title: Distant Metastases Following Postoperative Intensity-Modulated Radiotherapy for Oral Cavity Squamous Cell Carcinoma.
abstract: Advances in surgical techniques, the advent of intensity-modulated radiotherapy (IMRT), and the use of concurrent chemotherapy in oral squamous cell carcinoma (OSCC) have led to improvement of locoregional control (LRC), but not distant control (DC). Moreover, the development of distant metastases (DM) in OSCC has a dismal prognosis.
  
  
  
  To determine the characteristics and risk factors of DM following postoperative IMRT in OSCC, and to identify the clinicopathological features that could be associated with distant-only failure (DOF).
  
  
  
  Retrospective study of 300 OSCC patients (192 [64%] men and 108 [36%] women) treated with surgery and postoperative IMRT between 2005-2012 in a tertiary cancer center.
  
  
  
  All patients underwent initial primary curative-intent resection with postoperative IMRT with or without concurrent chemotherapy based on predefined risk features.
  
  
  
  Locoregional control, DC, overall survival (OS), and Radiation Therapy Oncology Group grade of 3 or higher late toxic effects. Multivariable analysis identified predictors for DM.
  
  
  
  Overall 300 patients were identified (histological grade 2-3 [G2-3], 285 [95%]; pT3-4, 121 [41%]; pN2-3, 141 [47%]). Positive resection margin was present in 64 of 300 (21%) patients and extracapsular extension in 89 of 281 (32%) neck dissections. Median IMRT dose was 66 Gy and concurrent chemotherapy was used in 73 patients (24%). Median follow-up was 41 months. The 5-year local, regional, and distant control and OS were 85%, 82%, 86%, and 69%, respectively. On multivariable analysis, pN2-3 (hazards ratio, 5.7; 95% CI, 2.2-14.7) and G2-3 (HR, 4.9; 95% CI, 2.8-8.9) were predictive of DM. Thirty-nine patients developed DM, of which 20 (51%) were DOF and 12 (31%) were oligometastatic (≤5 lesions). The clinicopathological characteristics in DOF were similar to patients with DM subsequent to locoregional failure. In patients with G2-3, pN2-3, and extracapsullar extension (all together), the 5-year cumulative incidence of DOF was 22%.
  
  
  
  Surgery and postoperative IMRT with or without concurrent chemotherapy achieved encouraging outcomes. The clinicopathological characteristics of DOF and DM with locoregional failure were similar. Patients with G2-3, pN2-3, and extracapsullar extension (all together) have higher risk of DOF. Both pN2-3 and G2-3 were independent predictors of DM. Patients with these risk factors may be candidates for prospective clinical trials of intensified therapy or surveillance strategies.
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Hosni
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shao Hui
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Princess Margaret Cancer Centre, Department of Biostatistics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Princess Margaret Cancer Centre, Department of Biostatistics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Bratman
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Meredith
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Waldron
authors.affiliation: Princess Margaret Cancer Centre, Department of Medical Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Spreafico
authors.affiliation: Princess Margaret Cancer Centre, Department of Otolaryngology-Head & Neck Surgery/Surgical Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: De Almeidad
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Princess Margaret Cancer Centre, Department of Otolaryngology-Head & Neck Surgery/Surgical Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000556:secondary* / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology* / Q000628:therapy*; D037981:Neck Dissection; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin