18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy

Yushen Qian, Rie Von Eyben, Yufei Liu, Frederick T. Chin, Zheng Miao, Sandeep Apte, Justin N. Carter, Michael S. Binkley, Erqi L. Pollom, Jeremy P. Harris, Nicolas D. Prionas, Madelyn Kissel, Amanda Simmons, Maximilian Diehn, David B. Shultz, J. Martin Brown, Peter G. Maxim, Albert Koong, Edward E. Graves, Billy W. Loo

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Purpose: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. Methods and Materials: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. Results: At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P <.01). Conclusions: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

LanguageEnglish (US)
Pages1183-1192
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume102
Issue number4
DOIs
StatePublished - Nov 15 2018

Fingerprint

hypoxia
Positron-Emission Tomography
radiation therapy
positrons
Radiotherapy
tumors
tomography
Recurrence
Neoplasms
breathing
lungs
Etanidazole
Respiration
Hypoxia
cancer
Nitroimidazoles
oxygenation
Proportional Hazards Models
radiation tolerance
Non-Small Cell Lung Carcinoma

ASJC Scopus subject areas

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

Cite this

18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy. / Qian, Yushen; Von Eyben, Rie; Liu, Yufei; Chin, Frederick T.; Miao, Zheng; Apte, Sandeep; Carter, Justin N.; Binkley, Michael S.; Pollom, Erqi L.; Harris, Jeremy P.; Prionas, Nicolas D.; Kissel, Madelyn; Simmons, Amanda; Diehn, Maximilian; Shultz, David B.; Brown, J. Martin; Maxim, Peter G.; Koong, Albert; Graves, Edward E.; Loo, Billy W.

In: International Journal of Radiation Oncology Biology Physics, Vol. 102, No. 4, 15.11.2018, p. 1183-1192.

Research output: Contribution to journalArticle

Qian, Y, Von Eyben, R, Liu, Y, Chin, FT, Miao, Z, Apte, S, Carter, JN, Binkley, MS, Pollom, EL, Harris, JP, Prionas, ND, Kissel, M, Simmons, A, Diehn, M, Shultz, DB, Brown, JM, Maxim, PG, Koong, A, Graves, EE & Loo, BW 2018, '18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy' International Journal of Radiation Oncology Biology Physics, vol. 102, no. 4, pp. 1183-1192. https://doi.org/10.1016/j.ijrobp.2018.03.045
Qian, Yushen ; Von Eyben, Rie ; Liu, Yufei ; Chin, Frederick T. ; Miao, Zheng ; Apte, Sandeep ; Carter, Justin N. ; Binkley, Michael S. ; Pollom, Erqi L. ; Harris, Jeremy P. ; Prionas, Nicolas D. ; Kissel, Madelyn ; Simmons, Amanda ; Diehn, Maximilian ; Shultz, David B. ; Brown, J. Martin ; Maxim, Peter G. ; Koong, Albert ; Graves, Edward E. ; Loo, Billy W. / 18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy. In: International Journal of Radiation Oncology Biology Physics. 2018 ; Vol. 102, No. 4. pp. 1183-1192.
@article{b94187b65cb4468f85530f3f4e93b6a8,
title = "18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy",
abstract = "Purpose: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. Methods and Materials: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10{\%} on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. Results: At baseline, imageable hypoxia was demonstrated in 43{\%} of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30{\%}) than those without (0{\%}) (P <.01). Conclusions: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40{\%} of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.",
author = "Yushen Qian and {Von Eyben}, Rie and Yufei Liu and Chin, {Frederick T.} and Zheng Miao and Sandeep Apte and Carter, {Justin N.} and Binkley, {Michael S.} and Pollom, {Erqi L.} and Harris, {Jeremy P.} and Prionas, {Nicolas D.} and Madelyn Kissel and Amanda Simmons and Maximilian Diehn and Shultz, {David B.} and Brown, {J. Martin} and Maxim, {Peter G.} and Albert Koong and Graves, {Edward E.} and Loo, {Billy W.}",
year = "2018",
month = "11",
day = "15",
doi = "10.1016/j.ijrobp.2018.03.045",
language = "English (US)",
volume = "102",
pages = "1183--1192",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - 18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy

AU - Qian, Yushen

AU - Von Eyben, Rie

AU - Liu, Yufei

AU - Chin, Frederick T.

AU - Miao, Zheng

AU - Apte, Sandeep

AU - Carter, Justin N.

AU - Binkley, Michael S.

AU - Pollom, Erqi L.

AU - Harris, Jeremy P.

AU - Prionas, Nicolas D.

AU - Kissel, Madelyn

AU - Simmons, Amanda

AU - Diehn, Maximilian

AU - Shultz, David B.

AU - Brown, J. Martin

AU - Maxim, Peter G.

AU - Koong, Albert

AU - Graves, Edward E.

AU - Loo, Billy W.

PY - 2018/11/15

Y1 - 2018/11/15

N2 - Purpose: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. Methods and Materials: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. Results: At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P <.01). Conclusions: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

AB - Purpose: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. Methods and Materials: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. Results: At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P <.01). Conclusions: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

UR - http://www.scopus.com/inward/record.url?scp=85047635605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047635605&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2018.03.045

DO - 10.1016/j.ijrobp.2018.03.045

M3 - Article

VL - 102

SP - 1183

EP - 1192

JO - International Journal of Radiation Oncology Biology Physics

T2 - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 4

ER -