Prognostic significance of hypoxic PET using 18F-FAZA and 62Cu-ATSM in non-small-cell lung cancer

Tomonari Kinoshita, Hirofumi Fujii, Yuichiro Hayashi, Ikuo Kamiyama, Takashi Ohtsuka, Hisao Asamura

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). Patients and methods: Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: 18F-fluoroazomycin arabinoside (18F-FAZA) (n=45) and/or 62Cu-diacetyl-bis (N4)-methylsemithiocarbazone (62Cu-ATSM) (n=22). All received 18F-fluorodeoxyglucose (18F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. Results: A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of 18F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs (18F-FAZA, p62Cu-ATSM, p18F-FDG. The patients with a higher accumulation had significantly poorer overall survival [18F-FAZA, HR (hazard ratio), 9.50, p62Cu-ATSM, HR, 4.06, p18F-FAZA, HR, 5.28, p62Cu-ATSM, HR, 2.72, p18F-FAZA and 62Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.

Original languageEnglish
Pages (from-to)56-66
Number of pages11
JournalLung Cancer
Volume91
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Diacetyl
Non-Small Cell Lung Carcinoma
Positron-Emission Tomography
Fluorodeoxyglucose F18
Neoplasms
Survival
Molecular Imaging
Chemoradiotherapy
Blood Vessels
Neutrophils
fluoroazomycin arabinoside
Lymphocytes
Therapeutics

Keywords

  • F-fluoroazomycin arabinoside
  • F-fluorodeoxyglucose
  • Cu-diacetyl-bis (N4)-methylsemithiocarbazone
  • Hypoxic positron emission tomography
  • Non-small-cell lung cancer
  • Prognostic factor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Prognostic significance of hypoxic PET using 18F-FAZA and 62Cu-ATSM in non-small-cell lung cancer. / Kinoshita, Tomonari; Fujii, Hirofumi; Hayashi, Yuichiro; Kamiyama, Ikuo; Ohtsuka, Takashi; Asamura, Hisao.

In: Lung Cancer, Vol. 91, 01.01.2016, p. 56-66.

Research output: Contribution to journalArticle

Kinoshita, Tomonari ; Fujii, Hirofumi ; Hayashi, Yuichiro ; Kamiyama, Ikuo ; Ohtsuka, Takashi ; Asamura, Hisao. / Prognostic significance of hypoxic PET using 18F-FAZA and 62Cu-ATSM in non-small-cell lung cancer. In: Lung Cancer. 2016 ; Vol. 91. pp. 56-66.
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T1 - Prognostic significance of hypoxic PET using 18F-FAZA and 62Cu-ATSM in non-small-cell lung cancer

AU - Kinoshita, Tomonari

AU - Fujii, Hirofumi

AU - Hayashi, Yuichiro

AU - Kamiyama, Ikuo

AU - Ohtsuka, Takashi

AU - Asamura, Hisao

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objectives: Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). Patients and methods: Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: 18F-fluoroazomycin arabinoside (18F-FAZA) (n=45) and/or 62Cu-diacetyl-bis (N4)-methylsemithiocarbazone (62Cu-ATSM) (n=22). All received 18F-fluorodeoxyglucose (18F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. Results: A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of 18F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs (18F-FAZA, p62Cu-ATSM, p18F-FDG. The patients with a higher accumulation had significantly poorer overall survival [18F-FAZA, HR (hazard ratio), 9.50, p62Cu-ATSM, HR, 4.06, p18F-FAZA, HR, 5.28, p62Cu-ATSM, HR, 2.72, p18F-FAZA and 62Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.

AB - Objectives: Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). Patients and methods: Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: 18F-fluoroazomycin arabinoside (18F-FAZA) (n=45) and/or 62Cu-diacetyl-bis (N4)-methylsemithiocarbazone (62Cu-ATSM) (n=22). All received 18F-fluorodeoxyglucose (18F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. Results: A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of 18F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs (18F-FAZA, p62Cu-ATSM, p18F-FDG. The patients with a higher accumulation had significantly poorer overall survival [18F-FAZA, HR (hazard ratio), 9.50, p62Cu-ATSM, HR, 4.06, p18F-FAZA, HR, 5.28, p62Cu-ATSM, HR, 2.72, p18F-FAZA and 62Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.

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KW - F-fluorodeoxyglucose

KW - Cu-diacetyl-bis (N4)-methylsemithiocarbazone

KW - Hypoxic positron emission tomography

KW - Non-small-cell lung cancer

KW - Prognostic factor

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