Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography

Wui Jin Koh, Kenneth S. Bergman, Janet S. Rasey, Lanell M. Peterson, Margaret L. Evans, Michael M. Graham, John R. Grierson, Karen L. Lindsley, Thomas K. Lewellen, Kenneth Krohn, Thomas W. Griffin

Research output: Contribution to journalArticle

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Abstract

Purpose: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studies in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. Methods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio ≥ 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 20-84% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

Original languageEnglish (US)
Pages (from-to)391-398
Number of pages8
JournalInternational journal of radiation oncology, biology, physics
Volume33
Issue number2
DOIs
StatePublished - Sep 30 1995
Externally publishedYes

Fingerprint

oxygenation
Non-Small Cell Lung Carcinoma
Positron-Emission Tomography
lungs
radiation therapy
positrons
Radiotherapy
tumors
tomography
cancer
evaluation
hypoxia
Neoplasms
pretreatment
Tumor Burden
fluoromisonidazole
Residual Neoplasm
Patient Selection
Clinical Trials
Radiation

Keywords

  • Positron emission tomography
  • Radiotherapy
  • Tumor hypoxia
  • Tumor oxygenation
  • [F-18]fluoromisonidazole

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. / Koh, Wui Jin; Bergman, Kenneth S.; Rasey, Janet S.; Peterson, Lanell M.; Evans, Margaret L.; Graham, Michael M.; Grierson, John R.; Lindsley, Karen L.; Lewellen, Thomas K.; Krohn, Kenneth; Griffin, Thomas W.

In: International journal of radiation oncology, biology, physics, Vol. 33, No. 2, 30.09.1995, p. 391-398.

Research output: Contribution to journalArticle

Koh, Wui Jin ; Bergman, Kenneth S. ; Rasey, Janet S. ; Peterson, Lanell M. ; Evans, Margaret L. ; Graham, Michael M. ; Grierson, John R. ; Lindsley, Karen L. ; Lewellen, Thomas K. ; Krohn, Kenneth ; Griffin, Thomas W. / Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. In: International journal of radiation oncology, biology, physics. 1995 ; Vol. 33, No. 2. pp. 391-398.
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abstract = "Purpose: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studies in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. Methods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio ≥ 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84{\%} (median 58{\%}). Subsequent FHVs varied from 8-79{\%} (median 29{\%}) at midtreatment, and ranged from 20-84{\%} (median 22{\%}) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.",
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T1 - Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography

AU - Koh, Wui Jin

AU - Bergman, Kenneth S.

AU - Rasey, Janet S.

AU - Peterson, Lanell M.

AU - Evans, Margaret L.

AU - Graham, Michael M.

AU - Grierson, John R.

AU - Lindsley, Karen L.

AU - Lewellen, Thomas K.

AU - Krohn, Kenneth

AU - Griffin, Thomas W.

PY - 1995/9/30

Y1 - 1995/9/30

N2 - Purpose: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studies in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. Methods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio ≥ 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 20-84% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

AB - Purpose: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studies in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. Methods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio ≥ 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 20-84% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

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KW - Radiotherapy

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KW - Tumor oxygenation

KW - [F-18]fluoromisonidazole

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