Pretreatment FDG-PET metrics in stage III non-small cell lung cancer: ACRIN 6668/RTOG 0235

Nitin Ohri, Fenghai Duan, Mitchell MacHtay, Jeremy J. Gorelick, Bradley S. Snyder, Abass Alavi, Barry A. Siegel, Douglas W. Johnson, Jeffrey D. Bradley, Albert Denittis, Maria Werner-Wasik

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with <sup>18</sup>F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUV<inf>max</inf>), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm<sup>3</sup> increase, 95% CI = 1.03 to 1.06, P <. 001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm<sup>3</sup> increase, 95% CI = 1.08 to 1.23, P <. 001) and at six months (HR = 1.05 per 10cm<sup>3</sup> increase, 95% CI = 1.02 to 1.07, P <. 001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume107
Issue number4
DOIs
StatePublished - Apr 1 2015

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Non-Small Cell Lung Carcinoma
Tumor Burden
Fluorodeoxyglucose F18
Chemoradiotherapy
Survival
Survival Analysis
Platinum
Proportional Hazards Models
Positron-Emission Tomography
Clinical Trials
Therapeutics
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Pretreatment FDG-PET metrics in stage III non-small cell lung cancer : ACRIN 6668/RTOG 0235. / Ohri, Nitin; Duan, Fenghai; MacHtay, Mitchell; Gorelick, Jeremy J.; Snyder, Bradley S.; Alavi, Abass; Siegel, Barry A.; Johnson, Douglas W.; Bradley, Jeffrey D.; Denittis, Albert; Werner-Wasik, Maria.

In: Journal of the National Cancer Institute, Vol. 107, No. 4, 01.04.2015.

Research output: Contribution to journalArticle

Ohri, N, Duan, F, MacHtay, M, Gorelick, JJ, Snyder, BS, Alavi, A, Siegel, BA, Johnson, DW, Bradley, JD, Denittis, A & Werner-Wasik, M 2015, 'Pretreatment FDG-PET metrics in stage III non-small cell lung cancer: ACRIN 6668/RTOG 0235', Journal of the National Cancer Institute, vol. 107, no. 4. https://doi.org/10.1093/jnci/djv004
Ohri, Nitin ; Duan, Fenghai ; MacHtay, Mitchell ; Gorelick, Jeremy J. ; Snyder, Bradley S. ; Alavi, Abass ; Siegel, Barry A. ; Johnson, Douglas W. ; Bradley, Jeffrey D. ; Denittis, Albert ; Werner-Wasik, Maria. / Pretreatment FDG-PET metrics in stage III non-small cell lung cancer : ACRIN 6668/RTOG 0235. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 4.
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title = "Pretreatment FDG-PET metrics in stage III non-small cell lung cancer: ACRIN 6668/RTOG 0235",
abstract = "Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm3 increase, 95{\%} CI = 1.03 to 1.06, P <. 001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm3 increase, 95{\%} CI = 1.08 to 1.23, P <. 001) and at six months (HR = 1.05 per 10cm3 increase, 95{\%} CI = 1.02 to 1.07, P <. 001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.",
author = "Nitin Ohri and Fenghai Duan and Mitchell MacHtay and Gorelick, {Jeremy J.} and Snyder, {Bradley S.} and Abass Alavi and Siegel, {Barry A.} and Johnson, {Douglas W.} and Bradley, {Jeffrey D.} and Albert Denittis and Maria Werner-Wasik",
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T1 - Pretreatment FDG-PET metrics in stage III non-small cell lung cancer

T2 - ACRIN 6668/RTOG 0235

AU - Ohri, Nitin

AU - Duan, Fenghai

AU - MacHtay, Mitchell

AU - Gorelick, Jeremy J.

AU - Snyder, Bradley S.

AU - Alavi, Abass

AU - Siegel, Barry A.

AU - Johnson, Douglas W.

AU - Bradley, Jeffrey D.

AU - Denittis, Albert

AU - Werner-Wasik, Maria

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Y1 - 2015/4/1

N2 - Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm3 increase, 95% CI = 1.03 to 1.06, P <. 001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm3 increase, 95% CI = 1.08 to 1.23, P <. 001) and at six months (HR = 1.05 per 10cm3 increase, 95% CI = 1.02 to 1.07, P <. 001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.

AB - Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm3 increase, 95% CI = 1.03 to 1.06, P <. 001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm3 increase, 95% CI = 1.08 to 1.23, P <. 001) and at six months (HR = 1.05 per 10cm3 increase, 95% CI = 1.02 to 1.07, P <. 001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.

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