ABSTRACT

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.

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.

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

Objective

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.

Design

Retrospective matched-pair cohort study.

Setting

Memorial Sloan-Kettering Cancer Center, New York, New York.

Patients

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).

Results

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).

Conclusions

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.

ABSTRACT

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.

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Purpose

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.

Results

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).

Conclusion

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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.