Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography

Implications for improvement of therapy schedules

Dong Wook Nathan Kim, Jessica Huamani, Kenneth J. Niermann, Haakil Lee, Ling Geng, Lauren L. Leavitt, Richard A. Baheza, Cameron C. Jones, Shiv Tumkur, Thomas E. Yankeelov, Arthur C. Fleischer, Dennis E. Hallahan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective. Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. Methods. Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. Results. A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P = .016). Conclusions. This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.

Original languageEnglish (US)
Pages (from-to)1507-1517
Number of pages11
JournalJournal of Ultrasound in Medicine
Volume25
Issue number12
StatePublished - Dec 2006

Fingerprint

Doppler Ultrasonography
schedules
therapy
Appointments and Schedules
tumors
Radiation
radiation
Neoplasms
blood flow
Therapeutics
Ionizing Radiation
ionizing radiation
dosage
radiation therapy
Radiotherapy
recovery
Lewis Lung Carcinoma
apoptosis
Microvessels
Tumor Burden

Keywords

  • Radiation therapy
  • Sonography
  • Stereotactic radiation therapy
  • Tumor vasculature

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

Cite this

Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography : Implications for improvement of therapy schedules. / Kim, Dong Wook Nathan; Huamani, Jessica; Niermann, Kenneth J.; Lee, Haakil; Geng, Ling; Leavitt, Lauren L.; Baheza, Richard A.; Jones, Cameron C.; Tumkur, Shiv; Yankeelov, Thomas E.; Fleischer, Arthur C.; Hallahan, Dennis E.

In: Journal of Ultrasound in Medicine, Vol. 25, No. 12, 12.2006, p. 1507-1517.

Research output: Contribution to journalArticle

Kim, DWN, Huamani, J, Niermann, KJ, Lee, H, Geng, L, Leavitt, LL, Baheza, RA, Jones, CC, Tumkur, S, Yankeelov, TE, Fleischer, AC & Hallahan, DE 2006, 'Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: Implications for improvement of therapy schedules', Journal of Ultrasound in Medicine, vol. 25, no. 12, pp. 1507-1517.
Kim, Dong Wook Nathan ; Huamani, Jessica ; Niermann, Kenneth J. ; Lee, Haakil ; Geng, Ling ; Leavitt, Lauren L. ; Baheza, Richard A. ; Jones, Cameron C. ; Tumkur, Shiv ; Yankeelov, Thomas E. ; Fleischer, Arthur C. ; Hallahan, Dennis E. / Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography : Implications for improvement of therapy schedules. In: Journal of Ultrasound in Medicine. 2006 ; Vol. 25, No. 12. pp. 1507-1517.
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abstract = "Objective. Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. Methods. Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. Results. A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P = .016). Conclusions. This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.",
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T1 - Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography

T2 - Implications for improvement of therapy schedules

AU - Kim, Dong Wook Nathan

AU - Huamani, Jessica

AU - Niermann, Kenneth J.

AU - Lee, Haakil

AU - Geng, Ling

AU - Leavitt, Lauren L.

AU - Baheza, Richard A.

AU - Jones, Cameron C.

AU - Tumkur, Shiv

AU - Yankeelov, Thomas E.

AU - Fleischer, Arthur C.

AU - Hallahan, Dennis E.

PY - 2006/12

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N2 - Objective. Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. Methods. Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. Results. A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P = .016). Conclusions. This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.

AB - Objective. Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. Methods. Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. Results. A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P = .016). Conclusions. This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.

KW - Radiation therapy

KW - Sonography

KW - Stereotactic radiation therapy

KW - Tumor vasculature

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