The clinical significance of tumor lymphangiogenesis continues to be an area of active research. We hypothesize that high peritumoral and intratumoral lymphatic vessel density (LVD) predict for inferior oncologic outcomes, including local failure (LF), progression-free survival (PFS), and overall survival (OS).
Newton J. Hurst, Jr., MD, PhD, Michael Dominello, DO, Gregory Dyson, PhD, Hayan Jaratli, MD, Meenu Sharma, MD, Yasim Ahmed, MD, Antoine Melkane, MD, Christopher Rose, MD, John Jacobs, MD, Tamar Giorgadze, MD, PhD, Harold Kim, MD; Wayne State University; Detroit Medical Center
Purpose and Objectives: The clinical significance of tumor lymphangiogenesis continues to be an area of active research. We hypothesize that high peritumoral and intratumoral lymphatic vessel density (LVD) predict for inferior oncologic outcomes, including local failure (LF), progression-free survival (PFS), and overall survival (OS).
Materials and Methods: Selected blocks from formalin-fixed, paraffin-embedded laryngectomy specimens were sectioned and stained with hematoxylin-eosin and immunostained with D2-40, a specific lymphatic endothelial cell marker. Peritumoral and intratumoral LVD was determined in tumor vessel “hot spots” using light microscopy (20× magnification) by four observers. The mean vessel counts in three “hot spots” per section were recorded. All surgical specimens were from patients with T3/T4 laryngeal or T4 hypopharyngeal cancer treated at our institution from 1999 through 2010. Charts were retrospectively reviewed for demographic, patient characteristic, and oncologic outcome data. All patients had undergone laryngectomy followed by concurrent chemoradiotherapy. Radiation therapy (RT) was delivered using a 3-field or intensity-modulated RT (IMRT) technique to a prescribed dose of 60–66 Gy. Chemotherapy was generally platinum-based, with patients receiving up to three cycles. LF was fitted with a competing risks model, with death as the competing risk. PFS and OS were calculated with Cox regression. Recursive partitioning analysis (RPA) was used to identify thresholds for peritumoral LVD and intratumoral LVD for association with PFS.
Results: A total of 43 patients who underwent laryngectomy followed by 1) concurrent chemoradiotherapy (40 patients) or 2) radiotherapy alone (3 patients) and whose tissues were evaluable for staining at our institution were included in the present analysis. Median age of this cohort was 56.8 years, with 11 females (25.6%) and 32 males (74.4%). Nineteen patients had T3 disease (44.2%), while 24 (55.8%) had T4 disease. Fourteen had N0, 5 had N1, 21 had N2, and 3 had N3 disease. Twelve-month OS, PFS, and LF for the cohort were 8 months (95% confidence interval [CI], 6.6–9.8), 7.1 months (95% CI, 5.5–9.0), and 1.1 months (95% CI, 0.36–2.3), respectively. Patients identified as having peritumoral LVD > 0 demonstrated a better median PFS (3.04 years; 95% CI, 1.05–5.35) than those with 0 peritumoral LVD (0.80 years; 95% CI, 0.48–NR; P = .03). When we evaluated those patients with intratumoral LVD with RPA, no statistical significance was reached for PFS (P = .24).
Conclusions: Patients with locally advanced laryngeal/hypopharyngeal cancer treated with laryngectomy and concurrent chemoradiotherapy who have any staining for peritumoral lymphatics have a statistically significantly better PFS than patients in whom the specimen shows no staining for peritumoral lymphatics. Our findings do not support our hypothesis and may reflect the advanced nature of disease in the patient population examined. Further study in this area examining earlier-stage patients is under way to further characterize the potential utility of this staining technique.