Planned Neck Dissection Research Articles

Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers

BackgroundThe purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer.MethodsWe retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60-70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy.ResultsNeck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post-radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC.ConclusionsThe neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy.

Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

This analysis was undertaken to assess the need for planned neck dissection in patients with a complete response (CR) of involved nodes after irradiation and to determine the benefit of a neck dissection in those with less than CR by tumor site. Our cohort included 880 patients with T1-4, N1-3M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received treatment between 1994 and 2004. Survival curves were calculated by the Kaplan-Meier Method, comparisons of rates with the log-rank test and prognostic factors by Cox's proportional hazard model. Nodal CR occurred in 377 (43%) patients, of whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with CR was 92%. Two hundred sixty-eight of the remaining patients (53%) underwent neck dissections. The 5-year actuarial regional control rate for patients without a CR was 84%. Those who had a neck dissection fared better with 5-year actuarial regional control rates of 90% and 76% for those operated and those not operated (p < 0.001). Variables associated with poorer regional control rates included higher T and N stage, non-oropharynx cancers, non-CR, both clinical and pathological. With 92% 5-year neck control rate without neck dissection after CR, there is little justification for systematic neck dissection. The addition of a neck dissection resulted in higher neck control after partial response though patients with viable tumor on pathology specimens had poorer outcomes. The identification of that subgroup that benefits from additional treatment remains a challenge.

Planned Neck Dissection Following Radiation Treatment for Head and Neck Malignancy

Introduction. Optimal therapy for patients with metastatic neck disease remains controversial. Neck dissection following radiotherapy has traditionally been used to improve locoregional control. Methods. A retrospective review of 28 patients with node-positive head and neck malignancy treated with planned neck dissection following radiotherapy between January 2002 and December 2005 was performed to assess treatment outcomes. Results. Median interval to neck dissection was 9.6 weeks with a median number of 21 + 9 lymph nodes per specimen. Ten of 31 (32%) neck dissection specimens demonstrated evidence of residual carcinoma. Overall survival at two years was 85%; five-year overall survival was 65%. Concurrent chemotherapy did not impact the presence of residual neck disease. Conclusion. Based on the frequency of residual malignancy in the neck of patients treated with primary radiotherapy, a planned, postradiotherapy neck dissection should be strongly advocated for all patients with advanced-stage neck disease.

Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients

Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h) daily for five days and 5-fluorouracil (600 mg/m2/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events.

A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

Patterns of failure and histopathologic outcome predictors following definitive radiotherapy and planned neck dissection with residual disease

Our aim was to report patterns of failure and histopathological predictors in patients with head and neck cancer treated by planned neck dissection. We reviewed all new patients with head and neck cancer who underwent a planned neck dissection in our institution from 1998 to 2007. Patterns of failure after positive planned neck dissection were reported. The frequency and predictive value of histopathologic features were analyzed. Fifty positive planned neck dissection and 144 negative planned neck dissection cases were identified. The positive planned neck dissection cohort had lower 5-year overall survival (OS; 33% vs 77%; p < .01), a significantly higher distant metastasis (DM; 44% vs 11%; p < .01), a moderately lower local (86% vs 96%; p < .01), and a similar regional control (94% vs 99%; p = .07) compared to the negative planned neck dissection cohort. Extracapsular extension/carcinoma within soft tissue and lymphovascular invasion were adverse survival predictors for patients with positive planned neck dissection on univariate and multivariate analysis. Positive planned neck dissection is associated with lower survival, predominantly attributed to significantly increased DM rather than reduced locoregional control.

Residual Lymph Node Metastasis in Planned Neck Dissection

Objective: Clarify the effectiveness of planned neck dissection (PND) after concurrent chemoradiotherapy (CCRT), we investigated residual lymph node metastasis; imaging tests such as positron emission tomography (PET), computed tomography (CT), and ultrasonography at pre- and post-CCRT; and the adverse effects of PND. Method: CCRT combined with PND was performed on 13 patients with oropharyngeal carcinoma, 4 with hypopharyngeal carcinoma, and 2 with laryngeal carcinoma. All primary lesions showed complete response to CCRT. Histopathologic examination of neck specimens and imaging tests were employed to evaluate the effect of CCRT. Results: Eight of 19 patients (47%) had viable carcinoma in their lymph nodes. Patients with poorly differentiated carcinoma in the primary lesion tended to have residual lymph nodes. Most of the residual neck specimens belonged to the level III or level IV lymph node group. Major complications of PND were prolonged laryngeal edema, dysphasia, and disturbance of shoulder movement. Tracheotomies were performed in 42% of all cases. Positive and negative predictive values of PET examination before PND were 50% and 73%, respectively. None of the patients with PND experienced local or lymph node recurrence. Conclusion: Residual lymph nodes were frequently observed in head and neck carcinomas. Of the imaging tests, PET was sufficient for detecting residual regions. Although PND is a useful tool, related complications were frequently observed. A more accurate detection system is needed to reduce unnecessary neck dissections.

Oropharyngeal Cancer with Neck Complete Response

Objective: Evaluate the necessity of planned neck dissection in patients with oropharyngeal cancer by analyzing N2, N3 with complete response after primary treatment. Method: A retrospective chart review of 327 patients with oropharynx squamous cell carcinoma over a 24-year period was conducted. Overall survival rate was analyzed using the Kaplan-Meier method. Results: Among the 64 patients, all the recurrent cases had T staging more than 3, and N staging more than N2b without any evidence of metastasis except 1 case. Recurrence varied from 3 to 43 months. Disease recurrence was reported in 8 cases which include 3 primary recurrences, 2 neck recurrences, and 3 both primary and neck recurrences. Distant metastasis was reported in 2 cases. Survival according to initial treatment modality didn’t show any statistical significance. Overall 5 year survival rate reached 80% using the Kaplan-Meier method. Conclusion: Neck metastasis in oropharyngeal squamous cell carcinoma is well treated with chemotherapy and radiotherapy resulting in low neck recurrence and high 5-year survival rate. Patients with oropharyngeal cancer with complete cervical response can be safely observed without planned neck dissection.

Management of the Neck in HNSCC: Controversies and Guidelines in 2011

Program Description: Neck dissection continues to be an integral part of surgical treatment of head and neck squamous cell carcinoma (HNSCC). The operation has evolved significantly since first described by Crile and others more than 100 years ago. With the development of more precise imaging modalities, chemoradiation treatment protocols, and transoral laser (TLM) and robotic (TORS) surgery, it is important to reexamine guidelines for management of the neck. This miniseminar will focus on several relevant topics pertaining to treatment of the neck in HNSCC: 1) The role of imaging in planning treatment of the neck will be discussed. Pre-treatment imaging with PET, CT, and MRI can yield valuable information regarding subclinical neck metastases and may help in treatment planning, particularly for T1 and T2 primary tumors. The timing and optimal modality for post-chemoradiation imaging remains controversial. 2) The advantages and disadvantages for upfront neck dissection for small and unknown primary HNSCC will be addressed. Elective neck dissection vs radiation vs observation for clinically negative necks will be discussed. 3) Management of the neck in conjunction with TLM/TORS will be examined. With increasing use of TLM/TORS for surgical management of HNSCC, it is essential that the neck is treated appropriately. Guidelines for neck dissection in conjunction with TLM/TORS will be outlined. 4) Paradigms for management of the neck following chemoradiation continue to evolve. Chemoradiation protocols for HNSCC are effective in eradicating advanced nodal disease as well as the primary tumor. Thus, the use of planned neck dissection for N2 and N3 disease following completion of chemoradiation is giving way to the use of salvage neck dissection. Also, concepts have changed toward the use of more limited neck dissections. Finally, challenging cases involving management of neck disease will be presented to the panel of experts, for discussion and audience participation. Educational Objectives: 1) Understand the role of imaging in planning treatment of the neck. 2) Understand how to manage the neck in conjunction with TLM/TORS. 3) Understand how paradigms for management of the neck following chemoradiation have evolved.

Concurrent chemoradiotherapy and brachytherapy boost for base of tongue cancer treatment outcomes.

e16026 Background: Concurrent chemo-radiotherapy (CCRT) and brachytherapy boost (BT) for base of tongue (BOT) cancers have been associated with high rates of organ preservation, swallowing function and better therapeutic ratio. We report our experience of long term outcomes for BOT patients (pts) treated with reduced dose CCRT with BT. Methods: Single institute retrospective study of 89 BOT cancer pts with characteristics as follows: median age 57 (41-82yr) Male: 89% and staged as follows: II 11%, III 10%, IVA/B 79%; T1:8%, T2:45%, T3: 30%, T4: 17%, N2/3 80%. Pts were treated initially with external beam radiation therapy (EBRT) to a median dose of 60Gy (45-72Gy) followed by a base of tongue brachytherapy boost [median dose 18Gy (9-30Gy)]. Concurrent chemotherapy or biologic therapy was given in 81% (mostly given as single agent Cisplatin and to lesser extent, Carboplatin, Erbitux, taxanes or combined). Planned neck dissection performed in 79%. EBRT was delivered with a 2D technique in 61% and IMRT in 39%...

Transoral robotic‐assisted microvascular reconstruction of the oropharynx

Transoral robotic‐assisted microvascular reconstruction of the oropharynx

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma1

To report the outcomes after intensity-modulated radiotherapy (IMRT) for patients with oropharyngeal squamous cell carcinoma. Retrospective review. Between July 2001 and March 2007, a total of 130 patients were treated with definitive IMRT for squamous cell carcinoma of the oropharynx. Forty-seven patients (36%) had T3 (26 patients) or T4 (21 patients) cancers and 117 patients (90%) had overall stage III to IV disease. The fractionation schedules employed included the following: once daily, 12 patients (9%); hyperfractionation, three patients (2%); and concomitant boost, 115 patients (89%). Seventy-nine patients (61%) received adjuvant chemotherapy, and 54 patients (42%) underwent a planned neck dissection. Median follow-up was 3.5 years, (range, 0.2-7.7 years). Median follow-up for surviving patients was 3.8 years (range, 2.1-7.7 years). The 5-year local control rates were as follows: T1, 93%; T2, 91%; T3, 82%; T4, 67%; and overall, 87%. The 5-year local-regional control rates were as follows: stage I to II, 92%; stage III, 72%; stage IVA, 94%; stage IVB, 71%; and overall, 84%. The 5-year distant metastasis-free survival rate was 93%. The 5-year cause-specific and overall survival rates were 85% and 76%, respectively. Severe late complications occurred in 11 patients (8%). In our experience, IMRT resulted in local-regional control rates that are comparable to those achieved with more conventional techniques with a similar risk of severe complications.

CCRT → Planned Neck Dissection の QOL

CCRT → Planned Neck Dissection の QOL

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

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

Head and neck squamous cell carcinoma from an unknown primary site

Background The purpose of this study is to present our experience treating patients with squamous cell carcinoma (SCC) from an unknown head and neck primary site and to determine whether a policy change eliminating the larynx and hypopharynx from the radiotherapy (RT) portals has impacted outcome. Methods One hundred seventy-nine patients received definitive RT with or without a neck dissection for SCC from an unknown head and neck primary site. RT was delivered to the ipsilateral neck alone or both sides of the neck and, usually, the potential mucosal primary sites. The median mucosal dose was 5670 cGy. The median neck dose was 6500 cGy. One hundred nine patients (61%) received a planned neck dissection. Results Mucosal control at 5 years was 92%. The mucosal control rate in patients with RT limited to the nasopharynx and oropharynx was 100%. The 5-year neck-control rates were as follows: N 1, 94%; N 2a, 98%; N 2b, 86%; N 2c, 86%; N 3, 57%; and overall, 81%. The 5-year cause-specific survival rates were as follows: N 1, 94%; N 2a, 88%; N 2b, 82%; N 2c, 71%; N 3, 48%; and overall, 73%. The 5-year overall survival rates were as follows: N 1, 50%; N 2a, 70%; N 2b, 59%; N 2c, 45%; N 3, 34%; and overall, 52%. Eleven patients (7%) developed severe complications. Conclusion RT alone or combined with neck dissection results in a high probability of cure with a low risk of severe complications. Eliminating the larynx and hypopharynx from the RT portals did not compromise outcome and likely reduces treatment toxicity.

Planned Neck Dissection after CCR for HNSCC: Is It Necessary

Planned Neck Dissection after CCR for HNSCC: Is It Necessary

Need for postradiotherapy neck dissection by tumor site and nodal stage for head and neck cancer.

5517 Background: “Planned” neck dissection is controversial in node-positive patients whose primary head and neck squamous cell cancers (HNSCC) are treated by definitive radiotherapy ± chemotherapy. This analysis was undertaken to assess the risk of withholding planned neck dissection in patients who obtain a complete nodal response to irradiation, and to determine the benefit of a neck dissection in less than complete responders by tumor site. Methods: This single-institution retrospective study included 935 patients with T any N1-3M0 HNSCC of the oropharynx, larynx or hypopharynx without prior nodal surgery who presented between 1994 and 2004. Control rates were determined by the Kaplan-Meier Method, comparisons of rates with the log-rank test and prognostic factors by univariate and Cox analyses. Results: Half the patients achieved a clinical (using high-quality CT) complete nodal response. There were 12% neck failures after definitive radiotherapy. Those who had complete clinical resolution of all nod...

Induction docetaxel, cisplatin, and cetuximab (TPE) followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locoregionally advanced head and neck cancer (HNC): Mature results with HPV analysis.

5515 Background: We report updated survival with human papillomavirus (HPV) status analysis, late toxicities and quality- of-life (QOL) from a phase II trial that incorporated cetuximab (E) into induction therapy and subsequent concomitant chemoradiotherapy of HNC (ASCO 2008;A6002). Methods: Patients (pts) had previously untreated, stage III or IVA-B HNC (including squamous and undifferentiated histologies), ECOG performance status 0-1, and adequate laboratory parameters. Treatment consisted of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and E 250 mg/m2 days 1,8, and 15 (after an initial dose of 400 mg/m2 on cycle 1, day 1), termed “TPE” and repeated every 21 days x 3 cycles, followed by radiotherapy to 70 Gy (2 Gy/day) with concurrent cisplatin 30 mg/m2 and E 250 mg/m2 weekly (“XPE”), and maintenance E for 6 months (mo). QOL was assessed using FACT-HN. P16 and HPV in situ hybridization was done on baseline tissue. Results: Of 39 enrolled pts, 35 had stage IV disease. Primary sites were the oropharynx, 23; larynx, 5; hypopharynx, 3, oral cavity, 3; nasopharynx, 3; and unknown, 2. There were 28 active, 6 former, 5 never smokers; all smokers but 3 had >= 20 pack-year history. 2/3 planned neck dissections showed a pCR. With a median follow-up of 36 months, 2- and 3-year PFS was 70% and 67%, respectively; 2-and 3-year OS was 77%. HPV positivity was found in 67% of 27 evaluable tumor specimens, and did not alter PFS or OS. Recurrence in 12 pts was locoregional only in 8 pts, including local only (3), regional only (3), local and regional (2), distant only in 3, and locoregional and distant in 1. Of 4 pts who underwent salvage surgery, 2 were rendered disease free. Late toxicities included gr 2 neuropathy (2), chondronecrosis (1), and gr 3 laryngeal edema (1). No progression-free pt is G-tube dependent. FACT-HN showed a significant decrement at 3 mo after XPE, with return to baseline at 1 year. Conclusions: This E-based regimen has excellent long-term survival, safety and QOL and warrants further evaluation in both HPV positive and negative HNC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb

Clinical Usefulness of [(18)F] Fluoro-2-Deoxy- d-Glucose Uptake in 178 Head-and-Neck Cancer Patients With Nodal Metastasis Treated With Definitive Chemoradiotherapy: Consideration of Its Prognostic Value and Ability to Provide Guidance for Optimal Selection of Patients for Planned Neck Dissection

To evaluate the clinical effectiveness of pretreatment [18F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. The patients with a nodal SUV≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p=.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p=.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p=.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p=.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p=.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection.

Abstract 3286: Overexpression of cornulin in histologically normal adjacent tissue predicts occult nodal metastases in head and neck cancer patients

Abstract As with many epithelial cancers, presence of nodal metastases in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) predicts early recurrence and poor survival. Determination of occult metastases in the clinically N-zero (cN0) patient remains problematic and therefore prophylactic neck dissections are routinely performed for high risk cN0 patients. A cohort of 7 cN0 HNSCC patients who subsequently underwent planned neck dissection as part of their treatment was selected. Snap frozen tissue was enriched for tumor and adjacent normal tissue by laser capture microdissection. Total protein was extracted and separated by saturation-labeling 2D difference in-gel electrophoresis (2D-DIGE). Significance analysis of Microarray (SAM) method was used to evaluate for differential protein expression between patients with (n=3) and without (n=4) occult nodal metastases on neck dissection pathologic evaluation. Spot maps were generated for 14 gels (7 HNSCC, 7 normal) and relative abundance values calculated for each of 662 protein spots common to &amp;gt;90% of gels. A 5% false discovery rate and 2-fold change were used as criteria for significance in the defintion of candidate biomarkers. Protein spots meeting these criteria were then extracted, digested and analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. For tumor tissue, there was no significant difference between groups. There were considerable differences in protein expression for normal adjacent tissue between patients with and without occult metastases, with 60 spots meeting criteria for significance (FDR&amp;lt;0.05). There were 31 proteins underexpressed in occult metastases patients, with the top candidate being 11.9 fold lower in the occult metastasis group (adjusted q&amp;lt;0.001). There were 29 proteins overexpressed, with the top candidate being 6.6 fold higher in the occult metastasis group (adjusted q&amp;lt;0.001). This protein was identified as Cornulin, a 53 kDa calcium-binding protein of the s100 family recently identified as a novel HNSCC biomarker. Cornulin plays a known role as a cornification chaperone that is protective against acid stress in squamous epithelium. It is possible that elevated cornulin in surrounding normal tissue may reflect ongoing epithelial injury, predisposing developing tumors to aggressive behavior. In conclusion, we have identified overexpression of cornulin in adjacent normal tissue as a novel biomarker for tumors with occult metastases in the cN0 HNSCC patient population. Additionally, these data highlight the role that tumor-stroma interactions may play in the development of early nodal metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3286.