title: Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer.
abstract: The CONTRAST (CONventional vs.Tumor Recurrence Adapted Specification of Target dose) phase I trial tested the safety of FDG PET guided dose redistribution in patients receiving accelerated chemo-radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC).
  
  
  
  CONTRAST was designed with two pre-defined dose-escalation steps to the FDG PET-avid volume (GTVPET). The primary end point was any early grade 4+ toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). The dose to GTVPET was escalated to a uniform prescription of 82Gy EQD2 in the first step. All patients received accelerated radiotherapy (6 fractions a week) delivering 34 fractions of 2.34Gy to the GTVPET as well as concomitant weekly cisplatin. Inclusion criteria were (1) primary SCC of oral cavity, oro- or hypo-pharynx, or laynx, (2) candidates for concomitant chemo-radiotherapy and (3) p16 negative tumors or p16 positive tumors in patients with smoking history of >10 pack years. GTVPET was defined by a specialist in nuclear medicine and a radiologist, while the anatomic GTV was defined in collaboration between an oncologist and a radiologist.
  
  
  
  Median follow up time from the end of treatment was 18months (range 7-21months). All 15 patients completed treatment without interruptions and no incidents of early grade 4+ toxicity were observed. Four patients had ulceration at the evaluation two months after treatment, two have subsequently healed, but two remain, raising concerns regarding late effects.
  
  
  
  With all 15 cases having completed four month follow up and no incidence of early grade 4+ toxicity FDG PET based dose escalation to 82Gy passed the protocol-defined criterion for dose escalation. However, two cases of concern regarding late outcome led us to refrain from further dose escalation and proceed with the current dose level in a larger comparative effectiveness trial.
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark. Electronic address: jacobrasmu@gmail.com.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Rasmussen
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Katrin
authors.initials: K
authors.lastname: Håkansson
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Vogelius
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Aznar
authors.affiliation: Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, University of Copenhagen, Denmark.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Fischer
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Friborg
authors.affiliation: Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, University of Copenhagen, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Loft
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Claus A
authors.initials: CA
authors.lastname: Kristensen
authors.affiliation: Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002945:Cisplatin
keywords: Dose painting; FDG PET; Squamous cell carcinoma of the head and neck