local control was 100% (95% CI, not defined), regional control was 53% (95% CI, 22%-76%), and distant control was 76% (95% CI, 45%-91%). Quality of life did not decline after treatment, with no significant changes in mean Functional Assessment of Cancer Therapy for Lung–Trial Outcome Index score during the first year of follow-up.

Conclusions and Relevance  The pCR rate after SABR for early-stage NSCLC was 60%, lower than hypothesized. The combined approach had toxic effects comparable to series of surgery alone, and there was no perioperative mortality. Further studies are needed to evaluate this combined approach compared with surgical resection alone.

Trial Registration  ClinicalTrials.gov identifier: NCT02136355

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