title: Quantifying the combined effect of radiation therapy and hyperthermia in terms of equivalent dose distributions.
abstract: OBJECTIVE
  To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia.
  
  
  METHODS
  Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy(-1)) and β (Gy(-2)) of the linear-quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear-quadratic model.
  
  
  RESULTS
  The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma.
  
  
  CONCLUSIONS
  A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: H.P.Kok@amc.uva.nl.
authors.forename: H Petra
authors.initials: HP
authors.lastname: Kok
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Crezee
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory for Experimental Oncology and Radiobiology (LEXOR)/Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nicolaas A P
authors.initials: NA
authors.lastname: Franken
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lukas J A
authors.initials: LJ
authors.lastname: Stalpers
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology (LEXOR)/Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gerrit W
authors.initials: GW
authors.lastname: Barendsen
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Bel
mesh_terms: D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D006979:Hyperthermia, Induced / Q000295:instrumentation / Q000379:methods*; D016014:Linear Models; D008954:Models, Biological; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*