Initial Report of a Prospective Phase II Trial of Stereotactic Body Radiation Therapy for Patients with Medically Inoperable Stage I Non-Small Cell Lung Cancer

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 19, 2005

Presenter: R. Timmerman
Presenter's Affiliation: UT-Southwestern Medical Center
Type of Session: Scientific


Patients with medically inoperable stage I non-small cell lung cancer are potentially amenable to stereotactic body radiation therapy (SBRT), as therapeutic options in this population are limited, and local tumor control alone may lead to cure.  This phase II trial follows a phase I dose escalation protocol in the same patient population.

Materials and Methods

  • Eligible patients included those with biopsy-proven clinical T1 or T2 tumors, considered medically inoperable, and without a prior history of thoracic radiation
  • 70 patients with T1 (n=35) and T2 (n=35) tumors were prospectively enrolled between 1/02 and 9/04
  • Patients were immobilized in a stereotactic frame with abdominal compression to limit respiratory motion and received 3 fractions of 20 Gy for T1 tumors (cumulative dose 60 Gy) or 3 fractions of 22 Gy for T2 tumors (cumulative dose 66 Gy) over two weeks via a linear accelerator with 7 to 12 non-opposing, non-coplanar beams as per the prior Phase I protocol
  • Patients were followed every 3 months for evaluation of disease control and acute and late toxicity
  • Toxicity was assessed by an independent data safety monitoring committee
  • Local recurrence was defined as an enlarging mass in the vicinity of the treated site on CT imaging that was either PET-avid or biopsy-proven


  • Median follow-up for all study patients was 18 months (0.6-44 months)
  • Median age of study patients was 70 years; 69/70 had a smoking history prior to treatment, and 18/70 continued to smoke throughout treatment
  • 3/70 patients have experienced a local recurrence
  • Kaplan-Meier estimates demonstrate a median survival of 32.6 months and actuarial 1 year overall and disease-free survival of 81.1% and 79.0%, respectively)
  • No prognostic factors analyzed were found to influence overall survival
  • 8 patients have developed Grade 3-4 toxicity (pleural effusion, pneumonia/pneumonitis, declining PFTs, apnea, vocal cord palsy, skin burn) at a median of 7.5 months post-treatment, and 6 patients demonstrated Grade 5 toxicity (pneumonia, multifactorial respiratory-related, hemoptysis)
  • Tumors located in the proximal bronchial tree were more likely to be associated with increased treatment-related toxicity

Author's Conclusions

  • SBRT has a high rate of initial response and local tumor control
  • SBRT is associated with significant toxicity (Grade 3-5) in a minority of patients, and much of the observed toxicity is a late finding, demanding adequate follow-up of patients
  • Tumors in the zone of the proximal bronchial tree should not be treated with SBRT

Clinical/Scientific Implications

The phase II trial builds on a phase I dose escalation protocol for stereotactic radiation treatment of early lung tumors. Within a relatively short follow-up period, local control results are encouraging, though tempered by significant toxicity in a minority (up to 20%) of patients. As noted by the authors, the toxicity profile is not terribly surprising given the frailty of a medically inoperable patient population at baseline. Further study of this novel technique with a focus on reducing toxicity is certainly warranted.