title: Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases.
abstract: OBJECTIVE
  Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring.
  
  
  METHODS
  We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression.
  
  
  RESULTS
  Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model.
  
  
  CONCLUSIONS
  Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.
authors.affiliation: Department of Radiation Oncology, Leopoldina Hospital Schweinfurt, Schweinfurt, Germany. Electronic address: rainer_klement@gmx.de.
authors.forename: Rainer J
authors.initials: RJ
authors.lastname: Klement
authors.affiliation: Department of Radiation Oncology, Barmherzige Brüder, Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Allgäuer
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Radiation Oncology, University Medicine Rostock, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Andratschke
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Blanck
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Judit
authors.initials: J
authors.lastname: Boda-Heggemann
authors.affiliation: Department of Radiation Oncology, Allgemeines Krankenhaus Wien, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.affiliation: Department of Radiation Oncology, Technical University Munich, Munich, Germany.
authors.forename: Marciana
authors.initials: M
authors.lastname: Duma
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Ernst
authors.affiliation: Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
authors.affiliation: Department of Radiation Oncology, LMU München, Munich, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Ganswindt
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Magdeburg, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hass
authors.affiliation: Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Henkenberens
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Frankfurt am Main, Frankfurt, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Imhoff
authors.affiliation: Department of Radiation Oncology, Klinikum Augsburg, Augsburg, Germany.
authors.forename: Henning K
authors.initials: HK
authors.lastname: Kahl
authors.affiliation: Department of Radiation Oncology, Helios Klinikum Berlin Buch, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Krempien
authors.affiliation: Department of Radiation Oncology, Medical Faculty and University Hospital C.G. Carus, Technische Universität Dresden, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Lohaus
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Nestle
authors.affiliation: Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Meinhard
authors.initials: M
authors.lastname: Nevinny-Stickel
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Aachen, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Schmitt
authors.affiliation: Department of Radiation Oncology, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Semrau
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Sterzing
authors.affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Streblow
authors.affiliation: Department of Radiation Oncology, University Hospital Jena, Jena, Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wendt
authors.affiliation: Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wittig
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Guckenberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D002648:Child; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008962:Models, Theoretical; D009364:Neoplasm Recurrence, Local; D016012:Poisson Distribution; D011336:Probability; D016634:Radiosurgery / Q000379:methods*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult