Regional hypoxia in glioblastoma multiforme quantified with [ 18F] fluoromisonidazole positron emission tomography before radiotherapy: Correlation with time to progression and survival

Alexander M. Spence, Mark Muzi, Kristin Swanson, Finbarr O'Sullivan, Jason K. Rockhill, Joseph G. Rajendran, Tom C H Adamsen, Jeanne M. Link, Paul E. Swanson, Kevin J. Yagle, Robert C. Rostomily, Daniel L. Silbergeld, Kenneth A. Krohn

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Abstract

Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]f luoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [ 18F] fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum JIB values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≪ 0.001). In univariate analyses, greater HV or tumor T/B max were associated with shorter TTP or survival {P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/B max), magnetic resonance imaging (MRI) TIGd volume, age, and Karnovsky performance score reached significance only for HV (or T/B maxP< 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.

Original languageEnglish (US)
Pages (from-to)2623-2630
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number9
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Glioblastoma
Positron-Emission Tomography
Radiotherapy
Survival
Tumor Burden
Cell Movement
fluoromisonidazole
Hypoxia
Neoplasms
Cell Survival
Research Design
Transcription Factors
Multivariate Analysis
Magnetic Resonance Imaging
Biopsy
Drug Therapy
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Regional hypoxia in glioblastoma multiforme quantified with [ 18F] fluoromisonidazole positron emission tomography before radiotherapy : Correlation with time to progression and survival. / Spence, Alexander M.; Muzi, Mark; Swanson, Kristin; O'Sullivan, Finbarr; Rockhill, Jason K.; Rajendran, Joseph G.; Adamsen, Tom C H; Link, Jeanne M.; Swanson, Paul E.; Yagle, Kevin J.; Rostomily, Robert C.; Silbergeld, Daniel L.; Krohn, Kenneth A.

In: Clinical Cancer Research, Vol. 14, No. 9, 01.05.2008, p. 2623-2630.

Research output: Contribution to journalArticle

Spence, AM, Muzi, M, Swanson, K, O'Sullivan, F, Rockhill, JK, Rajendran, JG, Adamsen, TCH, Link, JM, Swanson, PE, Yagle, KJ, Rostomily, RC, Silbergeld, DL & Krohn, KA 2008, 'Regional hypoxia in glioblastoma multiforme quantified with [ 18F] fluoromisonidazole positron emission tomography before radiotherapy: Correlation with time to progression and survival', Clinical Cancer Research, vol. 14, no. 9, pp. 2623-2630. https://doi.org/10.1158/1078-0432.CCR-07-4995
Spence, Alexander M. ; Muzi, Mark ; Swanson, Kristin ; O'Sullivan, Finbarr ; Rockhill, Jason K. ; Rajendran, Joseph G. ; Adamsen, Tom C H ; Link, Jeanne M. ; Swanson, Paul E. ; Yagle, Kevin J. ; Rostomily, Robert C. ; Silbergeld, Daniel L. ; Krohn, Kenneth A. / Regional hypoxia in glioblastoma multiforme quantified with [ 18F] fluoromisonidazole positron emission tomography before radiotherapy : Correlation with time to progression and survival. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 9. pp. 2623-2630.
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abstract = "Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]f luoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [ 18F] fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum JIB values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≪ 0.001). In univariate analyses, greater HV or tumor T/B max were associated with shorter TTP or survival {P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/B max), magnetic resonance imaging (MRI) TIGd volume, age, and Karnovsky performance score reached significance only for HV (or T/B maxP< 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.",
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T1 - Regional hypoxia in glioblastoma multiforme quantified with [ 18F] fluoromisonidazole positron emission tomography before radiotherapy

T2 - Correlation with time to progression and survival

AU - Spence, Alexander M.

AU - Muzi, Mark

AU - Swanson, Kristin

AU - O'Sullivan, Finbarr

AU - Rockhill, Jason K.

AU - Rajendran, Joseph G.

AU - Adamsen, Tom C H

AU - Link, Jeanne M.

AU - Swanson, Paul E.

AU - Yagle, Kevin J.

AU - Rostomily, Robert C.

AU - Silbergeld, Daniel L.

AU - Krohn, Kenneth A.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]f luoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [ 18F] fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum JIB values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≪ 0.001). In univariate analyses, greater HV or tumor T/B max were associated with shorter TTP or survival {P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/B max), magnetic resonance imaging (MRI) TIGd volume, age, and Karnovsky performance score reached significance only for HV (or T/B maxP< 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.

AB - Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]f luoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [ 18F] fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum JIB values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≪ 0.001). In univariate analyses, greater HV or tumor T/B max were associated with shorter TTP or survival {P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/B max), magnetic resonance imaging (MRI) TIGd volume, age, and Karnovsky performance score reached significance only for HV (or T/B maxP< 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.

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