title: Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol.
abstract: BACKGROUND
  Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation.
  
  
  METHODS
  The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1stand 5thweek (cisplatin 20 mg/m2/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start.
  
  
  CONCLUSIONS
  The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.
authors.affiliation: Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany. steffi.pigorsch@tum.de.|Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany. steffi.pigorsch@tum.de.
authors.forename: Steffi U
authors.initials: SU
authors.lastname: Pigorsch
authors.affiliation: Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.|Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Wilkens
authors.affiliation: Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.|Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany.
authors.forename: Severin
authors.initials: S
authors.lastname: Kampfer
authors.affiliation: Institute of Medical Statistics and Epidemiology (IMSE), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Kehl
authors.affiliation: Institute of Medical Statistics and Epidemiology (IMSE), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hapfelmeier
authors.affiliation: Münchner Studienzentrum (MSZ Coordination Centre for Clinical Trials), Technical University of Munich, Ismaninger Strasse 22, D-81675, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schläger
authors.affiliation: Department of Ear, Neck and Throat (ENT), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Bier
authors.affiliation: Department of Nuclear Medicine, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.|Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000072258:Tumor Hypoxia; D055815:Young Adult
keywords: Chemo-irradiation; Dose escalation; Head and neck cancer; Randomized prospective trial