title: Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy.
abstract: BACKGROUND
  The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system).
  
  
  METHODS
  This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity.
  
  
  RESULTS
  Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade > or =3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images.
  
  
  CONCLUSIONS
  The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction.
authors.affiliation: Department of Radiation Oncology, Oncology Center, Brussels University Hospital, Brussels, Belgium. samuel.bral@uzbrussel.be
authors.forename: Samuel
authors.initials: S
authors.lastname: Bral
authors.forename: Michaël
authors.initials: M
authors.lastname: Duchateau
authors.forename: Harijati
authors.initials: H
authors.lastname: Versmessen
authors.forename: Douwe
authors.initials: D
authors.lastname: Verdries
authors.forename: Benedikt
authors.initials: B
authors.lastname: Engels
authors.forename: Mark
authors.initials: M
authors.lastname: De Ridder
authors.forename: Koen
authors.initials: K
authors.lastname: Tournel
authors.forename: Christine
authors.initials: C
authors.lastname: Collen
authors.forename: Hendrik
authors.initials: H
authors.lastname: Everaert
authors.forename: Denis
authors.initials: D
authors.lastname: Schallier
authors.forename: Jacques
authors.initials: J
authors.lastname: De Greve
authors.forename: Guy
authors.initials: G
authors.lastname: Storme
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011832:Radiation Injuries; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy / Q000009:adverse effects / Q000379:methods*