title: Challenges in radiobiological modeling: can we decide between LQ and LQ-L models based on reviewed clinical NSCLC treatment outcome data?
abstract: OBJECTIVE
  To study the dose-response of stage I non-small-cell lung cancer (NSCLC) in terms of long-term local tumor control (LC) after conventional and hypofractionated photon radiotherapy, modeled with the linear-quadratic (LQ) and linear-quadratic-linear (LQ-L) approaches and to estimate the clinical α/β ratio within the LQ frame.
  
  
  METHODS
  We identified studies of curative radiotherapy as single treatment through MedLine search reporting 3-year LC as primary outcome of interest. Logistic models coupled with the biologically effective dose (BED) at isocenter and PTV edge according to both the LQ and LQ-L models with α/β = 10 Gy were fitted. Additionally, α/β was estimated from direct LQ fits.
  
  
  RESULTS
  Thirty one studies were included reporting outcome of 2319 patients. The LQ-L fit yielded a significant value of 11.0 ± 5.2 Gy for the dose threshold (Dt) for BED10 at the isocenter. The LQ and LQ-L fits did not differ substantially. Concerning the estimation of α/β, the value obtained from the direct LQ fit for the complete fractionation range was 3.9 [68 % CI: 2.2-9.0] Gy (p > 0.05).
  
  
  CONCLUSIONS
  Both LQ and LQ-L fits can model local tumor control after conventionally and hypofractionated irradiation and are robust methods for predicting clinical effects. The observed dose-effect for local control in NSCLC is weaker at high doses due to data dispersion. For BED10 values of 100-150 Gy in ≥3 fractions, the differences in isoeffects predicted by both models can be neglected.
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Hospital Giessen and Marburg, Philipps-University Marburg, Baldingerstrasse, Marburg, 35043, Germany. santiago@staff.uni-marburg.de.
authors.forename: Alina
authors.initials: A
authors.lastname: Santiago
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Hospital Giessen and Marburg, Philipps-University Marburg, Baldingerstrasse, Marburg, 35043, Germany.|Present address: Gemeinschaftspraxis Strahlentherapie am St. Agnes Hospital, Bocholt, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Barczyk
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Hospital Giessen and Marburg, Philipps-University Marburg, Baldingerstrasse, Marburg, 35043, Germany.|Present address: Marburger Ionenstrahl-Therapiezentrum MIT, Marburg, Germany.
authors.forename: Urszula
authors.initials: U
authors.lastname: Jelen
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Hospital Giessen and Marburg, Philipps-University Marburg, Baldingerstrasse, Marburg, 35043, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhart-Cabillic
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Hospital Giessen and Marburg, Philipps-University Marburg, Baldingerstrasse, Marburg, 35043, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wittig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016014:Linear Models; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008875:Middle Aged; D008962:Models, Theoretical; D017785:Photons / Q000627:therapeutic use; D011853:Radiobiology; D011874:Radiometry; D016634:Radiosurgery / Q000379:methods; D011878:Radiotherapy / Q000379:methods*; D016896:Treatment Outcome
keywords: Alpha-beta ratio; Biologically effective dose; Dose-response modeling; Linear-quadratic model; Non-small cell lung cancer