title: Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  The local control of inoperable non-small cell lung cancer (NSCLC) using standard radiotherapy (RT) doses is inadequate. Dose escalation is a potential strategy to improve the local control for patients with NSCLC; however, the optimal dose required for local control in this setting is unknown.
  
  
  METHODS
  Patients with unresectable or inoperable stage II/III NSCLC with ECOG≤1 received 48 Gy in 20 daily fractions using intensity-modulated radiotherapy, followed by 1 of 3 boost dose levels: 16.8 Gy/7 (cumulative 2 Gy equivalent dose [EQD2]≅76 Gy/38), 20.0 Gy/7 (EQD2≅84 Gy/42), and 22.7 Gy/7 (EQD2≅92 Gy/46). Two cycles of cisplatin/etoposide chemotherapy were given concurrent with RT. The maximum tolerated dose was defined as the dose at which ≥30% experienced dose-limiting toxicity (any NCIC Common Terminology for Adverse Events V3.0 grade 3 or higher acute toxicity).
  
  
  RESULTS
  Twelve patients completed treatment with a median follow-up of 22 months (range, 7 to 48). The median age was 72 (range, 54 to 80) and 50% of patients had adenocarcinoma. Five, 3, and 4 patients were treated on dose levels 1, 2, and 3, respectively. No dose-limiting toxicity was observed. One-year local progression-free survival and overall survival estimates were 81% and 58%, respectively.
  
  
  CONCLUSIONS
  Hypofractionated intensity-modulated radiotherapy was well tolerated and provided meaningful local control for patients with locally advanced inoperable NSCLC. The maximum tolerated dose of RT in this setting lies beyond an EQD2 of 92 Gy/46 and further dose escalation in this setting is warranted.
authors.affiliation: *Department of Oncology, Division of Radiation Oncology †Department of Oncology, Division of Medical Oncology ‡Division of Medical Physics, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: Julian O
authors.initials: JO
authors.lastname: Kim
authors.forename: Karen P
authors.initials: KP
authors.lastname: Chu
authors.forename: Alysa
authors.initials: A
authors.lastname: Fairchild
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.forename: Charles
authors.initials: C
authors.lastname: Butts
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Gabos
authors.forename: Anil A
authors.initials: AA
authors.lastname: Joy
authors.forename: Tirath
authors.initials: T
authors.lastname: Nijjar
authors.forename: Donald M
authors.initials: DM
authors.lastname: Robinson
authors.forename: Randeep
authors.initials: R
authors.lastname: Sangha
authors.forename: Rufus
authors.initials: R
authors.lastname: Scrimger
authors.forename: Micheal
authors.initials: M
authors.lastname: Smylie
authors.forename: Don
authors.initials: D
authors.lastname: Yee
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069473:Radiation Dose Hypofractionation; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D005047:Etoposide; D002945:Cisplatin