Oxygen and perfusion kinetics in response to fractionated radiotherapy in FaDu head and neck cancer xenografts are related to treatment outcome

• Published in: International journal of radiation oncology, biology, physics Vol. 96; no. 2; pp. 462 - 469
• Main Authors: Hu, Fangyao, Vishwanath, Karthik, Salama, Joseph K, Erkanli, Alaattin, Peterson, Bercedis, Oleson, James R, Lee, Walter T, Brizel, David M, Ramanujam, Nimmi, Dewhirst, Mark W
• Format: Journal Article
• Language: English
• Published: 14.06.2016
• Subjects: Hematology, Oncology and Palliative Medicine; Radiology; Hypoxia; Optical spectroscopy; Treatment Response; Reoxygenation; Radiotherapy; FaDu
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2016.06.007

Abstract Purpose Test if oxygenation kinetics correlate with the likelihood for local tumor control following fractionated radiotherapy. Methods and Materials We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration ([THb]) associated with radiotherapy of 5 daily fractions (7.5, 9 or 13.5 Gy/day) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiotherapy. Oxygen saturation (SO2 ) and [THb] were computed using an inverse Monte Carlo model. Results (1) Oxygenation kinetics during and after radiotherapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiotherapy (days 12-15) compared with tumors that recurred locally. (2) Within the group of tumors that recurred, faster increases in oxygenation during radiotherapy (days 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operator curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. (3) The rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/day did not initiate an increase in oxygenation whereas 13.5 Gy/day triggered significant increases in oxygenation during and after radiotherapy. 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 radiotherapy.