The acquisition and maintenance of skills in transoral microlaryngeal surgery requires extended practice. Effective mentoring of such single-operator procedures is not possible, making it important for trainee surgeons to acquire basic skills outside of the operating room before participating in procedures on patients. Currently available training simulators use either synthetic materials or human tissue, both of which have limitations. We have designed a hybrid simulator that incorporates a porcine larynx in to an airway training manikin, providing both accurate airway anatomy and natural tissue handling characteristics. This model allows training in the skills required for suspension laryngoscopy and the resection of laryngeal lesions. Further applications could include development of surgical techniques and instruments, and use in accreditation of training and revalidation of trained surgeons.
Surgical simulation; endolaryngeal surgery; manikin; surgical training; microlaryngeal surgery
Assessment of outcomes after craniofacial surgery for skull base tumors poses unique challenges because of the rarity of the problem and heterogeneity in clinical behavior of these tumors. Collaborative studies of outcome provide an opportunity for meaningful analysis of not just tumor-related outcome, but also quality of life after treatment in these patients. This article introduces the use of a Web-based data collection method that can function as a collaborative registry and a tool for collection of quality of life data.
Skull base neoplasms/surgery; questionnaires; neoplasms/psychology; international cooperation; software design
While obesity increases risk and negatively impacts survival for many malignancies, the prognostic implications in squamous cell carcinoma (SCC) of the oral tongue, a disease often associated with pre-diagnosis weight loss, are unknown.
Patients with T1–T2 oral tongue SCC underwent curative-intent resection in this single-institution study. All patients underwent nutritional assessment prior to surgery. Body mass index (BMI) was calculated from measured height and weight and categorized as obese (≥30 kg/m2), overweight (25 to 29.9 kg/m2), or normal (18.5 to 24.9 kg/m2). Clinical outcomes including disease specific survival (DSS), recurrence free survival (RFS), and overall survival (OS), were compared by BMI group using Cox regression.
From 2000–2009, 155 patients (90 men, 65 women) of median age 57 (range 18 to 86) were included. Baseline characteristics were similar by BMI group. Obesity was significantly associated with adverse DSS compared with normal weight in univariable (hazard ratio [HR] = 2.65, 95% confidence interval [CI], 1.07 to 6.59; P = .04) and multivariable analyses (HR = 5.01; 95% CI, 1.69 to 14.81; P = .004). A consistent association was seen between obesity and worse RFS (HR =1.87; 95% CI, .90 to 3.88) and between obesity and worse OS (HR=2.03; 95% CI, .88 to 4.65) though without reaching statistical significance (P = .09 and P = .10 respectively) in multivariable analyses.
In this retrospective study, obesity was an adverse independent prognostic variable. This association may not have been previously appreciated due to confounding by multiple factors including pre-diagnosis weight loss.
obesity; tongue neoplasms; prognosis; body mass index; head and neck neoplasms; squamous cell carcinoma of the head and neck
To use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and evaluating IVIM efficacy in predicting outcome.
Sixteen patients with HN cancer underwent IVIM DWI on a 1.5T MRI scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
In comparison to metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (p<0.0009), and lower diffusion coefficient (D) (p<0.0002). Patients with lower standard deviation for D had prolonged PFS and OS (p<0.05).
Pretreatment IVIM measures were feasible in investigating the physiological differences between the two tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.
Intravoxel incoherent motion imaging (IVIM); head and neck (HN) cancer; primary tumor; metastatic neck node
The objective of this study was to determine the prognostic significance of viable tumor in post-chemoradiation neck dissection specimens in patients with squamous cell carcinoma of the laryngopharynx.
Retrospective analysis identified 181 patients treated with primary concurrent chemoradiation for carcinoma of the laryngopharynx at Memorial Sloan-Kettering Cancer Center between the years 1995 and 2005. Of these, 56 patients had a comprehensive neck dissection either as a planned or salvage procedure. Neck dissection specimens were analyzed by a single pathologist for the presence of viable tumor. The presence of viable tumor was correlated to the timing of neck dissection after chemoradiation and to tumor response. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by the Kaplan–Meier method, and correlation to tumor viability was determined with the log-rank test.
Nineteen (33%) patients had viable tumor in their neck dissection specimens. Viable tumor was higher in patients who had a less-than-complete response to chemoradiation compared with those who had a complete response (42% vs 25%, p = .1). There was no correlation to timing of neck dissection. The 5-year OS, DSS, and RFS were significantly lower in patients who had viable tumor in their neck dissection specimens (OS 49% vs 93%, p = .0005; DSS 56% versus 93%, p = .003; RFS 40% vs 75%, p = .004).
Patients with viable tumor in postchemoradiation neck dissection specimens had a poorer outcome compared with patients with no viable tumor.
viable tumor; chemoradiation; neck dissection; prognosis
The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [1H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Pretreatment DCE-MRI and 1H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the “endogenous marker” of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, 1H-MRS, and molecular marker data.
A significant correlation was observed between DCE-MRI parameter std(kep) and VEGF IHC expression level (rho = 0.81, p = 0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(Ktrans) and std(ve) (rho = −0.71; p = 0.004, and rho = −0.73; p = 0.003, respectively). Other DCE-MRI, 1H-MRS and IHC values did not show significant correlation.
The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; molecular markers
Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB.
Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients.
Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis.
Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.
nose neoplasms/mortality/pathology/surgery/*therapy; esthesioneuroblastoma; olfactory/*therapy; combined modality therapy; radiotherapy; adjuvant; survival analysis
Dynamic contrast-enhanced-MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of the present study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery.
Methods and Materials
Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using Tofts model. DCE-MRI parameters were related to treatment outcome (progression free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD) or dead of other causes (DOC). Prognostic significance was assessed using the log rank test for single variables and Cox proportional hazards regression for combinations of variables.
At last clinical follow-up, for stage III, all 12 pts were NED, for stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression skewness of Ktrans was the strongest predictor for stage IV patients (PFS and OS: p<0.001).
Our study shows that skewness of Ktrans was the strongest predictor of PFS and OS in stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.
Dynamic Contrast Enhanced-MRI (DCE-MRI); head and neck squamous cell carcinoma (HNSCC); volume transfer constant (Ktrans)
To correlate proton magnetic resonance spectroscopy (1H-MRS), dynamic contrast-enhanced MRI (DCE-MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in nodal metastases of patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging (MMI) was evaluated for its efficacy in predicting short-term response to treatment.
Methods and Materials
Metastatic neck nodes were imaged with 1H-MRS, DCE-MRI and 18F-FDG PET in 16 patients with newly diagnosed HNSCC before treatment. Short-term radiological response was evaluated at 3–4 months. The correlations between 1H-MRS (choline concentration, Cho/W), DCE-MRI (volume transfer constant, Ktrans; volume fraction of the extravascular extracellular space, ve; and redistribution rate constant, kep) and 18F-FDG PET (standard uptake value, SUV; and total lesion glycolysis, TLG) were calculated using non-parametric Spearman rank correlation. To predict the short-term response, logistic regression analysis was performed.
A significant positive correlation was found between Cho/W and TLG (ρ = 0.599, p = 0.031). Cho/W correlated negatively with heterogeneity measures std(ve) (ρ = −0.691, p = 0.004) and std(kep) (ρ = −0.704, p = 0.003). SUVmax values correlated strongly with MRI tumor volume (ρ = 0.643, p = 0.007). Logistic regression indicated that std(Ktrans) and SUVmean were significant predictors of short-term response (p < 0.07).
Pretreatment multi-modality imaging using 1H-MRS, DCE-MRI and 18F-FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and 18F-FDG PET parameters were predictive of short-term response to treatment.
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; 18F-FDG PET; short-term treatment response
Abnormalities in cell cycle regulation, tumor suppressor gene functions and apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28 in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to immunohistochemistry using antibodies against p16, p53, and bcl-2. The results were correlated with histological features and survival data. Expressions of p16, p53, and bcl-2 proteins were seen in 25% (N = 19/76), 21% (N = 16/76), and 74% (N = 56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was associated with significantly longer overall and disease specific survival (3.3 vs. 1.5 years, P ≤ 0.05). Expression of p16 was increasingly lost, from 32% in initial tumors to 12% in recurrent and 15% in metastatic tumors (P = 0.06). Tumors comprised of undifferentiated cells were significantly more p53 positive than epithelioid or spindle cells (80% vs. 33%, P = 0.02). Expression of these markers did not correlate with necrosis, or vascular and/or deep tissue invasion. Expression of bcl-2 is associated with better survival in MM. Loss of p16 was seen with tumor progression whereas aberrant p53 expression was frequent in undifferentiated tumor cells.
Mucosal melanoma; Head and neck; p16; p53; bcl-2
Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). The objective of this study was to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine (RAI) therapy.
Fifty-two patients with distant metastases from thyroid cancer diagnosed before thyroid surgery (n=32) or on a postoperative RAI scan after thyroid surgery (n=20) were identified from a database of patients with WDTC treated between 1985 and 2005. The median age was 58 years (range 12–83 years), with a male-to-female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy and two (4%) had thyroid lobectomy, and three patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival were calculated by the Kaplan–Meier method. Factors predictive of the outcome were determined by univariate and multivariate analyses.
Thirty-nine patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in nine, mediastinum in one, pyriform sinus in one and skin in one, and one patient had synchronous lung, bone, and intracerebral metastases. After thyroid surgery, 47 patients (90%) were treated with RAI alone, and 2 patients had external beam radiation in addition to RAI. With a median follow-up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases were predictive of lower 5-year DSS (56% vs. 100%, p<0.001; 50% vs. 70%, p=0.004; and 46% vs. 75%, p=0.013, respectively).
Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome.
The purpose of this study was to determine the incidence of neck metastasis in hard palate and maxillary alveolus squamous cell carcinoma (SCC) and to identify factors predictive of regional failure.
In 139 patients treated for SCC of the hard palate and maxillary alveolus (from 1985–2006), the incidence rates of regional metastasis at presentation and at recurrence were calculated. Factors predictive of regional recurrence-free survival were identified on Cox multivariable regression analysis.
Regional failure occurred in 28.4% of patients and was significantly associated with pathologic T classification, ranging from 18.7% (pT1) to 37.3% (pT4). T classification was an independent predictor of regional recurrence-free survival (RRFS) on multivariable analysis. Most patients (65.6%) with regional recurrence were not able to be salvaged.
Patients with T2 to T4 primary tumors of the hard palate and maxillary alveolus exhibited high rates of regional failure. In most cases, successful salvage was not achieved. Elective treatment of the neck with surgery or radiation is therefore recommended.
cervical; regional; neck; metastases; hard palate; alveolus; gingiva
Patients with head and neck squamous cell carcinoma (HNSCC) are at significantly elevated risk of second primary malignancies (SPM), most commonly within the head and neck, lung, and esophagus (HNLE). Our objectives were to quantify the excess risk of SPM across all anatomic sites in which SPM risk is meaningfully elevated, including non-HNLE sites, in a large cohort of US patients.
Population-based analysis of 75,087 patients with HNSCC in the SEER program, quantifying excess SPM risk by integrating relative (standardized incidence ratio; SIR) and absolute (excess absolute risk per 10,000 person-years at risk; EAR) statistics.
In HNSCC patients, the SIR of a second primary solid cancer was 2.2 (95% CI 2.1–2.2), corresponding to EAR of 167.7 additional cases per 10,000 person-years at risk. Over 1 year, 60 patients would need to be followed to observe one excess SPM. Lung cancer burden was most markedly elevated in absolute terms (EAR = 75.2), followed by HN (EAR = 59.8), esophageal (EAR = 14.2), and colorectal (EAR = 4.3) cancers. Lesser but significant excess risks were also observed for cancers of the bladder, liver, stomach, pancreas, kidney, salivary glands, nasopharynx, uterine cervix, and lymphoma.
Data from a large population-based US cohort reveals that HNSCC patients experience markedly excess risk of SPM, predominantly in the HNLE sites. Furthermore, the risk of SPM is also meaningfully elevated, although to a lesser degree, in multiple other tobacco-associated sites.
Second primary; Malignancy; Cancer; Head and neck; Lung; Esophagus; Colon
Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) –associated oropharyngeal SCC.
Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression.
In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, −4.6%; P = .03).
In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.
To compare outcomes of a pediatric cohort of patients compared with a matched cohort of adult patients, all diagnosed as having squamous cell carcinoma (SCC) of the oral tongue. Outcomes of oral cancer in pediatric patients have not been studied, to our knowledge.
Retrospective matched-pair cohort study.
Memorial Sloan-Kettering Cancer Center, New York, New York.
A total of 10 pediatric and 40 adult patients diagnosed as having SCC of the oral tongue.
Main Outcome Measures
Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS).
The 5-year OS was equivalent in the 2 groups: 70% in the pediatric group and 64% in the adult group (P=.97). The 5-year DSS was also equivalent: 80% in the pediatric group and 76% in the adult group (P=.90). The 5-year RFS was 70% in the pediatric group and 78% in the adult group (P=.54).
When pediatric and adult patients were matched for sex, tobacco use history, TNM status, surgical procedure, and adjuvant radiotherapy, outcomes for OS, DSS, and RFS were equivalent. Pediatric patients with SCC of the oral tongue should be treated similarly to adult patients.
We sought to better define the results of anterior skull base surgery in pediatric and young adult patients. We performed a single-institution, retrospective cohort study in a tertiary-care academic cancer center. Between 1973 and 2005, 234 patients underwent anterior skull base surgery at Memorial Sloan-Kettering Cancer Center. Of these, 19 patients were <21 years of age. Surgical indications, findings, and complications were reviewed. Survival outcomes were analyzed using the Kaplan-Meier method and compared with patients ≥21 years old. Nineteen patients <21 years old underwent a total of 20 procedures for lesions of the anterior skull base. Sarcoma was the most common indication for surgery including 6 (32%) patients treated for radiation-induced malignancies. Minor complications were noted with 6 (30%) procedures. There were no major complications and no perioperative deaths. The difference in 3-year recurrence-free (68% versus 59%; p = 0.623) and overall survival (83% versus 66%; p = 0.309) compared with patients ≥21 years old did not reach statistical significance. Anterior skull base surgery is well tolerated in pediatric and young adult patients <21 years of age. Survival is comparable to older patients treated similarly and appears strongly influenced by histology.
Craniofacial resection; skull base surgery; pediatric; complications; survival
The present study determines the feasibility of generating an average arterial input function (Avg-AIF) from a limited population of patients with neck nodal metastases to be used for pharmacokinetic modeling of dynamic contrast-enhanced MRI (DCE-MRI) data in clinical trials of larger populations.
Twenty patients (mean age 50 years [range 27–77 years]) with neck nodal metastases underwent pretreatment DCE-MRI studies with a temporal resolution of 3.75 to 7.5 sec on a 1.5T clinical MRI scanner. Eleven individual AIFs (Ind-AIFs) met the criteria of expected enhancement pattern and were used to generate Avg-AIF. Tofts model was used to calculate pharmacokinetic DCE-MRI parameters. Bland-Altman plots and paired Student t-tests were used to describe significant differences between the pharmacokinetic parameters obtained from individual and average AIFs.
Ind-AIFs obtained from eleven patients were used to calculate the Avg-AIF. No overall significant difference (bias) was observed for the transfer constant (Ktrans) measured with Ind-AIFs compared to Avg-AIF (p = 0.20 for region-of-interest (ROI) analysis and p = 0.18 for histogram median analysis). Similarly, no overall significant difference was observed for interstitial fluid space volume fraction (ve) measured with Ind-AIFs compared to Avg-AIF (p = 0.48 for ROI analysis and p = 0.93 for histogram median analysis). However, the Bland-Altman plot suggests that as Ktrans increases, the Ind-AIF estimates tend to become proportionally higher than the Avg-AIF estimates.
We found no statistically significant overall bias in Ktrans or ve estimates derived from Avg-AIF, generated from a limited population, as compared with Ind-AIFs.
However, further study is needed to determine whether calibration is needed across the range of Ktrans. The Avg-AIF obtained from a limited population may be used for pharmacokinetic modeling of DCE-MRI data in larger population studies with neck nodal metastases. Further validation of the Avg-AIF approach with a larger population and in multiple regions is desirable.