title: Dose escalation model for limited-stage small-cell lung cancer.
abstract: OBJECTIVE
  To construct a model for the local dose-response relationship of limited-stage small-cell lung cancer (LS-SCLC) along with subsequent models for dose-per-fraction escalation.
  
  
  METHODS
  Reported doses and 2-year progression free survival (PFS(2year)) rates from LS-SCLC studies were used to construct a dose-response model. Modeling incorporated effects of chemotherapy, incomplete repair of sublethal damage and variations in both kick-off time for rapid reproliferation and effective tumor cell doubling time. Response was modeled as a function of overall treatment duration in order to shed light on the optimum radiotherapy treatment duration. Subsequent models were constructed for more aggressive radiotherapy by means of dose-per-fraction escalation for once a day (QD) and twice a day (BID) fractionation schedules.
  
  
  RESULTS
  Modeling response as a function of treatment duration resulted in an optimum treatment duration of 3 weeks for both fractionation schedules. Modeling for dose-per-fraction escalation resulted in an increase in the expected local PFS(2year) for both fractionation schedules with possible gains in a BID schedule with lower expected late complication rates than a QD schedule yielding the same expected local PFS(2year).
  
  
  CONCLUSIONS
  This modeling suggests more aggressive treatment through escalation of dose-per-fraction, which may result in substantial gains in local PFS(2year). This points towards treatment durations of 3 weeks as being optimal with a BID schedule predicting possible gains in local PFS(2year) at lower rates of expected late complications than a QD schedule.
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison, WI 53792, USA.
authors.forename: Noah B
authors.initials: NB
authors.lastname: Arvidson
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuntia
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tomé
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D015233:Models, Statistical; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents