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Original Investigation
December 29, 2016

Distant Metastases Following Postoperative Intensity-Modulated Radiotherapy for Oral Cavity Squamous Cell Carcinoma

Author Affiliations
  • 1Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
  • 2Princess Margaret Cancer Centre, Department of Biostatistics, University of Toronto, Toronto, Ontario, Canada
  • 3Princess Margaret Cancer Centre, Department of Medical Oncology, University of Toronto, Toronto, Ontario, Canada
  • 4Princess Margaret Cancer Centre, Department of Otolaryngology—Head & Neck Surgery/Surgical Oncology, University of Toronto, Toronto, Ontario, Canada
JAMA Otolaryngol Head Neck Surg. Published online December 29, 2016. doi:10.1001/jamaoto.2016.3668
Key Points

Question  What are the characteristics and risk factors of distant metastases (DM) in oral squamous cell carcinoma following postoperative intensity-modulated radiotherapy?

Findings  In this retrospective study, with prospectively acquired data, the clinicopathological characteristics of distant-only failure and DM with locoregional failure were similar. Both pN2-3 and G2-3 were independent predictors of DM.

Meaning  Our results can help in the identification of a subset of high-risk patients characterized by poor clinical outcomes owing to high metastatic potential with a short latency of metastatic disease. These factors could also be employed for trials of treatment intensification or screening strategies for DM in the early years after surgery.

Abstract

Importance  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.

Objective  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).

Design, Setting, and Participants  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.

Interventions  All patients underwent initial primary curative-intent resection with postoperative IMRT with or without concurrent chemotherapy based on predefined risk features.

Main Outcomes and Measures  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.

Results  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%.

Conclusions and Relevance  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.

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