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Original Investigation |

Nodal Disease Burden for Early-Stage Oral Cancer ONLINE FIRST

Kelly Yi Ping Liu, MSc1,2; J. Scott Durham, MD3; Jonn Wu, MD4; Donald W. Anderson, MD3; Eitan Prisman, MD3; Catherine F. Poh, DDS, PhD1,2,5
[+] Author Affiliations
1Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada
2Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada
3Division of Otolaryngology–Head and Neck Surgery, Department of Oral Biological and Medical Science, University of British Columbia, Vancouver, Canada
4Department of Radiation Oncology, BC Cancer Agency, Vancouver Center, Vancouver, British Columbia, Canada
5Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
JAMA Otolaryngol Head Neck Surg. Published online August 25, 2016. doi:10.1001/jamaoto.2016.2241
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Importance  Nodal disease has a significant effect on survival of patients with oral squamous cell carcinoma (OSCC). The decision for elective neck dissection for clinically node-negative (cN0) disease remains elusive.

Objectives  To determine the efficacy of prophylactic neck treatment and to assess the value of commonly used clinicopathologic factors associated with nodal disease for early-stage OSCC.

Design, Setting, and Participants  This retrospective study from a population-based cancer registry included patients diagnosed as having OSCC from January 11, 2001, to December 24, 2007, who were identified from the British Columbia Cancer Agency Registry. Comprehensive clinicopathologic data, treatment information, and time to outcome were collected. Five-year overall survival, disease-specific survival, and cumulative incidence of regional failure (RF) were analyzed. Receiver operating characteristic curve analysis with sensitivity and specificity was used to determine the association of these covariates with RF during follow-up. Data were analyzed from January 16 to June 30, 2015.

Interventions  Follow-up of patients with cN0 OSCC with or without prophylactic neck treatment (elective neck dissection [END] and or radiotherapy).

Main Outcomes and Measures  Patient demographic characteristics, clinicopathologic data, treatment data, and time from the initial surgery to last follow-up, the development of RF, or death due to oral cancer or other causes.

Results  Of the 469 patients with cN0 primary OSCC who underwent intent-to-cure surgery for the intraoral lesion, 447 received local excision (LE) for the primary tumor (256 men [57.3%] and 191 women [42.7%]; mean [SD] age, 63.3 [14.7] years). Patients who received prophylactic treatment of the neck (n = 125) compared with LE only (n = 322) had no survival advantage. The estimated 5-year overall and disease-specific survival rates were 61.9% (95% CI, 56.5%-67.8%) and 80.8% (95% CI, 76.1%-85.6%), respectively, for the LE-only group; 54.4% (95% CI, 45.9%-64.5%) and 73.1% (95% CI, 65%-82.3%), respectively, for the LE + END ± radiotherapy group; and 61.7% (95% CI, 52.3%-72.8%) and 80.3% (95% CI, 72%-89.4%), respectively, for the LE + END group. Among the patients with cN0 disease receiving LE only, 89 (27.6%; 95% CI, 23%-33%) developed RF at a median time of 10.8 months, and 71 of the RFs (79.8%) developed within 30 months. Tumor depth of invasion of at least 4 mm and tumor grade of 2 or 3 showed an association with RF but had poor sensitivity and specificity.

Conclusions and Relevance  Commonly used pathologic factors to decide neck dissection for cN0 OSCC are not effective and can cause overtreatment or undertreatment. The need for identification of new objective approaches for risk assessment of RF is urgent.

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Figure 1.
Diagram of Study Patients

The diagram depicts by nodal status at initial presentation, initial treatment types, and nodal status at initial treatment and during follow-up. cN0 indicates clinically node-negative disease; cN+, clinically node-positive disease; END, elective neck dissection; LE, local excision; OSCC, oral squamous cell carcinoma; pN0, pathologically proven node-negative disease at surgery; pN+, pathologically proven node-positive disease at surgery or during follow-up; RF, regional failure (development of pN+ in patients with cN0 disease at follow-up); and RT, radiotherapy. Dashed line indicates clinical follow-up after initial treatment.

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Figure 2.
Kaplan-Meier Analysis of 5-year Overall (OS) and Disease-Specific (DSS) Survival

Includes patients with clinically node-negative (cN0) disease at presentation. END indicates elective neck dissection; LE, local excision; and RT, radiotherapy. Differences in survival time between groups were tested by log-rank test, with P < .05 considered as significant.

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Figure 3.
Disease-Specific Survival (DSS) and Cumulative Incidence of Regional Failure (RF)

Includes 322 patients with clinically node-negative (cN0) disease who received local excision without prophylactic neck treatment. Outcomes (denoted →) include continued cN0 disease and pathologically proven node-positive disease (pN+). Dashed line indicates 95% CI.

aIndicates log-rank test of difference at 2, 3, and 5 years of P < .001.

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Figure 4.
Overtreatment or Undertreatment of Patients by Depth of Invasion of Tumor (DOI)

Includes patients with clinically node-negative disease (cN0). Outcomes (denoted →) include continued cN0 disease and pathologically proven node-positive disease (pN+). Overtreatment is calculated as the total number of the cN0→cN0 group at and above the corresponding cutoff divided by the total number of treated patients at and above the corresponding DOI; undertreatment, the total number of the cN0→pN+ group below the corresponding cutoff divided by the total number of patients below the corresponding DOI.

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