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

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/dmore » 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.« less

Authors:
 [1];  [2];  [3];  [4]; ;  [5];  [3];  [4];  [3];  [4];  [4];  [3];  [4];  [1];  [3]
  1. Department of Biomedical Engineering, Duke University, Durham, North Carolina (United States)
  2. Department of Physics, Miami University, Oxford, Ohio (United States)
  3. Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)
  4. (United States)
  5. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States)
Publication Date:
OSTI Identifier:
22645665
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; FRACTIONATED IRRADIATION; GY RANGE 01-10; GY RANGE 10-100; HEAD; MONTE CARLO METHOD; NECK; NEOPLASMS; OXYGEN; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Hu, Fangyao, Vishwanath, Karthik, Salama, Joseph K., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Erkanli, Alaattin, Peterson, Bercedis, Oleson, James R., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Lee, Walter T., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, North Carolina, Brizel, David M., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Ramanujam, Nimmi, and Dewhirst, Mark W., E-mail: mark.dewhirst@duke.edu. Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.06.007.
Hu, Fangyao, Vishwanath, Karthik, Salama, Joseph K., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Erkanli, Alaattin, Peterson, Bercedis, Oleson, James R., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Lee, Walter T., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, North Carolina, Brizel, David M., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Ramanujam, Nimmi, & Dewhirst, Mark W., E-mail: mark.dewhirst@duke.edu. Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome. United States. doi:10.1016/J.IJROBP.2016.06.007.
Hu, Fangyao, Vishwanath, Karthik, Salama, Joseph K., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Erkanli, Alaattin, Peterson, Bercedis, Oleson, James R., Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina, Lee, Walter T., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, North Carolina, Brizel, David M., Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina, Ramanujam, Nimmi, and Dewhirst, Mark W., E-mail: mark.dewhirst@duke.edu. 2016. "Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome". United States. doi:10.1016/J.IJROBP.2016.06.007.
@article{osti_22645665,
title = {Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome},
author = {Hu, Fangyao and Vishwanath, Karthik and Salama, Joseph K. and Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina and Erkanli, Alaattin and Peterson, Bercedis and Oleson, James R. and Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina and Lee, Walter T. and Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina and Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, North Carolina and Brizel, David M. and Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina and Ramanujam, Nimmi and Dewhirst, Mark W., E-mail: mark.dewhirst@duke.edu},
abstractNote = {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.},
doi = {10.1016/J.IJROBP.2016.06.007},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = 2016,
month =
}
  • Purpose: To determine the ability of pharmacokinetic parameters derived from dynamic contrast-enhanced MRI (DCE- MRI) acquired before and during concurrent chemotherapy and radiation therapy to predict clinical response in patients with head and neck cancer. Methods: Eleven patients underwent a DCE-MRI scan at three time points: 1–2 weeks before treatment, 4–5 weeks after treatment initiation, and 3–4 months after treatment completion. Post-processing of MRI data included correction to reduce motion artifacts. The arterial input function was obtained by measuring the dynamic tracer concentration in the jugular veins. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), rate constant (Kep;more » Kep = Ktrans/ve), and plasma volume fraction (vp) were computed for primary tumors and cervical nodal masses. Patients were categorized into two groups based on response to therapy at 3–4 months: responders (no evidence of disease) and partial responders (regression of disease). Responses of the primary tumor and nodes were evaluated separately. A linear classifier and receiver operating characteristic curve analyses were used to determine the best model for discrimination of responders from partial responders. Results: When the above pharmacokinetic parameters of the primary tumor measured before and during treatment were incorporated into the linear classifier, a discriminative accuracy of 88.9%, with sensitivity =100% and specificity = 66.7%, was observed between responders (n=6) and partial responders (n=3) for the primary tumor with the corresponding accuracy = 44.4%, sensitivity = 66.7%, and specificity of 0% for nodal masses. When only pre-treatment parameters were used, the accuracy decreased to 66.7%, with sensitivity = 66.7% and specificity = 66.7% for the primary tumor and decreased to 33.3%, sensitivity of 50%, and specificity of 0% for nodal masses. Conclusion: Higher accuracy, sensitivity, and specificity were obtained using DCE-MRI-derived pharmacokinetic parameters acquired before and during treatment as compared with those derived from the pre-treatment time-point, exclusively.« less
  • Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocolmore » were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.« less
  • The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. The authors describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2--120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N =more » 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In this study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity. 21 refs., 1 tab.« less
  • Purpose: To evaluate the effect of continued cigarette smoking among patients undergoing radiation therapy for head-and-neck cancer by comparing the clinical outcomes among active smokers and quitters. Methods and Materials: A review of medical records identified 101 patients with newly diagnosed squamous cell carcinoma of the head and neck who continued to smoke during radiation therapy. Each active smoker was matched to a control patient who had quit smoking before initiation of radiation therapy. Matching was based on tobacco history (pack-years), primary site, age, sex, Karnofsky Performance Status, disease stage, radiation dose, chemotherapy use, year of treatment, and whether surgicalmore » resection was performed. Outcomes were compared by use of Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer toxicity criteria. Results: With a median follow-up of 49 months, active smokers had significantly inferior 5-year overall survival (23% vs. 55%), locoregional control (58% vs. 69%), and disease-free survival (42% vs. 65%) compared with the former smokers who had quit before radiation therapy (p < 0.05 for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of Grade 3 or greater late complications was also significantly increased among active smokers compared with former smokers (49% vs. 31%, p = 0.01). Conclusions: Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcomes. Further studies analyzing the biologic and molecular reasons underlying these differences are planned.« less
  • After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrentmore » disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional cures than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.« less