Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome.
To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy.



We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model.



First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy.



Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.
: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Fangyao
F
Hu
: Department of Physics, Miami University, Oxford, OH, USA.
Karthik
K
Vishwanath
: Department of Radiation Oncology, Duke University, Durham, NC, USA.|: Division of Radiation Oncology, Veterans Administration Medical Center, Durham, NC.
Joseph K
JK
Salama
: Department of Biostatistics and Bioinformatics, Duke University Medical Center.
Alaattin
A
Erkanli
: Department of Biostatistics and Bioinformatics, Duke University Medical Center.
Bercedis
B
Peterson
: Department of Radiation Oncology, Duke University, Durham, NC, USA.|: Division of Radiation Oncology, Veterans Administration Medical Center, Durham, NC.
James R
JR
Oleson
: Department of Radiation Oncology, Duke University, Durham, NC, USA.|: Division of Head and Neck Surgery & Communicative Sciences, Duke University Medical Center, Durham, NC.|: Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, NC.
Walter T
WT
Lee
: Department of Radiation Oncology, Duke University, Durham, NC, USA.|: Division of Head and Neck Surgery & Communicative Sciences, Duke University Medical Center, Durham, NC.
David M
DM
Brizel
: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Nimmi
N
Ramanujam
: Department of Radiation Oncology, Duke University, Durham, NC, USA.
Mark W
MW
Dewhirst
D000818:Animals; D001783:Blood Flow Velocity / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate / Q000528:radiation effects; D051379:Mice; D010100:Oxygen / Q000097:blood*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D000072258:Tumor Hypoxia / Q000528:radiation effects*
D006454:Hemoglobins; D010100:Oxygen