title: Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22).
abstract: OBJECTIVE
  To assess the results of a multi-institutional study of intensity-modulated radiation therapy (IMRT) for early oropharyngeal cancer.
  
  
  METHODS
  Patients with oropharyngeal carcinoma Stage T1-2, N0-1, M0 requiring treatment of the bilateral neck were eligible. Chemotherapy was not permitted. Prescribed planning target volumes (PTVs) doses to primary tumor and involved nodes was 66 Gy at 2.2 Gy/fraction over 6 weeks. Subclinical PTVs received simultaneously 54-60 Gy at 1.8-2.0 Gy/fraction. Participating institutions were preapproved for IMRT, and quality assurance review was performed by the Image-Guided Therapy Center.
  
  
  RESULTS
  69 patients were accrued from 14 institutions. At median follow-up for surviving patients (2.8 years), the 2-year estimated local-regional failure (LRF) rate was 9%. 2/4 patients (50%) with major underdose deviations had LRF compared with 3/49 (6%) without such deviations (p = 0.04). All cases of LRF, metastasis, or second primary cancer occurred among patients who were current/former smokers, and none among patients who never smoked. Maximal late toxicities Grade >or=2 were skin 12%, mucosa 24%, salivary 67%, esophagus 19%, osteoradionecrosis 6%. Longer follow-up revealed reduced late toxicity in all categories. Xerostomia Grade >or=2 was observed in 55% of patients at 6 months but reduced to 25% and 16% at 12 and 24 months, respectively. In contrast, salivary output did not recover over time.
  
  
  CONCLUSIONS
  Moderately accelerated hypofractionatd IMRT without chemotherapy for early oropharyngeal cancer is feasible, achieving high tumor control rates and reduced salivary toxicity compared with similar patients in previous Radiation Therapy Oncology Group studies. Major target underdose deviations were associated with higher LRF rate.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. eisbruch@umich.edu
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.forename: Clifford K S
authors.initials: CK
authors.lastname: Chao
authors.forename: William
authors.initials: W
authors.lastname: Straube
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sanguineti
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.forename: Walter R
authors.initials: WR
authors.lastname: Bosch
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011786:Quality Control; D011832:Radiation Injuries / Q000473:pathology; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods* / Q000592:standards; D047368:Tumor Burden