title: Dose escalation for locally advanced lung cancer using adaptive radiation therapy with simultaneous integrated volume-adapted boost.
abstract: OBJECTIVE
  To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer.
  
  
  METHODS
  Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2).
  
  
  RESULTS
  The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase.
  
  
  CONCLUSIONS
  The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA. eweiss@mcvh-vcu.edu
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Weiss
authors.forename: Mirek
authors.initials: M
authors.lastname: Fatyga
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Nesrin
authors.initials: N
authors.lastname: Dogan
authors.forename: Salim
authors.initials: S
authors.lastname: Balik
authors.forename: William
authors.initials: W
authors.lastname: Sleeman
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hugo
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D017321:Clinical Trials, Phase I as Topic; D005240:Feasibility Studies; D056973:Four-Dimensional Computed Tomography / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects*; D011446:Prospective Studies; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D047368:Tumor Burden / Q000528:radiation effects