title: Adaptive radiotherapy for locally advanced non-small-cell lung cancer does not underdose the microscopic disease and has the potential to increase tumor control.
abstract: OBJECTIVE
  To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP).
  
  
  METHODS
  In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models.
  
  
  RESULTS
  Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% ± 10% to 73% ± 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART.
  
  
  CONCLUSIONS
  Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40% compared with radiotherapy planning without ART.
authors.affiliation: Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg, Germany. guckenberger_m@klinik.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Guckenberger
authors.forename: Anne
authors.initials: A
authors.lastname: Richter
authors.forename: Juergen
authors.initials: J
authors.lastname: Wilbert
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
authors.forename: Mike
authors.initials: M
authors.lastname: Partridge
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods*; D012074:Remission Induction; D012189:Retrospective Studies; D047368:Tumor Burden / Q000528:radiation effects*