Robert J. Sinard

Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas

PURPOSE High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC. PATIENTS AND METHODS EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points. RESULTS Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors. CONCLUSION High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Systematic management of chyle fistula: The Southwestern experience and review of the literature:

Postoperative cervical chyle fistula after neck dissection is a complication with potentially serious morbidity. Once it is recognized, treatment decisions to optimize patient care can be difficult. Different management strategies have been advocated on the basis of institutional and personal experience. In this study we comprehensively review the published protocols and retrospectively review our experience in the management of 15 patients with chyle fistula. All patients in this study were given a trial of nonoperative management with nutritional modification, pressure dressings, and closed drainage. Medical management ultimately failed in 3 patients (20%). Two patients had prolonged courses of medical management with associated complications. An analysis of our data supports early operative intervention if the peak 24hour drainage is greater than 1000 mL without a prompt response to medical management. Persistent low-output drainage after 10 days is associated with a prolonged management course and treatment-related complications. Optimal treatment of these patients is unclear. (Otolaryngol Head Neck Surg 2000;122:31–8.)

Survival impact of planned restaging and early surgical salvage following definitive chemoradiation for locally advanced squamous cell carcinomas of the oropharynx and hypopharynx

Objectives:Patients who have received definitive radiation therapy (RT) for a nonlaryngeal T3/4 head and neck squamous cell carcinoma have a limited opportunity for post-RT surgical salvage. The authors reviewed the practice of planned post-RT restaging to determine its impact on the success of early surgical salvage. Methods:A retrospective review was performed for patients with resectable T3/4 cancers of the oropharynx and hypopharynx treated with RT ± chemotherapy who underwent planned restaging clinically, radiographically (CT or MRI), and by direct laryngoscopy with biopsy at 4 to 8 weeks post-RT. Chemotherapy was given as induction, concurrently, or both. Neck dissection was performed at time of restaging in patients with primary tumor control and initial N2/N3 neck disease or persistent lymphadenopathy. Results:A total of 54 patients had a median follow-up of 34.7 months (range, 7.6–97.8 months). Forty-two patients (78.8%) achieved a complete response (CR) at the primary site immediately after RT. Six developed late local failure at 9 to 61 months, of whom 2 were successfully salvaged. The ultimate 2-year local control among patients with initial CR was 94.8%. The 2-year organ preservation, disease-free survival, and overall survival (OS) rates were was 92.5%, 87%, and 90%, respectively. Twelve patients did not achieve initial CR. Two patients with bulky stage IV disease had unresectable cancers. Ten underwent immediate surgical salvage and 7 achieved local control (1 of whom developed distant metastases) whereas 3 had continued local failure. For patients without initial CR, the 2-year ultimate local control rate was 46.7% and OS was 46.8%. For all patients, overall 2-year local control, organ preservation, and OS rates were 85.6%, 75.6%, and 81.8% respectively. The rate of local failure-free organ preservation was 71.5%. Conclusion:For patients with T3/4 resectable nonlaryngeal head and neck cancers, planned clinical, radiographic, and pathologic restaging at 1 to 2 months after definitive RT provides the opportunity for early surgical salvage in those who fail at the primary site. This practice produces improved overall local control and survival rates compared with the literature reports for delayed attempted salvage with timing based on the findings of routine postradiation clinical surveillance. Future efforts may focus on the improved selection of patients who would be most likely to require early surgical intervention.

Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

BACKGROUND Our previous study has shown that nuclear factor-kappa B (NF-kappaB)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-kappaB inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity. MATERIALS AND METHODS Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-kappaB-associated genes. RESULTS Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-kappaB and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis. CONCLUSION Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.

Impact of secondary lymphedema after head and neck cancer treatment on symptoms, functional status, and quality of life

Lymphedema may disrupt local function and affect quality of life (QOL) in patients with head and neck cancer. The purpose of this study was to examine the associations among severity of internal and external lymphedema, symptoms, functional status, and QOL in patients with head and neck cancer.

Reliability and validity of the Vanderbilt Head and Neck Symptom Survey: A tool to assess symptom burden in patients treated with chemoradiation

We describe the development and validation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), which was designed to screen for tumor‐ and treatment‐specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation (CCR).

Delayed regional metastasis from midfacial squamous carcinomas

Metastases from mucosal and cutaneous carcinomas can present in a delayed fashion, and this late presentation may confer a different prognosis after conventional treatment.

Factors Associated With External and Internal Lymphedema in Patients With Head-and-Neck Cancer

PURPOSE The purpose of this study was to examine factors associated with the presence of secondary external and internal lymphedema in patients with head-and-neck cancer (HNC). METHODS AND MATERIALS The sample included 81 patients ≥3 months after HNC treatment. Physical and endoscopic examinations were conducted to determine if participants had external, internal, and/or combined head-and-neck lymphedema. Logistic regression analysis was used to examine the factors associated with the presence of lymphedema. RESULTS The following factors were statistically significantly associated with presence of lymphedema: (1) location of tumor associated with presence of external (P=.009) and combined lymphedema (P=.032); (2) time since end of HNC treatment associated with presence of external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation therapy (P=.010) and days of radiation (P=.017) associated with the presence of combined lymphedema; (4) radiation status of surgical bed was associated with the presence of internal lymphedema, including surgery with postoperative radiation (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number of treatment modalities associated with external (P=.002), internal (P=.039), and combined lymphedema (P=.004). No demographic, health behavior-related, or comorbidity factors were associated with the presence of lymphedema in the sample. CONCLUSIONS Select tumor and treatment parameters are associated with increased occurrence of lymphedema in patients with HNC. Larger and longitudinal studies are needed to identify adjusted effects and causative risk factors contributing to the development of lymphedema in patients with HNC.

Disease homogeneity and treatment heterogeneity in idiopathic subglottic stenosis

Idiopathic subglottic stenosis (iSGS) is a rare and potentially life‐threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes.

Evolution of clinical trials in head and neck cancer

The treatment paradigm for locally advanced head and neck cancers has evolved over the past two decades as the role of chemotherapy has been substantiated by clinical trials. Presently, concurrent chemoradiation is considered a standard treatment option for patients with resectable head and neck tumors desiring an organ preservation approach, as well as for patients with locally advanced nasopharyngeal cancers and patients in the postoperative setting who are at high risk for recurrence. The addition of a taxane to induction chemotherapy appears to improve efficacy over cisplatin and 5-FU. Targeted biologic therapies such as the monoclonal antibody Cetuximab has demonstrated efficacy with radiation that appear comparable to chemoradiation combinations and has a favorable toxicity profile. This review will discuss key clinical trials supporting the current standard of care. Emerging new technologies such as intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) will also be reviewed. Functional assessments and quality of life issues will be addressed.