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Title: Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes

Abstract

Purpose: To determine the optimal clinical target volume margins around the gross nodal tumor volume in head-and-neck cancer by assessing microscopic tumor extension beyond cervical lymph node capsules. Methods and Materials: Histologic sections of 96 dissected cervical lymph nodes with extracapsular extension (ECE) from 48 patients with head-and-neck squamous cell carcinoma were examined. The maximum linear distance from the external capsule border to the farthest extent of the tumor or tumoral reaction was measured. The trends of ECE as a function of the distance from the capsule and lymph node size were analyzed. Results: The median diameter of all lymph nodes was 11.0 mm (range: 3.0-30.0 mm). The mean and median ECE extent was 2.2 mm and 1.6 mm, respectively (range: 0.4-9.0 mm). The ECE was <5 mm from the capsule in 96% of the nodes. As the distance from the capsule increased, the probability of tumor extension declined. No significant difference between the extent of ECE and lymph node size was observed. Conclusion: For N1 nodes that are at high risk for ECE but not grossly infiltrating musculature, 1 cm clinical target volume margins around the nodal gross tumor volume are recommended to cover microscopic nodal extension in head-and-neckmore » cancer.« less

Authors:
 [1];  [2];  [2];  [3];  [3];  [3];  [3];  [3];  [3];  [4];  [5]
  1. Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
  2. Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
  3. Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
  4. Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
  5. Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States) and Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). E-mail: cchao@mdanderson.org
Publication Date:
OSTI Identifier:
20793331
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2005.08.020; PII: S0360-3016(05)02388-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; HAZARDS; HEAD; LYMPH NODES; METASTASES; NECK; PATIENTS

Citation Formats

Apisarnthanarax, Smith, Elliott, Danielle D., El-Naggar, Adel K., Asper, Joshua A. P.A., Blanco, Angel, Ang, K. Kian, Garden, Adam S., Morrison, William H., Rosenthal, David, Weber, Randal S., and Chao, K.S. Clifford. Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Apisarnthanarax, Smith, Elliott, Danielle D., El-Naggar, Adel K., Asper, Joshua A. P.A., Blanco, Angel, Ang, K. Kian, Garden, Adam S., Morrison, William H., Rosenthal, David, Weber, Randal S., & Chao, K.S. Clifford. Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes. United States. doi:10.1016/J.IJROBP.2005.0.
Apisarnthanarax, Smith, Elliott, Danielle D., El-Naggar, Adel K., Asper, Joshua A. P.A., Blanco, Angel, Ang, K. Kian, Garden, Adam S., Morrison, William H., Rosenthal, David, Weber, Randal S., and Chao, K.S. Clifford. Wed . "Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793331,
title = {Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes},
author = {Apisarnthanarax, Smith and Elliott, Danielle D. and El-Naggar, Adel K. and Asper, Joshua A. P.A. and Blanco, Angel and Ang, K. Kian and Garden, Adam S. and Morrison, William H. and Rosenthal, David and Weber, Randal S. and Chao, K.S. Clifford},
abstractNote = {Purpose: To determine the optimal clinical target volume margins around the gross nodal tumor volume in head-and-neck cancer by assessing microscopic tumor extension beyond cervical lymph node capsules. Methods and Materials: Histologic sections of 96 dissected cervical lymph nodes with extracapsular extension (ECE) from 48 patients with head-and-neck squamous cell carcinoma were examined. The maximum linear distance from the external capsule border to the farthest extent of the tumor or tumoral reaction was measured. The trends of ECE as a function of the distance from the capsule and lymph node size were analyzed. Results: The median diameter of all lymph nodes was 11.0 mm (range: 3.0-30.0 mm). The mean and median ECE extent was 2.2 mm and 1.6 mm, respectively (range: 0.4-9.0 mm). The ECE was <5 mm from the capsule in 96% of the nodes. As the distance from the capsule increased, the probability of tumor extension declined. No significant difference between the extent of ECE and lymph node size was observed. Conclusion: For N1 nodes that are at high risk for ECE but not grossly infiltrating musculature, 1 cm clinical target volume margins around the nodal gross tumor volume are recommended to cover microscopic nodal extension in head-and-neck cancer.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 64,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2006},
month = {Wed Mar 01 00:00:00 EST 2006}
}
  • Purpose: To determine the optimal clinical target volume (CTV) margins around the nodal gross tumor volume (GTV) in non-small-cell lung cancer (NSCLC) patients by assessing microscopic tumor extension beyond regional lymph node capsules. Methods and Materials: The incidence of nodal extracapsular extension (ECE) and relationship with nodal size were reviewed in 243 patients. Histologic sections of dissected regional lymph nodes up to 30 mm in size were examined to measure the extent of microscopic ECE. We determined the distribution of cases according to extent of ECE and the relationships between ECE extent and lymph node size, regional nodal disease extent,more » histologic type, and degree of differentiation. Results: The nodal ECE was seen in 41.6% of patients (101/243) and 33.4% of lymph nodes (214/640), and the incidence correlated to larger lymph node size positively. The extent of ECE was 0.7 mm in mean (range, 0-12.0 mm) and {<=}3 mm in 95% of the nodes. Positive correlations were found between extent of ECE and larger lymph node size ({>=}20 mm vs. 10-19 mm or <10 mm, p = 0.005), advanced nodal stage (N2 vs. N1, p = 0.046), and moderate or poor (vs. good or unknown) nodal differentiation (p = 0.002). ECE did not differ significantly by histologic type or nodal station. Conclusions: The incidence of ECE related to lymph node size, and ECE extent related to lymph node size, stage, and differentiation. It may be reasonable to recommend 3-mm CTV margins for pathologic lymph nodes <20 mm and more generous margins for lymph nodes {>=}20 mm.« less
  • Purpose: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed. Methods and Materials: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded. Results: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance =more » 2.4 mm [range: 0.05-7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance {>=}2 mm, 19% {>=}4 mm, and 6% {>=}6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA {>=}10 or biopsy Gleason score {>=}7, 21% had ECE {>=}2 mm and 5% {>=}4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE {>=}2 mm and 21% {>=}4 mm. Conclusions: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE >4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA {>=}10 ng/ml and biopsy Gleason score {>=}7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.« less
  • 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 231more » 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.« less
  • Purpose: Small lymph nodes (LN) show evidence of extracapsular extension (ECE) in a significant number of patients. This study was performed to determine the impact of ECE in LN {<=}7 mm as compared with ECE in larger LN. Methods and Materials: All tumor-positive LN of 74 head and neck squamous cell carcinoma (HNSCC) patients with at least one ECE positive LN were analyzed retrospectively for the LN diameter and the extent of ECE. Clinical endpoints were regional relapse-free survival, distant metastasis-free survival, and overall survival. The median follow-up for the surviving patients was 2.1 years (range, 0.3-9.2 years). Results: Forty-fourmore » of 74 patients (60%) had at least one ECE positive LN {<=}10 mm. These small ECE positive LN had a median diameter of 7 mm, which was used as a cutoff. Thirty patients (41%) had at least one ECE positive LN {<=}7 mm. In both univariate and multivariate Cox regression analyses, the incidence of at least one ECE positive LN {<=}7 mm was a statistically significant prognostic factor for decreased regional relapse-free survival (adjusted hazard ratio [HR]: 2.7, p = 0.03, 95% confidence interval [CI]: 1.1-6.4), distant metastasis-free survival (HR: 2.6, p = 0.04, 95% CI: 1.0-6.6), and overall survival (HR: 2.5, p = 0.03, 95% CI: 1.1-5.8). Conclusions: The incidence of small ECE positive LN metastases is a significant prognostic factor in HNSCC patients. Small ECE positive LN may represent more invasive tumor biology and could be used as prognostic markers.« less
  • Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initialmore » surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.« less