title: Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer.
abstract: BACKGROUND
  Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia.
  
  
  METHODS
  The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment.
  
  
  RESULTS
  The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy).
  
  
  CONCLUSIONS
  This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting.
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. h.crezee@amc.uva.nl.
authors.forename: J
authors.initials: J
authors.lastname: Crezee
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. c.m.vanleeuwen@amc.uva.nl.
authors.forename: C M
authors.initials: CM
authors.lastname: van Leeuwen
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.l.oei@amc.uva.nl.|Laboratory for Experimental Oncology and Radiobiology (LEXOR)/Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.l.oei@amc.uva.nl.
authors.forename: A L
authors.initials: AL
authors.lastname: Oei
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. l.e.vanheerden@amc.uva.nl.
authors.forename: L E
authors.initials: LE
authors.lastname: van Heerden
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.bel@amc.uva.nl.
authors.forename: A
authors.initials: A
authors.lastname: Bel
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. l.stalpers@amc.uva.nl.
authors.forename: L J A
authors.initials: LJ
authors.lastname: Stalpers
authors.affiliation: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. pirus.ghadjar@charite.de.
authors.forename: P
authors.initials: P
authors.lastname: Ghadjar
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. n.a.franken@amc.uva.nl.|Laboratory for Experimental Oncology and Radiobiology (LEXOR)/Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. n.a.franken@amc.uva.nl.
authors.forename: N A P
authors.initials: NA
authors.lastname: Franken
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. h.p.kok@amc.uva.nl.
authors.forename: H P
authors.initials: HP
authors.lastname: Kok
mesh_terms: D002986:Clinical Trials as Topic; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D016014:Linear Models; D011838:Radiation-Sensitizing Agents / Q000737:chemistry; D011857:Radiographic Image Interpretation, Computer-Assisted; D011878:Radiotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D013696:Temperature; D014057:Tomography, X-Ray Computed; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents
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