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Title: Pretreatment photosensitizer dosimetry reduces variation in tumor response

Abstract

Purpose: To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment. Methods and Materials: Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. To compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower quartile, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay. Results: Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups. Conclusions: This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency.

Authors:
 [1];  [2];  [1];  [3];  [4];  [1];  [1];  [3];  [5]
  1. Thayer School of Engineering, Dartmouth College, Hanover, NH (United States)
  2. Thayer School of Engineering, Dartmouth College, Hanover, NH (United States) and Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA (United States). E-mail: Brian.W.Pogue@Dartmouth.edu
  3. (United States)
  4. Section of Biostatistics and Epidemiology, Dartmouth Medical School, Hanover, NH (United States)
  5. Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA (United States)
Publication Date:
OSTI Identifier:
20793403
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2005.11.019; PII: S0360-3016(05)02955-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, 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; DOSIMETRY; FLUORESCENCE; NEOPLASMS; PLANNING; RADIATION DOSES; RADIOTHERAPY; UPTAKE

Citation Formats

Zhou Xiaodong, Pogue, Brian W., Chen Bin, Department of Surgery, Dartmouth Medical School, Hanover, NH, Demidenko, Eugene, Joshi, Rohan, Hoopes, Jack, Department of Surgery, Dartmouth Medical School, Hanover, NH, and Hasan, Tayyaba. Pretreatment photosensitizer dosimetry reduces variation in tumor response. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Zhou Xiaodong, Pogue, Brian W., Chen Bin, Department of Surgery, Dartmouth Medical School, Hanover, NH, Demidenko, Eugene, Joshi, Rohan, Hoopes, Jack, Department of Surgery, Dartmouth Medical School, Hanover, NH, & Hasan, Tayyaba. Pretreatment photosensitizer dosimetry reduces variation in tumor response. United States. doi:10.1016/J.IJROBP.2005.1.
Zhou Xiaodong, Pogue, Brian W., Chen Bin, Department of Surgery, Dartmouth Medical School, Hanover, NH, Demidenko, Eugene, Joshi, Rohan, Hoopes, Jack, Department of Surgery, Dartmouth Medical School, Hanover, NH, and Hasan, Tayyaba. Wed . "Pretreatment photosensitizer dosimetry reduces variation in tumor response". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793403,
title = {Pretreatment photosensitizer dosimetry reduces variation in tumor response},
author = {Zhou Xiaodong and Pogue, Brian W. and Chen Bin and Department of Surgery, Dartmouth Medical School, Hanover, NH and Demidenko, Eugene and Joshi, Rohan and Hoopes, Jack and Department of Surgery, Dartmouth Medical School, Hanover, NH and Hasan, Tayyaba},
abstractNote = {Purpose: To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment. Methods and Materials: Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. To compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower quartile, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay. Results: Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups. Conclusions: This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 64,
place = {United States},
year = {Wed Mar 15 00:00:00 EST 2006},
month = {Wed Mar 15 00:00:00 EST 2006}
}
  • Purpose: The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays. Methods: To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation ratesmore » in individual patients. Several constraints have been used in the optimization problem because tumor-volume variation during radiotherapy is described by a sum of exponentials; therefore, the problem of accurately fitting a model to measured data is ill-posed. The model was applied to measured tumor-volume variation curves from a clinical study on tumor-volume variation during radiotherapy for 14 head and neck cancer patients in which an integrated CT/linear particle accelerator (LINAC) system was used for tumor-volume measurements. Results: The two-level cell population tumor-volume modeling is capable of describing tumor-volume variation throughout the entire treatment for 11 of the 14 patients. For three patients, the tumor-volume variation was described only during the initial part of treatment, a fact that may be related to the neglected hypoxia in the two-level approximation. The predicted probability density distribution for the survival fractions agrees with the data obtained using in vitro studies with predictive assays. The mean value 0.35 of survival fraction obtained in this study is larger than the value 0.32 from in vitro studies, which could be expected because of greater repair in vivo. The mean half-life obtained in this study for the head-and-neck squamous cell carcinoma (SCC) is equal to 3.8 mean potential doubling times, which agrees with 4.0 mean potential doubling times obtained previously for lung SCC. Conclusions: The distribution of cell survival fractions obtained in this study support the hypothesis that the tumor-volume variation during radiotherapy treatment for head and neck cancer can be described by the two-level cell population tumor-volume model. This model can be used for in vivo evaluation of patient-specific radiobiological parameters that are needed for tumor-control probability evaluation.« less
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