1. Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome
- Author
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Joseph K. Salama, Karthik Vishwanath, Nimmi Ramanujam, Alaattin Erkanli, James R. Oleson, Fangyao Hu, David M. Brizel, Walter T. Lee, Bercedis Peterson, and Mark W. Dewhirst
- Subjects
Cancer Research ,Metabolic Clearance Rate ,medicine.medical_treatment ,chemistry.chemical_element ,01 natural sciences ,Oxygen ,Article ,010309 optics ,Hemoglobins ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,0103 physical sciences ,Animals ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Oxygen saturation (medicine) ,Radiation ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Head and neck cancer ,Dose-Response Relationship, Radiation ,Radiotherapy Dosage ,Oxygenation ,Tumor Oxygenation ,medicine.disease ,Radiation therapy ,Kinetics ,Treatment Outcome ,Oncology ,chemistry ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Tumor Hypoxia ,Female ,Dose Fractionation, Radiation ,Radiotherapy, Conformal ,Nuclear medicine ,business ,Perfusion ,Blood Flow Velocity - Abstract
Purpose To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. Methods and Materials 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. Results 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. Conclusions 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.
- Published
- 2016
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