title: Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose.
abstract: OBJECTIVE
  To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  All T1 and T2 (nasal infiltration) NPC treated with a curative intent from 1984 to 1996 were analyzed (n = 509). One hundred sixty-three patients were given ICT after radical external radiotherapy (ERT) (Group A). They were compared with 346 patients treated by ERT alone (Group B). The ERT delivered the tumoricidal dose (uncorrected BED-10 > or =75 Gy) to the primary tumor and did not differ between the two groups in technique or dosage. The ICT delivered a dose of 18-24 Gy in 3 fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. ICT was used to treat local persistence diagnosed at 4-6 weeks after ERT (n = 101) or as an adjuvant for the complete responders to ERT (n = 62).
  
  
  RESULTS
  The two groups did not differ in patients' age or sex, rate of distant metastasis, rate of regional failure, overall survival, or the follow-up duration. However, Group A had significantly more T2 lesions and Group B had significantly more advanced N-stages. Local failure was significantly less (crude rates 6.75% vs. 13.0%; 5-year actuarial rates 5.40% vs. 10.3%) and the disease-specific mortality was significantly lower (crude rates 14.1% vs. 21.7%; 5-year actuarial rates 11.9% vs. 16.4%) in Group A compared to Group B. Multivariate analysis showed that the ICT was the only significant prognostic factor predictive for fewer local failures (Cox regression p = 0.0328, risk ratio = 0.49, 95% confidence interval (95% CI) = 0.256-0.957). However, when ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumor repopulation during the period of radiotherapy became significant in predicting ultimate local failure rate. The two groups were comparable in the incidence rates of each individual chronic radiation complication and the actuarial cumulative rate of the chronic radiation complications, with the exception of chronic radiation nasopharyngeal ulceration/necrosis which occurred in 10 patients in Group A and 1 patient in Group B. Headache (n = 4) and foul smell (n = 8) consequential to ulceration/necrosis were mild and manageable by conservative means. A significant dose-tumor-control relationship existed when local failure was studied as a function of the total physical dose or the total biological equivalent dose (linear quadratic equation, alpha/beta = 10) uncorrected for tumor repopulation during the time course of the radiotherapy.
  
  
  CONCLUSIONS
  Supplementing ERT which delivered tumoricidal dose (uncorrected BED-10 > or =75 Gy), ICT significantly enhanced ultimate local control and avoided the necessity for morbid salvage treatments in early T-stage (T1/T2 nasal infiltration) NPC. The slight increase in chronic radiation ulceration/necrosis after ICT was acceptable with mild and manageable symptoms. Other late complications were not increased. A significant dose-tumor-control relationship exists above the conventional tumoricidal dose level.
authors.affiliation: Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong, China. teoml@ha.org.hk
authors.forename: P M
authors.initials: PM
authors.lastname: Teo
authors.forename: S F
authors.initials: SF
authors.lastname: Leung
authors.forename: W Y
authors.initials: WY
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Zee
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001918:Brachytherapy / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D004844:Epistaxis / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D017211:Treatment Failure