Clinical Investigation
Quantitative Analysis of Extracapsular Extension of Metastatic Lymph Nodes and its Significance in Radiotherapy Planning in Head and Neck Squamous Cell Carcinoma

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Purpose

We performed a histopathologic analysis to assess the extent of the extracapsular extension (ECE) beyond the capsule of metastatic lymph nodes (LN) in head and neck cancer to determine appropriate clinical target volume (CTV) expansions.

Methods and Materials

All tumor-positive LN of 98 patients who underwent a neck dissection with evidence of ECE in at least one LN were analyzed by a single pathologist. The largest diameters of all LN, and in the case of ECE, the maximal linear distance, from the capsule to the farthest extent of tumor or tumoral reaction were recorded.

Results

A total of 231 LN with ECE and 200 tumor-positive LN without ECE were analyzed. The incidence of ECE was associated with larger LN size (p < 0.001). Of all tumor-positive LN with a diameter of < 10 mm or < 5 mm, 105/220 (48%) nodes or 17/59 (29%) nodes, respectively, showed evidence of ECE. The mean and median extent values of ECE were 2 and 1 mm (range, 1–10 mm) and the ECE was ≤ 5 mm in 97% and ≤ 3 mm in 91% of the LN, respectively. Overall, the extent of ECE was significantly correlated with larger LN size (Spearman's correlation coefficient = 0.21; p = 0.001).

Conclusions

The incidence of ECE is associated with larger LN size. However, ECE is found in a substantial number of LN with a diameter of < 10 mm. The use of 10-mm CTV margins around the gross tumor volume seems appropriate to account for ECE in radiotherapy planning of head and neck cancer.

Introduction

Achieved by significant technological advances during the last 2 decades, intensity-modulated radiation therapy became the gold standard treatment in radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC). Its increased target coverage along with better sparing of the normal organs at risk (OAR) has led to promising treatment outcomes 1, 2, 3. RT planning, especially the delineation of the clinical target volume (CTV), is crucial in this respect and was therefore intensively addressed in the literature 4, 5, 6, 7. Protection of the OAR without compromising the tumor target coverage is possible only with extensive knowledge about the extension and spread of the tumor. Extracapsular extension (ECE) of tumor cells beyond the capsule of the lymph nodes (LN) is a well-known adverse prognostic factor on recurrence and survival in HNSCC 8, 9, 10, 11, 12, 13, 14, 15, 16. However, there is a lack of evidence concerning the size of safety margins warranted to account for the risk of ECE in CTV delineation, and the margins used at various institutions range from 5 mm to 20 mm. The true extent of microscopic ECE in metastatic LN of HNSCC was recently described (17) and, as a conclusion, 10-mm CTV margins for N1 or <30 mm N2b or N2c LN without gross infiltration of the musculature were generally recommended. In this histopathologic study, we analyzed the diameter of all tumor-positive LN and the incidence and extent of ECE and infiltration of the musculature in a large cohort of HNSCC patients to reveal more insight into the true extension of ECE to enhance future CTV delineation in HNSCC.

Section snippets

Patient selection and ECE measurement

A search of the institutional database of the Department of Pathology, University of Bern, was performed for patients with HNSCC who had documented evidence of ECE in at least one LN after they underwent a neck dissection in the Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, between January 1990 and July 2007. Patients who had received preoperative RT or chemotherapy or those in whom the LN with ECE were in a recurrence

Patient characteristics

Patient characteristics are summarized in Table 1. Patients were staged according to the American Joint Committee on Cancer 2002 guidelines (18). Sixty-eight (69%) of the patients underwent an operation of the primary tumor; thus, the pathological tumor category was available, while for the remaining patients, the tumor category was assessed clinically.

A mean and median of 6 and 5, respectively, LN specimens were found to be tumor positive (range, 1–20 specimens), and a mean and median of 2 LN

Discussion

This study accounts for the generally low level of evidence in CTV delineation for LN at risk for ECE in RT of HNSCC and recommends the use of 10-mm CTV margins around the gross tumor volume (GTV), based on histopathologic analysis. Apisarnthanarax et al. were the first to describe the true extension of the ECE in 96 nodes of 48 patients, which was <5 mm in 96% of the nodes; however, they failed to demonstrate a correlation between the extent of ECE and LN size. Unfortunately, neither the

Conclusions

The incidence and extension of ECE are associated with larger LN size. We recommend the use of 10-mm CTV margins around the GTV to account for ECE in patients with N1 or <30 mm N2b or N2c HNSCC.

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