Regional diagnostic rates, treatments, and outcomes among patients with invasive ductal carcinoma.

BACKGROUND: The association between regional breast cancer diagnostic rates, treatments, and outcomes is unclear. We sought to investigate the management and survival of women with invasive ductal carcinoma (IDC) from geographic regions with variable rates of diagnosis. METHODS: Data on women diagnosed with IDC years 2009-2010 were obtained from the Surveillance, Epidemiology, and End Results database. Patients were divided into quartiles based on the IDC diagnostic rate within their county of residence. Chi-square and one-way analysis of variance (ANOVA) analyses tested the association between patient and clinical characteristics and the diagnostic rate quartiles. Cox regression analyses compared survival between the quartiles. RESULTS: Among the 83,375 patients included, the mean age was 60.8 y and 70.9% were white. Patients residing in counties with the highest diagnostic rates were more frequently white, employed, educated, and wealthier and more often received adjuvant radiation following both partial mastectomy for localized disease and complete mastectomy for advanced disease compared to patients in counties with the lowest diagnostic rates. The highest diagnostic rate quartile had 10% decreased odds of death compared to the lower quartile (hazard ratio: 0.897; 95% confidence interval: 0.832-0.966). However, after adjustment for socioeconomic variables, survival was comparable (hazard ratio: 0.916; 95% confidence interval: 0.835-1.003). CONCLUSIONS: Regional variation in IDC diagnostic rates is associated with differences in socioeconomic status, grade, stage, and treatment. Patients from regions with the highest rates of diagnosis may have improved access to evidence-based care and resultant superior survival. Enhancing access to care may improve outcomes of patients residing in regions where breast cancer is diagnosed less frequently.

Unilateral Vocal Cord Motion Impairment After 1 Dose of Vincristine: Case Report and Literature Review.

Vocal cord paralysis after administration of the chemotherapeutic agent vincristine is a rare occurrence. Most occurrences are bilateral. Of the 24 cases referenced in this article, 19 are children. In all the reported cases, symptoms have occurred after multiple doses of vincristine have been administered. The authors report a case of a 39-year-old woman with unilateral vocal cord motion impairment occurring 3 days after the administration of the first dose of vincristine. This is the first case of vocal cord motion impairment reported after the administration of only 1 dose of this drug.

Asymptomatic Deep Peroneal Vein Thrombosis During Free Fibula Flap Harvest: A Review of the Literature, Strategies for Preoperative Assessment, and an Algorithm for Reconstruction.

The free fibula flap is the preferred reconstructive method for oncologic defects of the mandible. Arterial inflow of the extremity is routinely evaluated with several modalities; however, venous screening is rarely performed. Patients with cancer are at elevated risk of occult deep venous thrombosis (DVT). An asymptomatic thrombus encountered during free fibula reconstruction is a serious concern. Although such cases have been reported, we suspect the incidence of DVT during fibula free flap harvest is underappreciated. This monograph uses a case example to review risk factors for occult DVT, present a strategy for preoperative assessment, and provide a reconstructive algorithm to for mandibular reconstruction in such instances.

Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer.

BACKGROUND: In head and neck cancer patients prior to treatment, dysphagia noted by patients is more common than aspiration on formal swallow studies. The authors hypothesized that patient-reported dysphagia impacts multiple domains of quality of life (QOL) and predicts disease recurrence and disease-related death. METHODS: The Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, and the EuroQOL-5D-3L were administered to 159 patients before treatment with curative intent in this prospective cohort study. Logistic regression analysis evaluated associations among clinical and subjective measures. Multivariable competing risk regression tested the impact of clinical, tumor, and patient-reported measures on survival. RESULTS: Baseline dysphagia, pain, and diminished patient-reported health state were found to be closely associated with weight loss before treatment and advanced T classification. However, only 58% of patients (23 of 40 patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found to be associated with pain and/or diminished patient-reported health state, independent of weight loss. Female patients were more likely to report pain and dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to be predictive of disease recurrence and disease-related death, adjusting for T and N classifications, ECOG performance status, smoking status, and weight loss, and accounting for competing risks of death (recurrence-free survival: hazards ratio, 3.8 [95% confidence interval, 1.7-8.4; P = .001] and disease-related death: hazards ratio, 4.2 [95% confidence interval, 1.04-5; P = .004]). CONCLUSIONS: Baseline dysphagia affects multiple domains of QOL and general health perceptions in patients with head and neck cancer prior to treatment. A dysphagia measure captures the effort of maintaining nutrition, and identifies patients predisposed to disease recurrence and disease-related death.

Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021. SETTING: Single-institution NCI-Designated Comprehensive Cancer Center. METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). RESULTS: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). CONCLUSIONS: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Malignant transformation of respiratory papillomatosis in a solid-organ transplant patient: case report and literature review.

We report the case of a 77-year-old non-smoker and non-drinker with a solid-organ transplant who had malignant transformation of respiratory papillomatosis 3 years after the initial diagnosis of this benign lesion. This is the first case reported in the literature of malignant transformation of respiratory papillomatosis in a solid-organ transplant patient. Virus-associated cutaneous cancers occur more frequently and aggressively in solid-organ transplant patients. There may be a higher rate of malignant transformation of respiratory papillomatosis in immunosuppressed patients, as this is a virus-associated disease. Closer observation, airway evaluation with laryngoscopy and tracheobronchoscopy, and interval biopsies of immunosuppressed patients with respiratory papillomatosis is recommended.

Analysis of Unmet Information Needs Among Patients With Thyroid Cancer.

Importance: Counseling prior to thyroid cancer (TC) treatment is an essential component of informed consent. An informed patient affects treatment-related expectations and patient engagement, factors that contribute significantly to patient-reported quality-of-life outcomes. Objective: To describe experiences with pretreatment counseling among survivors of TC and to test factors associated with self-reported treatment meeting expectations. Design, Setting, and Participants: A cross-sectional survey was administered between October 18, 2019, and February 8, 2020, to members of ThyCa: Thyroid Cancer Survivors' Association Inc, and to individuals accessing the public-facing ThyCa website. Survey respondents were asked 55 questions, including 4 free-text questions and 2 multiple-choice questions about pretreatment counseling. Main Outcomes and Measures: Respondents self-reported (1) their unmet information needs, (2) rates of treatment meeting expectations, and (3) rates of treatment understanding. A mixed-methods analysis was performed, including qualitative content analysis of free-text responses and multivariable logistic regression of factors associated with self-reported levels of treatment meeting expectations. Results: Of the 1412 survey respondents, 1249 were women (88.4%). The median age at diagnosis was 48 years (range, 18-85 years), and the median age at the time of survey completion was 60 years (range, 18-87 years). A total of 1259 respondents (89.2%) provided free-text responses to the question, "What would you tell someone newly diagnosed with your same condition?" Of these individuals, 526 (37.2%) reported inadequate pretreatment plan understanding and 578 (40.9%) reported that their treatment experience did not meet their expectations. Treatment met expectations for only 95 respondents (18.1%) reporting an inadequate pretreatment plan understanding. Of the 526 survivors of TC reporting a lack of understanding, 473 (90.0%) provided additional textual comments, most commonly in the categories of postoperative treatment, surveillance, and treatment effects. On multivariable logistic regression, self-reported failure to have an understanding of TC treatment was independently associated with failure of treatment to meet expectations (odds ratio, 5.1 [95% CI, 3.7-6.9]). Patients reporting a full understanding of their treatment plan were 5-fold more likely to indicate that their initial treatment experience was on par with expectations, independent of reported postoperative complications, age, sex, and other potential confounders. Conclusions and Relevance: In this survey study, a substantial proportion of survivors of TC reported inadequate pretreatment understanding. This gap in understanding was associated with high levels of self-reported failure of treatment to meet expectations, which in turn is associated in other studies with poorer patient-reported quality-of-life outcomes. These outcomes may be improved by addressing gaps in patient understanding so expectations more closely match TC diagnosis and treatment pathways.

Effect of Sentinel Lymph Node Biopsy and LVI on Merkel Cell Carcinoma Prognosis and Treatment.

OBJECTIVE: Prognostic factors and optimal treatment approaches for Merkel cell carcinoma (MCC) remain uncertain. This study evaluated the influences of sentinel lymph node (SLN) biopsy and lymphovascular invasion (LVI) on treatment planning and prognosis. STUDY DESIGN: Retrospective cohort study. METHODS: Stage 1 to 3 MCC patients treated 2005 to 2018. Predictors of nodal radiation were tested using logistic regression. Predictors of recurrence-free, disease-specific, and overall survival were tested in Cox proportional hazard models. RESULTS: Of 122 patients, 99 were without clinically apparent nodal metastases. Of these, 76 (77%) underwent excision and SLN biopsy; 29% had metastasis in SLNs, including 20% of MCCs 1 cm or less. Primary tumor diameter, site, patient age, gender, and immunosuppressed status were not significantly associated with an involved SLN. Among patients who underwent SLN biopsy, 13 of 21 (62%) MCCs with LVI had cancer in SLNs compared with 14 of 44 (25.5%) without LVI (P = .003). Although local radiation was common, nodal radiation was infrequently employed in SLN negative (pathologic N0) patients (21.8% vs. 76.2% for patients with SLN metastases, P = .0001). Survival of patients with positive SLNs was unfavorable, regardless of completion lymphadenectomy and/or adjuvant radiation. After accounting for tumor (T) and node (N) classification, age, immunosuppression, and primary site, a positive SLN and LVI were independently associated with worse survival (LVI/recurrence-free survival [RFS]: hazard ratio [HR] 2.3 (1.04-5, P = .04; LVI/disease-specific survival [DSS]: HR 5.2 (1.8-15, P = .007); N1a vs. pN0/RFS HR 3.6 (1.42-9.3, P = .007); DSS HR5.0 (1.3-19, P = .17). CONCLUSION: SLN biopsy assists in risk stratification and radiation treatment planning in MCC. LVI and disease in SLNs, independently associated with worse survival, constitute markers of high-risk disease warranting consideration for investigational studies. LEVEL OF EVIDENCE: III Laryngoscope, 131:E828-E835, 2021.

Rapid recurrence in head and neck cancer: Underappreciated problem with poor outcome.

BACKGROUND: Rapid recurrence, defined as gross tumor recurrence after primary operation but prior to initiating postoperative radiation therapy (PORT), is underappreciated in head and neck cancer (HNC). METHODS: CT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed. RESULTS: A total of 194 patients with HNC were included. Rapid recurrence occurred in 39 patients (20%) with a median time from operation to CT simulation of 37 days. On multivariable analysis (MVA), extranodal extension (ENE) was the only predictor of rapid recurrence (P = .03). While rapid recurrence, ENE, and perineural invasion were all associated with poor overall survival (OS) on MVA, rapid recurrence was the strongest predictor (hazard ratio [HR] 5.47). CONCLUSION: Rapid recurrence occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT.

Risk groups of laryngeal cancer treated with chemoradiation according to nomogram scores - A pooled analysis of RTOG 0129 and 0522.

OBJECTIVES: To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS: Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively. RESULTS: The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome. CONCLUSIONS: We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.

How did we get here? Short history of COVID-19 and other coronavirus-related epidemics.

The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials.

Impact of primary tumor-specific growth rate on treatment failure for nonoropharyngeal head and neck cancers.

OBJECTIVES: To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC). METHODS: The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (< 2.18% per day). RESULTS: The median follow-up was 22 months (range: 1-86 months) and median time between diagnostic and simulation computed tomography scans was 22 days (range: 7-170 days). Median RT dose was 70 Gy (range: 60-79.2 Gy). Based on the 75th percentile TSGR, OS at median follow-up was 50.0% for the high TSGR group compared to 92.5% for the low TSGR group (HR [95% confidence interval (CI)] = 2.12[1.16-11.42], P = 0.018). There was a trend toward worse DFS at median follow-up for the high versus low TSGR groups, at 55.6% and 82.3%, respectively (HR [95% CI] = 2.29[0.82-6.38], P = 0.103). CONCLUSION: Our study contributes to growing literature on TSGR as a temporal biomarker in patients with non-OPSCC. Patients with high TSGR ≥2.18% per day have significantly worse OS compared to those with TSGR below this threshold. Efforts to address treatment initiation delays may benefit patients with particularly aggressive and rapidly growing tumors. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2378-2384, 2020.

Head and neck surgical oncology in the time of a pandemic: Subsite-specific triage guidelines during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel. METHODS: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular. RECOMMENDATIONS: Each subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred. CONCLUSION: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

Multimodal treatment for head and neck cancer.

Head and neck cancers are relatively less common tumors, but with complex anatomic and physiologic relationships to the structures from which they arise. Multimodal management is required for advanced stage disease, while single modality treatment is usually sufficient for early lesions. Treatment paradigms have shifted toward more functional preservation of speech and swallowing, when possible. Increased use of radiation, systemic/targeted therapies and function-preserving surgical approaches have allowed for organ preservation without compromising oncologic outcomes in properly selected patients.

Diverging incidence trends for larynx and tonsil cancer in low socioeconomic regions of the US.

OBJECTIVE: Oropharynx cancer incidence trends in low socioeconomic (SES) regions of the United States (US) have not been well described. Our objective was to describe tonsil cancer incidence trends in low SES regions, and compare observed trends with those for larynx cancer. MATERIALS AND METHODS: Age-adjusted incidence rates and trends for tonsil and larynx squamous cell carcinomas (2000-14) from Surveillance, Epidemiology, and End Results (SEER 18) were evaluated using SEER*Stat and Joinpoint 4.5.0.1. Annual percentage changes (APCs) were compared between low and high SES counties. The laryngeal cancer cohort was included as a comparator reflecting a tobacco-related malignancy. RESULTS: Tonsil cancer incidence trends increased at least as much in low SES as in high SES counties (APC/AAPC 4.4, 95%CI 2.4-6.4 versus APC/AAPC 2.9, 95%CI 2.4-3.3). Pairwise comparison confirmed no differences between incidence trends across SES quintiles for tonsil cancer incidence rates. In contrast, age-adjusted incidence rates of larynx cancer decreased in high SES counties (APC/AAPC -2.4, 95%CI -2.4 to -2.0, p < 0.001) and were stable in low SES counties (APC/AAPC -0.9, 95%CI -1.9 to 0.2, p = 0.10). Compared with larynx cancer patients, tonsil cancer patients in low SES regions were significantly more likely to be younger and white. CONCLUSION: In low SES US counties, tonsil cancer incidence rates increased from 2000 to 2014, while larynx cancer rates did not change, reflecting diverging trends for larynx and tonsil cancers. Tonsil cancer incidence rates are increasing in most US regions regardless of regional socioeconomic status. Prevention efforts should take these findings into account.

Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

OBJECTIVES: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment. MATERIALS AND METHODS: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation. RESULTS: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP. CONCLUSION: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation.

Otolaryngology-Related Disorders in Underserved Populations, Otolaryngology Training and Workforce Considerations in North America.

In North America, underserved and vulnerable populations experience poorer health outcomes despite greater per capita health care expenditures. Biologic, behavioral, and socioeconomic factors lead to more advanced disease presentation that may necessitate disparate treatment. Additionally, vulnerable populations are more likely to obtain care from low-volume providers, and are more likely to receive inappropriate care. Disparities in care are exacerbated by the distribution of the physician workforce and limited participation by physicians in the care of vulnerable populations. Multipronged strategies are needed to ameliorate observed disparities in care.

Effect of rural and urban geography on larynx cancer incidence and survival.

OBJECTIVES/HYPOTHESIS: Investigate the impact of rural geography on larynx cancer incidence and survival. STUDY DESIGN: Surveillance, Epidemiology, and End Results (SEER) database study. METHODS: Incidence and survival rates by Rural-Urban Continuum codes for larynx squamous cell carcinoma patients diagnosed from 2004 to 2012 were evaluated using SEER statistical software and Cox proportional hazards survival analysis. RESULTS: The lowest age-adjusted incidence rates for larynx cancer were seen in densely populated urban regions, with mean rates of 2.8 per 100,000 person years (95% confidence interval [CI]: 2.7-2.8); the highest were in the most rural areas, with mean rates of 5.3 per 100,000 person years (95% CI: 4.7-5.9). Nevertheless, of 23,659 larynx cancer patients diagnosed over this period, 19,556 (82.7%) arose in urban residents, compared with 1,428 or 6% from rural areas. Urban larynx cancer patients more likely lived in counties with an American College of Surgeons-approved cancer center and/or a fourfold greater otolaryngology physician supply. Nevertheless, frequency of advanced stage at initial presentation was similar. Cause-specific and overall survival were no different, both on univariable and multivariable analyses. CONCLUSIONS: Compared with urban populations, Rural populations are at greater risk of developing larynx cancer, but initial stage and survival after diagnosis are comparable. Priority should be given to prevention strategies to decrease incidence rates. LEVEL OF EVIDENCE: 4 Laryngoscope, 1874-1880, 2018.

Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and primarily when combined with standard therapy. The most common form of mutant EGFR (EGFRvIII) has been described in several cancers, chiefly glioblastoma. The present study was undertaken to determine the incidence of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on tumor growth in response to EGFR targeting. EXPERIMENTAL DESIGN: Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vector-transfected controls were compared for growth rates in vitro and in vivo as well as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/cetuximab/Erbitux. RESULTS: EGFRvIII expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells. CONCLUSIONS: EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.