title: Analysis of mandibular dose distribution in radiotherapy for oropharyngeal cancer: dosimetric and clinical results in 18 patients.
abstract: OBJECTIVE
  The relationship between the radiation dose and the risk of the osteoradionecrosis is well known. However, the dose to the mandible is not routinely assessed in the radiotherapy for head and neck cancer. The aim of our study was to analyze the mandibular dose distribution in the patients administered curative radiotherapy for squamous cell carcinoma of the oropharynx. Moreover, the clinical results have been analyzed.
  
  
  METHODS
  We examined the clinical records and treatment plans in 18 patients treated with bifractionated radiotherapy for stage II-IV oropharyngeal cancer. In 17 patients, the total radiotherapy dose prescribed in the International Committee of Radiation Units and Measurements (ICRU) reference point was 74.4 Gy administered in 62 fractions (1.2 Gy twice daily with 6h interfraction interval) and one patient received a dose of 75.6 Gy. The whole dose to the mandibular-orophryngeal region was delivered with 6 MV photons. The mandible was contoured manually on computed tomographic scans and the point doses at the both mandibular condyles, ascending ramus, mental symphysis, molar and retromolar regions were assessed. Moreover, the cumulative dose-volume histograms (DHVs) were evaluated. The median follow-up period for alive patients is 30 months (range, 21-44+ months).
  
  
  RESULTS
  Tumor remission was observed in 17 patients: in 11 cases, complete remission was achieved and in six cases, only partial remission was possible. One patient was lost to follow-up before the first response evaluation. The median survival for all patients is 22 months (range, 3-44+ months). Ten patients are alive and seven died. In six cases, the cause of death was head and neck tumor and in one died due to pancreatic cancer (second primary). No late bone post-radiation complication was seen. The highest radiotherapy doses were observed in the retromolar regions. The mean percentage doses at the right and left retromolar regions were 101.3+/-3.8% (range, 90.2-109.1%) and 101.7+/-2.5% (range, 95.2-105.8%), respectively. Lower doses were seen in ascending ramus (the mean percentage doses at right and left ascending ramus were 97.3+/-8.5% and 97.8+/-7.6%, respectively), the molar regions (the mean percentage doses at right and left molar regions were 86.0+/-13.5% and 88.1+/-12.9%, respectively), and at the mandibular condyles (the mean percentage doses at the right and left mandibular condyles were 72.6+/-18% and 77.0+/-16.5%, respectively). The volume of the mandible ranged from 60.1 to 110.1cm(3) (a mean of of 82.3 cm(3)). In all patients, the maximum dose absorbed in the mandible was higher than the dose prescribed in the ICRU point and the mean maximum dose absorbed in the mandible was 105.7+/-2.1% (range, 102.4-110.6%). The percentage of mandibular volume receiving a dose higher than prescribed was 28.6+/-14.9% (range 10.2-58.1%). The area underlying the DVH curve, the maximum mandibular doses and the retromolar doses did not appear to statistically depend on use of wedge or mandibular volume.
  
  
  CONCLUSIONS
  Radiotherapy for oropharyngeal cancer is associated with high doses to the retromolar mandibular regions (the dose can be higher than prescribed in the ICRU reference point), ascending ramus and molar regions. Lower doses are absorbed at the condyles and mental symphysis. The single dose point (for example, the ICRU reference point) could be not used as a representative for the mandibular dose. In our small series of patients treated with hyperfractionated irradiation, these dose heterogeneities were not correlated to the patient- and treatment-related factors and are not related to the increased risk of late bone complications. The clinical relevance of mandibular dose distribution remains to be established in larger series of patients treated with conventionally and unconventionally fractionated irradiation.
authors.affiliation: Division of Radiation Oncology, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Jereczek-Fossa
authors.forename: Cristina
authors.initials: C
authors.lastname: Garibaldi
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Catalano
authors.forename: Alberto
authors.initials: A
authors.lastname: d'Onofrio
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Pas
authors.forename: Chiara
authors.initials: C
authors.lastname: Bocci
authors.forename: Mario
authors.initials: M
authors.lastname: Ciocca
authors.forename: Fiora
authors.initials: F
authors.lastname: DePaoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008334:Mandible / Q000528:radiation effects*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D010025:Osteoradionecrosis / Q000517:prevention & control; D011446:Prospective Studies; D011829:Radiation Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome