Treatment delay associated with alternative medicine use among veterans with head and neck cancer

BACKGROUND: Use of complementary and alternative medicine (CAM) is increasing in the United States. This study investigates whether the use of alternative medicine is associated with a delay of treatment in head and neck cancer. METHODS: This study used the records obtained from a large trial involving ambulatory care US veterans. Subjects completed a CAM utilization questionnaire. The primary outcome variable was the time duration from cancer diagnosis to the time of cancer treatment. RESULTS: Of veterans with head and neck cancer, 51% reported using some form of CAM, whereas 23% reported using a therapy classified as alternative medicine. Patients who used alternative medicine significantly delayed cancer treatment by 22 days compared with those who did not use alternative medicine (p = .05, 95% confidence interval [CI] = 0-44 days). CONCLUSIONS: CAM use is common in veterans with head and neck cancer. Use of alternative medicine was associated with a significant delay in cancer treatment.     

Prediction of survival in patients with head and neck cancer

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC) the estimated prognosis is usually based on the TNM classification. The relative weight of the three contributing parameters is often not completely clear. Moreover, the impact of other important clinical variables such as age, gender, prior malignancies, etc is very difficult to substantiate in daily clinical practice. The Cox-regression model allows us to estimate the effect of different variables simultaneously. The purpose of this study was to design a model for application in new HNSCC patients. In our historical data-base of patients with HNSCC, patient, treatment, and follow-up data are stored by trained oncological data managers. With these hospital-based data, we developed a statistical model for risk assessment and prediction of overall survival. This model serves in clinical decision making and appropriate counseling of patients with HNSCC. PATIENTS AND METHODS: All patients with HNSCC of the oral cavity, the pharynx, and the larynx diagnosed in our hospital between 1981 and 1998 were included. In these 1396 patients, the prognostic value of site of the primary tumor, age at diagnosis, gender, T-, N-, and M-stage, and prior malignancies were studied univariately by Kaplan-Meier curves and the log-rank test. The Cox-regression model was used to investigate the effect of these variables simultaneously on overall survival and to develop a prediction model for individual patients. RESULTS: In the univariate analyses, all variables except gender contributed significantly to overall survival. Their contribution remained significant in the multivariate Cox model. Based on the relative risks and the baseline survival curve, the expected survival for a new HNSCC patient can be calculated. CONCLUSIONS: It is possible to predict survival probabilities in a new patient with HNSCC based on historical results from a data-set analyzed with the Cox-regression model. The model is supplied with hospital-based data. Our model can be extended by other prognostic factors such as co-morbidity, histological data, molecular biology markers, etc. The results of the Cox-regression may be used in patient counseling, clinical decision making, and quality maintenance.     

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer

PURPOSE: The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck. METHODS: We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded. RESULTS: A total of 131 patients were analyzed. Seventy-nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year locoregional and neck progression-free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p =.02) and 99% versus 82% (p =.0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p =.53) or any other survival parameters with or without ND were observed. CONCLUSIONS: ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease-free with intensive concurrent chemoradiotherapy.     

Prediction of survival in patients with head and neck cancer using the histoculture drug response assay

BACKGROUND: Chemoresponse is a significant outcome predictor in patients with head and neck cancer, regardless of the treatment modality used. The histoculture drug response assay (HDRA) has been shown to be a reliable method for in vitro chemoresponse assessment. In this study, we have correlated the HDRA assessment with survival in patients with head and neck squamous cell carcinoma (HNSCC). METHOD: Tumor specimens from 41 of 42 patients undergoing treatment for HNSCC were successfully evaluated by the HDRA. Tumor tissue was histocultured on Gelfoam sponges gel in 24-well plates, followed by treatment with cisplatin (15 microg/mL) or 5-fluorouracil (40 microg/mL) in triplicate. A control group received no drug treatment. After completion of drug treatment, the relative cell survival in the tumors was determined using the MTT assay. The inhibition rate (IR) for each drug was calculated relative to the control for each case, and sensitivity was defined as a tumor IR of greater than 30%. Treatment was based on established protocols for the location and stage of the tumor and included surgery, radiation, and/or chemotherapy. Survival comparisons were performed using the generalized Wilcoxon test for the comparison of Kaplan-Meier survival curves. RESULTS: Resistance to 5-fluorouracil was present in 13 cases (32%), to cisplatinum in 13 cases (32%), and to both agents in 11 cases (27%). The 2-year cause-specific survival was significantly greater for patients sensitive to 5-fluorouracil (85% vs 64%; p =.04), cisplatinum (86% vs 64%; p =.05), or both agents (85% vs 63%; p =.01). The association between HDRA assessment of chemoresponse and clinical outcome remained significant even after controlling for the effects of TNM stage and the presence of recurrent cancer at presentation by multivariate analysis. CONCLUSIONS: Chemosensitivity determined by the HDRA seems to be a strong predictor of survival in patients with advanced HNSCC and should be considered further.     

Single‐marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase

Background

In accord with the cancer stem cell (CSC) theory, only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from head and neck squamous cell cancer (HNSCC). Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs.

Methods

Six primary HNSCCs were collected. Cells with high and low ALDH activity (ALDH^high/ALDH^low) were isolated. ALDH^high and ALDH^low populations were implanted into NOD/SCID mice and monitored for tumor development.

Results

ALDH^high cells represented a small percentage of the tumor cells (1% to 7.8%). ALDH^high cells formed tumors from as few as 500 cells in 24/45 implantations, whereas only 3/37 implantations of ALDH^low cells formed tumors.

Conclusions

ALDH^high cells comprise a subpopulation cells in HNSCCs that are tumorigenic and capable of producing tumors at very low numbers. This finding indicates that ALDH activity on its own is a highly selective marker for CSCs in HNSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Selective neck dissection in the management of the neck after (chemo)radiotherapy for advanced head and neck cancer. Proposal for a classification update

For patients with advanced regional disease, neck dissection following (chemo)radiotherapy remains controversial. Selective neck dissection (SND) was reported as suitable after chemoradiation in patients with advanced regional disease. Reduced morbidity represents the major advantage of SND. In a situation in which there is a major fibrosis around the previously invaded nodes, resection of 1 or more nonlymphatic structures may be required. The current classification of SND could be implemented by the addition of extended selective neck dissection (ESND). The standard basic procedures for SND spare the sternocleidomastoid muscle (SCM), the internal jugular vein (IJV), and the spinal accessory nerve (SAN). When an SND is associated with the resection of 1 or more nonlymphatic structures, it should be termed ESND. All additional nonlymphatic structure(s) removed should be identified in parentheses. The proposal to subclassify SND not only in accord with the resected lymph node levels but also upon the nonlymphatic structures removed may be of some help to avoid potential misinterpretation. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Designing biomarker studies for head and neck cancer

Although there is ample literature reporting on the identification of molecular biomarkers for head and neck squamous cell carcinoma, none is currently recommended for routine clinical use. A major reason for this lack of progress is the difficulty in designing studies in head and neck cancer to clearly establish the clinical utility of biomarkers. Consequently, biomarker studies frequently stall at the initial discovery phase. In this article, we focus on biomarkers for use in clinical management, including selection of therapy. Using several contemporary examples, we identify some of the common deficiencies in study design that hinder success in biomarker development for this disease area, and we suggest some potential solutions. The purpose of this article is to provide guidance that can assist investigators to more efficiently move promising biomarkers in head and neck cancer from discovery to clinical practice. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1069–1075, 2014