TY - JOUR

T1 - Oxygen-Guided Radiation Therapy

AU - Epel, Boris

AU - Maggio, Matthew C.

AU - Barth, Eugene D.

AU - Miller, Richard C.

AU - Pelizzari, Charles A.

AU - Krzykawska-Serda, Martyna

AU - Sundramoorthy, Subramanian V.

AU - Aydogan, Bulent

AU - Weichselbaum, Ralph R.

AU - Tormyshev, Victor M.

AU - Halpern, Howard J.

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Purpose: It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. Methods and Materials: For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. Results: We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P =.04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. Conclusions: This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.

AB - Purpose: It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. Methods and Materials: For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. Results: We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P =.04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. Conclusions: This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.

KW - SQUAMOUS-CELL CARCINOMA

KW - TUMOR HYPOXIA

KW - IN-VIVO

KW - RADIOTHERAPY

KW - CANCER

KW - HEAD

KW - PET

KW - RADICALS

KW - NECK

KW - HETEROGENEITY

UR - http://www.scopus.com/inward/record.url?scp=85059533908&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2018.10.041

DO - 10.1016/j.ijrobp.2018.10.041

M3 - Article

C2 - 30414912

AN - SCOPUS:85059533908

VL - 103

SP - 977

EP - 984

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 4

ER -