Initially-positive margins predict worse survival in primary, but not salvage, total laryngectomy

Presentation: C048
Topic: Pharynx / Larynx Cancer
Type: Poster
Date: Thursday, April 19, 2018
Session: 9:00 AM - 7:00 PM
Authors: Patrick Tassone, MD, Corey Savard, Michael Topf, MD, William Keane, MD, Adam Luginbuhl, MD, Joseph Curry, MD, David Cognetti, MD
Institution(s): Thomas Jefferson University

Importance: Frozen section analysis of margins is routinely performed during total laryngectomy (TL) for squamous cell carcinoma (SCCa); in the case of initially positive frozen margins, re-resection to negative margins can often be accomplished. Some evidence suggests that initially-positive margins predict worse survival in head and neck cancer even when final margins are negative, but the significance of initially-positive frozen margins in TL is poorly understood.

Objectives: To determine the impact on disease-free survival of initially-positive frozen margins among patients treated with TL for SCCa with negative final margins.

Design: Retrospective cohort study.

Setting: Tertiary care center.

Participants: The records of 225 consecutive patients treated with TL for SCCa were reviewed for demographics, staging, pathologic markers, and outcomes. Patients were excluded if they had positive final margins after TL.

Intervention: All patients were treated with TL for SCCa.

Main outcomes: Potential predictors of disease-free survival (DFS) were analyzed using a univariate and multivariate cox proportional hazard model. Separate analyses were conducted for all TL patients, primary TL patients, and salvage TL patients.

Results: Among all 225 TL patients, 127 patients had primary TL and 98 had salvage TL, with average follow-up time of 29.3 months. Frozen margins were initially positive in 42 (19%) patients; initially positive margins occurred in 23 (18%) primary TL patients and 19 (19%) salvage patients. On multivariate analysis of all 225 patients, salvage laryngectomy was predictive of significantly worse DFS (HR 3.35, 95%CI 1.76-6.36, p<0.001) and extracapsular nodal extension (ECE) approached significance (HR 2.2, 95% CI 0.99-4.88, p=0.053).

Among 98 salvage TL patients, positive lymph nodes (HR 2.69, 95% CI 1.41-5.11, p=0.003), lymphovascular invasion (HR 2.01, 95% CI 1.03-3.94, p=0.041), ECE (HR 3.94, 95% CI 1.83-8.49, p=0.005), and adjuvant therapy (HR 2.44, 95% CI 1.25-4.78, p=0.009) were predictive of worse DFS on univariate analysis, but no factors remained significant on multivariate analysis, including initially-positive margins (HR 1.05, 95% CI 0.38-2.35, p=0.93).

Among 127 primary TL patients, positive lymph nodes (HR 2.95, 95% CI 1.28-6.81, p=0.011), lymphovascular invasion (HR 2.94, 95% CI 1.37-6.31, p=0.006), ECE (HR 3.46, 1.67-7.16, p<0.001), and initially-positive margins (HR 3.11, 95% CI 1.39-6.96, p=0.006) were predictive of worse DFS; however, only initially-positive margins predicted significantly worse DFS on multivariate analysis of primary TL patients (HR 5.01, 95% CI 1.55-16.2, p=0.007).

Conclusions and Relevance: In this series, patients undergoing salvage TL had worse DFS than patients undergoing primary TL. Initially-positive margins predicted worse DFS among primary TL patients despite negative microscopic margins on final pathology. This effect was independent of adjuvant treatment, and may indicate aggressive tumor behavior in the setting of primary laryngeal squamous cell carcinoma.