Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome

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.

Influence of Radiotherapy Fractionation Schedule on the Tumor Vascular Microenvironment in Prostate and Lung Cancer Models

“…In the LLC model with rapid repopulation, the perfusion increase after 2 × 12 Gy was limited in time (3-7 days). Of note, other studies [10] and other experiments in our hands [9] have been able to observe this up to 7 days, probably because of variations in tumor growth rate. Yet, our data show that perfusion and hypoxia were affected, at least partially, in proportion with tumor control, consistent with previous reports [12].…”

“…Increased pericyte coverage has been shown after fractionated RT, with some evidence for contribution of bone-marrow-derived cells [6][7][8][9]11]. However, observations after high dose RT were more heterogeneous [10,13,14,19]. Whether there is a relationship between dose-per-fraction and perivascular coverage had not been investigated in comparable settings [17].…”

Optical and x-ray technology synergies enabling diagnostic and therapeutic applications in medicine

“…As shown in Fig. 4, these include fiber optic-based dosimetry exploiting scintillation detection, 31 online monitoring of tissue oxygenation status using hemoglobin spectroscopy 48 and, more recently, imaging the Cherenkov light generated in tissue by high-energy secondary electrons from MV x-ray beams during treatment. This last approach enables the irradiated tissue surface area to be directly visualized in real time and so is a promising addition to existing tools for quality control and precision x-ray dose delivery.…”

Diffuse Reflectance Spectroscopy reveals heat stress-induced changes in hemoglobin profile in chicken breast

“…These applications have spanned early cancer detection in several organs including skin [13] and breast [14], identification of surgical margins [15], and monitoring response to therapy [16][17][18].…”