Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235

  • Jose G. BazanEmail author
  • Fenghai Duan
  • Bradley S. Snyder
  • Dunstan Horng
  • Edward E. Graves
  • Barry A. Siegel
  • Mitchell Machtay
  • Billy W. LooJrEmail author
Original Article



To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT).


This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan–Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS.


Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61–69 Gy or ≥70 Gy (p = 0.001).


Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.


Metabolic tumor volume FDG-PET NSCLC SUV 



Dr. Duan and Mr. Snyder had access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Bazan, Loo

Acquisition, analysis or interpretation of data: Bazan, Loo, Duan, Snyder

Drafting of the manuscript: Bazan, Loo, Duan, Snyder

Critical revision of the manuscript for important intellectual content: All authors

Statistical analysis: Duan, Snyder

Compliance with ethical standards


ACRIN receives funding from the National Cancer Institute through grants U01 CA079778 and UO1 CA080098.

Conflict of interest

Dr. Loo receives research support from Varian Medical Systems and RaySearch Laboratories, and is a board member of TibaRay, Inc. Authors Jose G. Bazan, Fenghai Duan, Bradley S. Snyder, Dunstan Horng, Edward E. Graves, Barry A. Siegel, and Mitchell Machtay declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2016_3520_MOESM1_ESM.docx (124 kb)
ESM 1 (DOCX 124 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jose G. Bazan
    • 1
    Email author
  • Fenghai Duan
    • 2
  • Bradley S. Snyder
    • 3
  • Dunstan Horng
    • 4
  • Edward E. Graves
    • 5
  • Barry A. Siegel
    • 6
  • Mitchell Machtay
    • 7
  • Billy W. LooJr
    • 5
    Email author
  1. 1.Department of Radiation OncologyThe Ohio State UniversityColumbusUSA
  2. 2.Department of Biostatistics and Center for Statistical SciencesBrown University School of Public HealthProvidenceUSA
  3. 3.Center for Statistical SciencesBrown University School of Public HealthProvidenceUSA
  4. 4.ECOG-ACRIN Cancer Research GroupPhiladelphiaUSA
  5. 5.Department of Radiation Oncology, Stanford Cancer Institute, School of MedicineStanford UniversityStanfordUSA
  6. 6.Mallinckrodt Institute of Radiology and the Siteman Cancer CenterWashington University School of MedicineSt. LouisUSA
  7. 7.Case Comprehensive Cancer Center and Case Western Reserve UniversityUniversity Hospitals Seidman Cancer CenterClevelandUSA

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