Positron Emission Tomography in Staging Early Lung Cancer

A Randomized Trial

  1. Donna E. Maziak, MDCM;
  2. Gail E. Darling, MD;
  3. Richard I. Inculet, MD;
  4. Karen Y. Gulenchyn, MD;
  5. Albert A. Driedger, MD;
  6. Yee C. Ung, MD;
  7. John D. Miller, MD;
  8. Chu-Shu Gu, MSc;
  9. Kathryn J. Cline, BSc;
  10. William K. Evans, MD; and
  11. Mark N. Levine, MD, MSc
  1. From the Ontario Clinical Oncology Group, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.

    Abstract

    Background: Among patients with early-stage non–small cell lung cancer (NSCLC), preoperative imaging tests are important in defining surgical candidates.

    Objective: To assess whether whole-body positron emission tomography and computed tomography (PET-CT) plus cranial imaging correctly upstages cancer in more patients with NSCLC than does conventional staging plus cranial imaging.

    Design: Randomized clinical trial with recruitment from June 2004 to August 2007. The centralized, computer-generated, variable block size randomization scheme was stratified by treatment center and cancer stage. Participants, health care providers, and outcome assessors were not blinded to imaging modality assignment.

    Setting: 8 hospitals and 5 PET-CT centers in academic institutions.

    Patients: Eligible patients were older than 18 years; had histologic or cytologic proof of stage I, II, or IIIA NSCLC on the basis of chest radiography and thoracic CT; and had a tumor considered to be resectable.

    Intervention: PET-CT or conventional staging (abdominal CT and bone scan). All patients also had cranial imaging using CT or magnetic resonance imaging.

    Measurements: The primary outcome was correct upstaging, thereby avoiding stage-inappropriate surgery. Secondary outcomes were incorrect upstaging and incorrect understaging.

    Results: 170 patients were assigned to PET-CT and 167 to conventional staging. Eight patients (3 who had PET-CT and 5 who had conventional staging) did not have planned surgery. Disease was correctly upstaged in 23 of 167 PET-CT recipients and 11 of 162 conventional staging recipients (13.8% vs. 6.8%; difference, 7.0 percentage points [95% CI, 0.3 to 13.7 percentage points]), thereby sparing these patients from surgery. Disease was incorrectly upstaged in 8 PET-CT recipients and 1 conventional staging recipient (4.8% vs. 0.6%; difference, 4.2 percentage points [CI, 0.5 to 8.6 percentage points]), and it was incorrectly understaged in 25 and 48 patients, respectively (14.9% vs. 29.6%; difference, 14.7 percentage points [CI, 5.7 to 23.4 percentage points]). At 3 years, 52 patients who had PET-CT and 57 patients who had conventional staging had died.

    Limitation: The relatively small sample and the fact that some patients did not have planned surgery limited the ability to determine precise differences in clinical outcomes that were attributable to testing strategies.

    Conclusion: Preoperative staging with PET-CT and cranial imaging identifies more patients with mediastinal and extrathoracic disease than conventional staging, thereby sparing more patients from stage-inappropriate surgery, but the strategy also incorrectly upstaged disease in more patients.

    Primary Funding Source: Ontario Ministry of Health and Long-Term Care, Canadian Institutes of Health Research, and Cancer Care Ontario.

    Article and Author Information

    • Acknowledgment: The authors thank Jim Julian for his help with the manuscript, the members of the data safety monitoring committee (Jonathan Sussman [Chair], Ralph Meyer, and Lehana Thabane), the members of the central adjudication committee (Ian Dayes, Bindi Dhesy, and Jim Wright), and data management assistant Sharon Nason.

    • Grant Support: By the Ontario Ministry of Health and Long-Term Care (grant 06126) and the Canadian Institutes of Health Research (grant MCT-78777), and support from Cancer Care Ontario.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Reproducible Research Statement: Study protocol: Available at www.ocog.ca. Data set and statistical code: Not available.

    • Requests for Single Reprints: Mark N. Levine, MD, MSc, Ontario Clinical Oncology Group, Hamilton Health Sciences, Henderson Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada; e-mail, mlevine{at}mcmaster.ca.

    • Current Author Addresses: Dr. Maziak: University of Ottawa, Division of Thoracic Surgery, The Ottawa Hospital, 501 Smyth Road, 6NW-6364, Ottawa, Ontario K1H 8L6, Canada.

    • Dr. Darling: University of Toronto, Division of Thoracic Surgery, Toronto General Hospital, 200 Elizabeth Street, Room 9N-955, Toronto, Ontario M5G 2C4, Canada.

    • Dr. Inculet: University of Western Ontario, Division of Thoracic Surgery, Victoria Hospital, 800 Commissioners Road East, Suite E2-122, London, Ontario N6A 5W9, Canada.

    • Dr. Gulenchyn: McMaster University, Department of Nuclear Medicine, Hamilton Health Sciences, 1200 Main Street West, Room 1P15, Hamilton, Ontario L8N 3Z5, Canada.

    • Dr. Driedger: University of Western Ontario, Department of Nuclear Medicine, London Health Sciences Centre, 375 South Street, Victoria Campus, London, Ontario N6A 4G5, Canada.

    • Dr. Ung: University of Toronto, Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

    • Dr. Miller: McMaster University, Division of Thoracic Surgery, St. Joseph's Healthcare, Room G819, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

    • Mr. Gu, Ms. Cline, and Dr. Levine: McMaster University, Department of Oncology, Ontario Clinical Oncology Group, Hamilton Health Sciences, Henderson Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

    • Dr. Evans: McMaster University, Department of Oncology, Juravinski Cancer Centre, Hamilton Health Sciences, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada.

    • Author Contributions: Conception and design: D.E. Maziak, G.E. Darling, K.Y. Gulenchyn, Y.C. Ung, W.K. Evans, M.N. Levine.

    • Analysis and interpretation of the data: D.E. Maziak, G.E. Darling, K.Y. Gulenchyn, Y.C. Ung, J.D. Miller, C.S. Gu, K.J. Cline, W.K. Evans, M.N. Levine.

    • Drafting of the article: D.E. Maziak, G.E. Darling, K.Y. Gulenchyn, Y.C. Ung, C.S. Gu, K.J. Cline, W.K. Evans, M.N. Levine.

    • Critical revision of the article for important intellectual content: D.E. Maziak, G.E. Darling, K.Y. Gulenchyn, J.D. Miller, C.S. Gu, K.J. Cline, W.K. Evans, M.N. Levine.

    • Final approval of the article: D.E. Maziak, G.E. Darling, R.I. Inculet, K.Y. Gulenchyn, A.A. Driedger, Y.C. Ung, J.D. Miller, W.K. Evans, M.N. Levine.

    • Provision of study materials or patients: D.E. Maziak, G.E. Darling, R.I. Inculet, K.Y. Gulenchyn, Y.C. Ung, J.D. Miller.

    • Statistical expertise: C.S. Gu.

    • Obtaining of funding: D.E. Maziak, W.K. Evans, M.N. Levine.

    • Administrative, technical, or logistic support: A.A. Driedger, K.J. Cline, M.N. Levine.

    • Collection and assembly of data: D.E. Maziak, K.Y. Gulenchyn, A.A. Driedger, C.S. Gu, K.J. Cline.

    • Clinicaltrials.gov registration number: NCT00136890.

    Responses to this article

    • Use standard diagnostic language
      • Martin Hellmich
      Ann Intern Med published online October 26, 2009
    • If the objective of the study had been little different
      • Udip Dahal and
      • Bandana Pathak
      Ann Intern Med published online October 26, 2009
    « Previous | Next Article »Table of Contents

    This Article

    1. Ann Intern Med August 18, 2009 vol. 151 no. 4 221-228
    1. » Abstract
    2. Figures
    3. Full Text
    4. Full Text (PDF)
    5. CME Course

    Current Issue

    1. November 3, 2009, 151 (9)
    1. Alert me to current issues