title: Determinants of complications and outcome in high-risk squamous cell head-and-neck cancer treated with perioperative high-dose rate brachytherapy (PHDRB).
abstract: OBJECTIVE
  To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57).
  
  
  METHODS
  From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy.
  
  
  RESULTS
  Grade ≥4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade ≥3 and ≥4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV(150) values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035).
  
  
  CONCLUSIONS
  The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and exhaustive planning to reduce TV(150) values. Patients with high-risk margins, LVSI-positive status, and recurrent disease have a higher risk of treatment failure, and therefore risk-directed treatment strategies are required.
authors.affiliation: Department of Oncology, Clínica Universitaria de Navarra, Pamplona, Spain. rmartinezm@unav.es
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.forename: María
authors.initials: M
authors.lastname: Pagola Divassón
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.forename: Miren
authors.initials: M
authors.lastname: Gaztañaga
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno
authors.forename: Leire
authors.initials: L
authors.lastname: Arbea
authors.forename: Néstor
authors.initials: N
authors.lastname: Montesdeoca
authors.forename: Juan
authors.initials: J
authors.lastname: Alcalde
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D017211:Treatment Failure