Impact of brachytherapy on local recurrence after sublobar resection: Results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small cell lung cancer (NSCLC)

Reporter: Saumil Gandhi, MD PhD
The Abramson Cancer Center at the University of Pennsylvania
Last Modified: June 7, 2013

Presenter: Hiran Chrishantha Fernando, MBBS
Presenter's Affiliation: Boston Medical Center, Boston University


  • Standard surgical treatment for Stage I lung cancer consists of lobectomy and mediastinal node dissection with local recurrence rates as low as 5-6%.
  • However, many patients are unable to tolerate a lobectomy due to poor pulmonary function.
  • A sublobar resection of peripheral tumors is often associated with inadequate tumor margins and local recurrence rates as high as 20%.
  • Adjuvant brachytherapy has the potential to reduce local recurrence after sublobar resection for NSCLC.
  • This is a multicenter randomized study of SR versus SR + brachytherapy (SRB). The goal is to determine whether Stage I NSCLC patients treated with SRB have a longer time to local recurrence compared to patients treated with SR alone.


  • Stage I NSCLC patients (tumors < 3cm) with high operable risk were randomized to SR or SRB.
  • Criteria for high operable risk were pre-defined based on various objective parameters including FEV1, DLCO, age, left ventricular function, resting and exercise arterial oxygen partial pressure.
  • In the SRB arm, I125 seeds were incorporated into Vicryl sutures or Vicryl mesh and placed over the staple line after SR.
  • The primary endpoint was time to local recurrence, which was defined as recurrence within the primary tumor lobe at the staple line, away from the staple line, or within the hilar nodes.
  • Imaging evidence of local recurrence was confirmed with either a needle biopsy or PET scan.
  • The trial was designed to have 90% power to detect a hazard ratio (HR) of 0.315 in favor of the SRB arm using a one-sided ? of 0.05 with a sample size of 100 patients per arm.
  • Serial CT scans were obtained for 36 months during follow-up.


  • A total of 224 patients were randomized, of which 213 were eligible.
  • 109 patients were randomized to the SR arm and 104 patients were randomized to the SRB arm.
  • No differences were found in baseline characteristics between the two groups.
  • There was no difference in Grade 3 or higher adverse events between the two arms.
  • Median (range) follow-up was 4.06 (0.04, 5.0) years.
  • There was no significant difference between the arms in time to local recurrence (HR = 0.87; 5% CI: 0.41, 1.86, p=0.72).
  • There was no difference in the rate of local recurrence between SR and SRB arms (12.8% versus 12.5%, p=0.94).
  • There was no difference in the location of local recurrence between SR and SRB arms: At the staple line (6.4% versus 4.8%, p=0.94); away from the staple line (3.7% versus 3.8%, p=1.00); nodal (1.8% versus 3.8%, p=0.44).
  • SRB did not reduce the rate of local recurrence in patients with a compromised surgical margin (margin < 1cm; margin:tumor ratio <1; positive staple line cytology).
  • There was no significant difference in overall survival between SR (71%) and SRB (72%) (p=0.81) at 3 years.

Author's Conclusions

  • Adjuvant intraoperative brachytherapy does not improve local recurrence or survival
  • Sublobar resection only should continue to be the standard of care for high-risk patients.

Clinical Implications

  • In this multiinstitutional phase III randomized study, the authors show that there is no role for intraoperative brachytherapy in the treatment of patients with Stage I lung cancer.
  • The authors conclude that local recurrence rate after sublobar resection is low and it should be the standard of care for high-risk patients. However, the local recurrence rates observed here are significantly lower than 20% recurrence rates reported previously.
  • Although sublobar resection is currently the standard of care for high-risk patients, stereotactic body radiation therapy may play an increasingly important role in the treatment of these patients in the future. Further studies comparing sublobar resection to stereotactic body radiation therapy are needed in this subset of patients.