Positive Postradiotherapy Planned Neck Dissection is Strongly Associated with Increased Distant Metastasis Rather Than Regional Relapse

Abstract

Purpose/Objective(s)To evaluate the clinicopathological predictors for planned neck dissection (PND) positivity and outcome following definitive radiotherapy (RT) ± concurrent chemotherapy (CRT) in head and neck cancer (HNC) patients.Materials/MethodsA retrospective review was conducted of all newly diagnosed patients with squamous cell carcinomas of oropharynx, hypopharynx, larynx, and unknown primary that underwent a PND following RT/CRT between 1998 and 2007. PND was defined as neck dissection (ND) performed within 15 weeks after RT/CRT without clinical evidence of persistent primary disease. All positive (PND+) specimens were confirmed by pathology review. Univariate and multivariate analyses were performed for predictors of PND positivity and outcomes including 5-year overall survival (OS), cause specific survival (CSS), disease-free survival (DFS), local control (LC), regional control (RC) and distant metastasis rate (DM). In the PND+ cohort, we further investigated the predictive value of positive nodal resection margin (Margin+), level 4/5 nodal involvement (LN4/5+), extracapsular extension/soft-tissue deposit (ECE/STD) and lympho-vascular involvement (LVI) in the neck specimen for OS, CSS, and DFS. All time-to-event outcomes were calculated from the date of PND.ResultsA total of 194 PNDs (50 PND+ and 144 PND-) were performed in 1930 consecutive HNC patients. Median follow-up was 4.8 (0.2 - 10.7) years. Primary tumor sites were 139 (72%) oropharynx, 19 (10%) hypopharynx, 10 (5%) larynx, and 26 (13%) unknown primary. The initial N status was 9 (5%) N1, 150 (77%) N2 and 35 (18%) N3. On univariate analysis, older age, hypopharynx primary site, T3-4, and N2c-N3 were all predictors for PND+ (all p < 0.05); however, only older age [hazard ratio (HR) 1.05, p = 0.01] and hypopharynx primary site (HR 4.39, p = 0.01) remained significant on multivariate analysis. In comparison to PND- patients, the PND+ cohort had diminished OS (33% vs. 77%), DFS (32% vs. 77%), and CSS (50% vs. 87%) (all p < 0.01). The PND+ cohort had much higher DM (44% vs. 11%, p < 0.01) with moderately reduced LC (86% vs. 96%, p < 0.01) and similar RC (94% vs. 99%, p = 0.07). In the PND+ cohort, Margin+, LN4/5+, ECE/STD, and LVI were all adverse predictors for OS, DFS and CSS on univariate analysis (all p < 0.05). However, on multivariate analysis only the presence of ECE/STD and LVI remained as significant predictors for OS, DFS, and only ECE/STD for CSS.ConclusionsOlder age and hypopharynx primary site were associated more frequently than other factors examined with positive post-radiotherapy PND. PND+ was associated with diminished survival, mainly attributed to significantly increased DM rather than reduced LC and RC. The presence of ECE/STD and LVI was associated with reduced survival for PND+ patients. Purpose/Objective(s)To evaluate the clinicopathological predictors for planned neck dissection (PND) positivity and outcome following definitive radiotherapy (RT) ± concurrent chemotherapy (CRT) in head and neck cancer (HNC) patients. To evaluate the clinicopathological predictors for planned neck dissection (PND) positivity and outcome following definitive radiotherapy (RT) ± concurrent chemotherapy (CRT) in head and neck cancer (HNC) patients. Materials/MethodsA retrospective review was conducted of all newly diagnosed patients with squamous cell carcinomas of oropharynx, hypopharynx, larynx, and unknown primary that underwent a PND following RT/CRT between 1998 and 2007. PND was defined as neck dissection (ND) performed within 15 weeks after RT/CRT without clinical evidence of persistent primary disease. All positive (PND+) specimens were confirmed by pathology review. Univariate and multivariate analyses were performed for predictors of PND positivity and outcomes including 5-year overall survival (OS), cause specific survival (CSS), disease-free survival (DFS), local control (LC), regional control (RC) and distant metastasis rate (DM). In the PND+ cohort, we further investigated the predictive value of positive nodal resection margin (Margin+), level 4/5 nodal involvement (LN4/5+), extracapsular extension/soft-tissue deposit (ECE/STD) and lympho-vascular involvement (LVI) in the neck specimen for OS, CSS, and DFS. All time-to-event outcomes were calculated from the date of PND. A retrospective review was conducted of all newly diagnosed patients with squamous cell carcinomas of oropharynx, hypopharynx, larynx, and unknown primary that underwent a PND following RT/CRT between 1998 and 2007. PND was defined as neck dissection (ND) performed within 15 weeks after RT/CRT without clinical evidence of persistent primary disease. All positive (PND+) specimens were confirmed by pathology review. Univariate and multivariate analyses were performed for predictors of PND positivity and outcomes including 5-year overall survival (OS), cause specific survival (CSS), disease-free survival (DFS), local control (LC), regional control (RC) and distant metastasis rate (DM). In the PND+ cohort, we further investigated the predictive value of positive nodal resection margin (Margin+), level 4/5 nodal involvement (LN4/5+), extracapsular extension/soft-tissue deposit (ECE/STD) and lympho-vascular involvement (LVI) in the neck specimen for OS, CSS, and DFS. All time-to-event outcomes were calculated from the date of PND. ResultsA total of 194 PNDs (50 PND+ and 144 PND-) were performed in 1930 consecutive HNC patients. Median follow-up was 4.8 (0.2 - 10.7) years. Primary tumor sites were 139 (72%) oropharynx, 19 (10%) hypopharynx, 10 (5%) larynx, and 26 (13%) unknown primary. The initial N status was 9 (5%) N1, 150 (77%) N2 and 35 (18%) N3. On univariate analysis, older age, hypopharynx primary site, T3-4, and N2c-N3 were all predictors for PND+ (all p < 0.05); however, only older age [hazard ratio (HR) 1.05, p = 0.01] and hypopharynx primary site (HR 4.39, p = 0.01) remained significant on multivariate analysis. In comparison to PND- patients, the PND+ cohort had diminished OS (33% vs. 77%), DFS (32% vs. 77%), and CSS (50% vs. 87%) (all p < 0.01). The PND+ cohort had much higher DM (44% vs. 11%, p < 0.01) with moderately reduced LC (86% vs. 96%, p < 0.01) and similar RC (94% vs. 99%, p = 0.07). In the PND+ cohort, Margin+, LN4/5+, ECE/STD, and LVI were all adverse predictors for OS, DFS and CSS on univariate analysis (all p < 0.05). However, on multivariate analysis only the presence of ECE/STD and LVI remained as significant predictors for OS, DFS, and only ECE/STD for CSS. A total of 194 PNDs (50 PND+ and 144 PND-) were performed in 1930 consecutive HNC patients. Median follow-up was 4.8 (0.2 - 10.7) years. Primary tumor sites were 139 (72%) oropharynx, 19 (10%) hypopharynx, 10 (5%) larynx, and 26 (13%) unknown primary. The initial N status was 9 (5%) N1, 150 (77%) N2 and 35 (18%) N3. On univariate analysis, older age, hypopharynx primary site, T3-4, and N2c-N3 were all predictors for PND+ (all p < 0.05); however, only older age [hazard ratio (HR) 1.05, p = 0.01] and hypopharynx primary site (HR 4.39, p = 0.01) remained significant on multivariate analysis. In comparison to PND- patients, the PND+ cohort had diminished OS (33% vs. 77%), DFS (32% vs. 77%), and CSS (50% vs. 87%) (all p < 0.01). The PND+ cohort had much higher DM (44% vs. 11%, p < 0.01) with moderately reduced LC (86% vs. 96%, p < 0.01) and similar RC (94% vs. 99%, p = 0.07). In the PND+ cohort, Margin+, LN4/5+, ECE/STD, and LVI were all adverse predictors for OS, DFS and CSS on univariate analysis (all p < 0.05). However, on multivariate analysis only the presence of ECE/STD and LVI remained as significant predictors for OS, DFS, and only ECE/STD for CSS. ConclusionsOlder age and hypopharynx primary site were associated more frequently than other factors examined with positive post-radiotherapy PND. PND+ was associated with diminished survival, mainly attributed to significantly increased DM rather than reduced LC and RC. The presence of ECE/STD and LVI was associated with reduced survival for PND+ patients. Older age and hypopharynx primary site were associated more frequently than other factors examined with positive post-radiotherapy PND. PND+ was associated with diminished survival, mainly attributed to significantly increased DM rather than reduced LC and RC. The presence of ECE/STD and LVI was associated with reduced survival for PND+ patients.