The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Organizational guidance for the care of patients with head-and-neck cancer in Ontario.

Background: At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer. Methods: This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline The Management of Head and Neck Cancer in Ontario. The guideline development methods included an updated literature search, internal review by content and methodology experts, and external review by relevant health care providers and potential users. Results: To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the minimum requirements to maintain a head-and-neck disease site program. Recommendations are made about the membership of core and extended provider teams, minimum skill sets and experience of practitioners, cancer centre-specific and practitioner-specific volumes, multidisciplinary care requirements, and unique infrastructure demands. Conclusions: The recommendations contained in this document offer guidance for clinicians and institutions providing care for patients with head-and-neck cancer in Ontario, and for policymakers and other stakeholders involved in the delivery of health care services for head-and-neck cancer.

Intraoperative cone-beam CT spatial priors for diffuse optical fluorescence tomography.

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization ('soft spatial priors'). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and <20% for no priors and spatial priors, respectively. Similar results were observed with the ICG target embedded in ex vivo porcine loin, with errors of 52% and 12%, respectively. A proof-of-principal animal study was performed in a VX2-tumor in vivo rabbit model using liposomal nanoparticles co-encapsulating contrast for CT (iohexol) and fluorescence (ICG) imaging. Fusion of CBCT and FT reconstructions demonstrated concurrent anatomical and functional delineations of contrast enhancement around the periphery of the buccal tumor. These developments motivate future clinical translation of the FT system into an ongoing CBCT-guided head and neck surgery trial.

Navigated non-contact fluorescence tomography.

A non-contact approach for diffuse optical tomography (DOT) has been developed for on-demand image updates using surgical navigation technology. A stereoscopic optical tracker provides real-time localization of reflective spheres mounted to a laser diode and near-infrared camera. Standard camera calibration is combined with tracking data to determine the intrinsic camera parameters (focal length, principal point and non-linear lens distortion) and the tracker-to-camera transform. Tracker-to-laser calibration is performed using images of laser beam intersection with a tracked calibration surface. Source and detector positions for a finite-element DOT implementation are projected onto the boundary elements of the tissue mesh by finding ray-triangle intersections. A multi-stage model converts camera counts to surface flux by accounting for lens aperture settings, fluorescence filter transmittance, photodetector quantum efficiency, photon energy, exposure time, readout offset and camera gain. The image-guidance framework was applied to an in-house optical tomography system configured for indocyanine green (ICG) fluorescence. Mean target registration errors for camera and laser calibration were less than 1 mm. Surface flux measurements of total reflectance and fluorescence in Intralipid-based fluorescence phantoms (0-2 µg ml-1) had mean errors of 3.1% and 4.4%, respectively, relative to diffusion theory predictions. Spatially-resolved reflectance measurements in a calibrated optical phantom agreed with theory for radial distances up to 25 mm from the laser source. Inverse fluorescence reconstructions of a sub-surface fluorescence target confirmed the localization accuracy (average target centroid error of 0.44 mm). This translational research system is under investigation for clinical applications in head and neck surgery, including oral cavity tumor resection, lymph node mapping and free-flap perforator assessment.

Radiologic-Pathologic Correlation of Tumor Thickness and Its Prognostic Importance in Squamous Cell Carcinoma of the Oral Cavity: Implications for the Eighth Edition Tumor, Node, Metastasis Classification.

BACKGROUND AND PURPOSE: Addressing the performance of an imaging-based parameter compared to a "gold standard" pathologic measurement is essential to achieve accurate clinical T-classification. Our aim was to determine the radiologic-pathologic tumor thickness correlation and its prognostic value in oral squamous cell carcinoma. MATERIALS AND METHODS: All pathologic T1-T3 (seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer) oral squamous cell carcinomas diagnosed between 2010 and 2015 were reviewed. Radiologic tumor thickness was measured on preoperative CT or MR imaging blinded to pathology. The radiologic-pathologic tumor thickness correlation was calculated. The impact of the imaging-to-surgery time interval and imaging technique on the correlation was explored. Intra-/interrater reliability on radiologic tumor thickness was calculated. The correlation of radiologic-versus-pathologic tumor thickness and its performance as the seventh edition T-category modifier was evaluated. Multivariable analysis assessed the prognostic value of the radiologic tumor thickness for overall survival adjusted for age, seventh edition T-category, and performance status. RESULTS: For 354 consecutive patients, the radiologic-pathologic tumor thickness correlation was similar for the image-to-surgery interval of ≤4.0 weeks (ρ = 0.76) versus 4-8 weeks (ρ = 0.80) but lower in those with more than an 8-week interval (ρ = 0.62). CT and MR imaging had similar correlations (0.76 and 0.80). Intrarater and interrater reliability was excellent (0.88 and 0.84). Excluding 19 cases with an imaging-to-surgery interval of >8 weeks, 335 patients were eligible for further analysis. The radiologic-pathologic tumor thickness correlation was 0.78. The accuracy for upstaging the T-classification based on radiologic tumor thickness was 83% for pathologic T1 and 74% for pathologic T2 tumors. Multivariable analysis confirmed the prognostic value of radiologic tumor thickness (hazard ratio = 1.5, P = .02) for overall survival. CONCLUSIONS: This study demonstrates a good radiologic-pathologic tumor thickness correlation. Intrarater and interrater reliability for radiologic tumor thickness was excellent. Radiologically thicker tumor was predictive of inferior survival.

Emergency department visits and unplanned hospitalizations in the treatment period for head and neck cancer patients treated with curative intent: A population-based analysis.

BACKGROUND: Mucosal head and neck squamous cell cancers are often managed with multimodality treatment which can be associated with significant toxicity. The objective of this study was to assess emergency department visits and unplanned hospitalizations for these patients during and immediately after their treatment. METHODS: A cohort of patients treated for head and neck squamous cell carcinoma was developed using administrative data. Emergency department visits and hospitalizations in the 90-day post-treatment period was determined. If a second treatment was initiated prior to the completion of 90 days, the attributable risk period was changed to the second treatment. RESULTS: Cohort of 3898 patients (1312 larynx/hypopharynx; 2586 oral cavity/oropharynx) from 2008 to 2012. The number of unplanned hospitalizations or ED visits (per 100 patient days) were 0.69 for surgery, 0.78 for surgery followed by concurrent chemoradiotherapy (CCRT), 0.55 for surgery followed by radiotherapy, 0.86 for CCRT, and 0.50 for radiation. Patients receiving CCRT had a statistically higher likelihood of treatment period events. The larynx/hypopharynx cancer subsite, higher comorbidity and more advanced stage of disease were all independent predictors of events. CONCLUSIONS: Patients undergoing treatment for head and neck cancer have significant unplanned hospitalizations and visits to the emergency department in the treatment period. Rates are higher in patients receiving CCRT. Quality improvement interventions should be used to improve these rates.

Symptom appraisal, help seeking, and lay consultancy for symptoms of head and neck cancer.

OBJECTIVE: Early diagnosis is important in head and neck cancer (HNC) patients to maximize the effectiveness of the treatments and minimize the debilitation associated with both the cancer and the invasive treatments of advanced disease. Many patients present with advanced disease, and there is little understanding as to why. This study investigated patients' symptom appraisal, help seeking, and lay consultancy up to the time they first went to see a health care professional (HCP). METHODS: We interviewed 83 patients diagnosed with HNC. The study design was cross sectional and consisted of structured telephone interviews and a medical chart review. We gathered information on the participant's personal reactions to their symptoms, characteristics of their social network, and the feedback they received. RESULTS: We found that 18% of the participants thought that their symptoms were urgent enough to warrant further investigation. Participants rarely (6%) attributed their symptoms to cancer. Eighty-nine percent reported that they were unaware of the early warning signs and symptoms of HNC. Fifty-seven percent of the participants disclosed their symptoms to at least one lay consultant before seeking help from an HCP. The lay consultants were usually their spouse (77%), and the most common advice they offered was to see a doctor (76%). Lastly, 81% of the participants report that their spouse influenced their decision to see an HCP. CONCLUSIONS: The results of this study suggest that patients frequently believe that their symptoms were nonurgent and that their lay consultants influence their decision to seek help from an HCP.

Fluctuating asymmetry in dental and mandibular nonmetric traits as evidence for childcare sex bias in 19th/20th century Portugal.

Fluctuating asymmetry, often considered a measure of developmental instability, was studied in the dental morphological traits of 600 individuals from among the poorest sectors of society in 19th-20th century Portugal. The aims are to identify and interpret any differences between: (1) males and females, and (2) patterns of distribution among teeth with different odontogenic timings, to assess if any sex bias existed in childcare. Dental and mandibular morphological traits were recorded using the Arizona State University Dental Anthropology System. z-Ratios were used to compare summed absolute fluctuating asymmetry frequencies between sexes and age groups. Results from rank correlation coefficients ruled out directional asymmetry and antisymmetry, based on positive (>0.2) bilateral association of traits in larger samples. Sex differences were significant (z-ratio=3.128; p=0.0018), while age differences were not (z-ratio=-0.644; p=0.5196). Teeth forming after infancy tended to be more asymmetric in females. Potential reasons for the sex difference include: (1) greater female susceptibility to developmental instability, (2) greater male childhood mortality that yields lower fluctuating asymmetry in surviving males, and/or (3) cultural bias favoring male access to resources. Results suggest the latter hypothesis is most likely, as fluctuating asymmetry is enhanced during childhood, perhaps coinciding with gender role definitions. There seems to be no association between asymmetry and early mortality in males. A lack of parallels in prior research renders differential sex reaction to environmental stress dubious. This population may have favored male children in their access to appropriate conditions for development.

Correlation between clinical and MRI assessment of depth of invasion in oral tongue squamous cell carcinoma.

BACKGROUND: Neck metastasis is the most important prognostic factor in oral cavity squamous cell carcinomas (SCC). Apart from the T- stage, depth of invasion has been used as a highly predictable factor for microscopic neck metastasis, despite the controversy on the exact depth cut off point. Depth of invasion can be determined clinically and radio logically. However, there is no standard tool to determine depth of invasion preoperatively. Although MRI is used widely to stage the head and neck disease, its utility in depth evaluation has not formally been assessed. OBJECTIVE: To compare preoperative clinical and radiological depth evaluation in oral tongue SCC using the standard pathological depth. To compare clinical and radiological accuracy between superficial (<5 mm) vs. deep invaded tumor (≥5 mm) METHODS: This prospective study used consecutive biopsy-proven oral tongue invasive SCC that presented to the University health network (UHN), Toronto. Clinical examination, radiological scan and appropriate staging were determined preoperatively. Standard pathology reports postoperatively were reviewed to determine the depth of invasion from the tumor specimen. RESULTS: 72 tumour samples were available for analysis and 53 patients were included. For all tumors, both clinical depth (r = 0.779; p < 0.001) and radiographic depth (r =0.907; p <0.001) correlated well with pathological depth, with radiographic depth correlating slightly better. Clinical depth also correlated well with radiographic depth (r = 0.731; p < 0.001). By contrast, for superficial tumors (less than 5 mm on pathological measurement) neither clinical (r = 0.333, p = 0.34) nor radiographic examination (r = - 0.211; p = 0.56) correlated with pathological depth of invasion. CONCLUSION: This is the first study evaluating the clinical assessment of tumor thickness in comparison to radiographic interpretation in oral cavity cancer. There are strong correlations between pathological, radiological, and clinical measurements in deep tumors (≥5 mm). In superficial tumors (<5 mm), clinical and radiological examination had low correlation with pathological thickness.

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands.

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

The optimal organization of gynecologic oncology services: a systematic review.

BACKGROUND: A system-level organizational guideline for gynecologic oncology was identified by a provincial cancer agency as a key priority based on input from stakeholders, data showing more limited availability of multidisciplinary or specialist care in lower-volume than in higher-volume hospitals in the relevant jurisdiction, and variable rates of staging for ovarian and endometrial cancer patients. METHODS: A systematic review assessed the relationship of the organization of gynecologic oncology services with patient survival and surgical outcomes. The electronic databases medline and embase (ovid: 1996 through 9 January 2015) were searched using terms related to gynecologic malignancies combined with organization of services, patterns of care, and various facility and physician characteristics. Outcomes of interest included overall or disease-specific survival, short-term survival, adequate staging, and degree of cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by hospital or physician type, and rate of discrepancy in initial diagnoses and intraoperative consultation between non-specialist pathologists and gyne-oncology-specialist pathologists. RESULTS: One systematic review and sixteen additional primary studies met the inclusion criteria. The evidence base as a whole was judged to be of lower quality; however, a trend toward improved outcomes with centralization of gynecologic oncology was found, particularly with respect to the gynecologic oncology care of patients with advanced-stage ovarian cancer. CONCLUSIONS: Improvements in outcomes with centralization of gynecologic oncology services can be attributed to a number of factors, including access to specialist care and multidisciplinary team management. Findings of this systematic review should be used with caution because of the limitations of the evidence base; however, an expert consensus process made it possible to create recommendations for implementation.

Adherence to and uptake of clinical practice guidelines: lessons learned from a clinical practice guideline on chemotherapy concomitant with radiotherapy in head-and-neck cancer.

BACKGROUND: Clinical practice guidelines (cpgs) are systematically developed statements designed to assist practitioners and patients in making decisions about appropriate heath care interventions. Clinical practice guidelines are expensive and time-consuming to create. A cpg on concurrent chemotherapy with radiation therapy (ccrt) was developed in Ontario at a time when treatment approaches for head-and-neck cancer were changing significantly. METHODS: An assessment of treatments and outcomes based on electronic and chart data obtained from a population-based study of 571 patients with oropharynx cancer treated in Ontario (2003-2004) was combined with a review of relevant knowledge transfer (publications and presentations at major meetings) to understand variation in adherence to a cpg. RESULTS: In 9 Ontario cancer treatment centres, ccrt was used for 55% of all patients with oropharyngeal cancer; however, at the centres individually, that proportion ranged from 82% to 39%. Furthermore, there was no agreement on the chemotherapy regimen: 2-4 years later (a period during which newer regimens were emerging), only 4 of 9 centres were following the guideline for most patients. When outcomes of treated patients were compared for centres with "higher" and "lower" use of ccrt, no difference in survival was observed (p = 0.64). CONCLUSIONS: At a time of treatment evolution, the new guideline was controversial, and there are many reasons for the mixed adherence. An estimation of adherence should be included during both development and review of guidelines.

Long-term seafloor monitoring at an open ocean aquaculture site in the western Gulf of Maine, USA: development of an adaptive protocol.

The seafloor at an open ocean finfish aquaculture facility in the western Gulf of Maine, USA was monitored from 1999 to 2008 by sampling sites inside a predicted impact area modeled by oceanographic conditions and fecal and food settling characteristics, and nearby reference sites. Univariate and multivariate analyses of benthic community measures from box core samples indicated minimal or no significant differences between impact and reference areas. These findings resulted in development of an adaptive monitoring protocol involving initial low-cost methods that required more intensive and costly efforts only when negative impacts were initially indicated. The continued growth of marine aquaculture is dependent on further development of farming methods that minimize negative environmental impacts, as well as effective monitoring protocols. Adaptive monitoring protocols, such as the one described herein, coupled with mathematical modeling approaches, have the potential to provide effective protection of the environment while minimize monitoring effort and costs.

Illuminating the Nubian 'Dark Age': a bioarchaeological analysis of dental non-metric traits during the Napatan Period.

The origins of one of the most powerful sociopolitical entities of the Nile Valley, the Napatan State (850-650BCE), are debated. Some scholars have suggested local development of this influential Nubian State, while others propose foreign involvement. This study uses a bioarchaeological approach to examine the biological affinity of these Ancient Nubians. The focal site of this research, Tombos, is one of few non-central Napatan Period sites that have been excavated and can, therefore, shed light on the broader Napatan populace. Dental non-metric trait frequencies were examined in the Tombos sample as well as in 12 comparative samples to elucidate the biological affinities of these populations. Analyses indicate that Tombos dental non-metric trait frequencies were not significantly different from the majority of Egyptian and Nubian samples examined here. Therefore, we propose that gene flow, encouraged by long-term coexistence and intermarriage in Nubia, created an Egyptian/Nubian transcultural environment. These findings suggest the Napatan population at Tombos included descendants of Egyptians and Nubians. The Napatan Tombos sample was found to significantly differ from the latter Kushite and Meroitic samples; however, these samples are so temporally removed from the Napatan Period, we suspect subsequent episodes of population movement may have contributed to this variation.

Assessing change in diet and biological affinity between the 4th and 3rd millennia cal BCE in the Portuguese Estremadura: a preliminary dental comparison of Feteira II and Bolores.

Although the social and political changes accompanying the transition from the Neolithic through Copper Age, between the 4th and 3rd millennia cal BCE, in southwestern Iberia are reasonably well understood, much less is known about whether population movements and dietary changes accompanied these transformations. To address this question, human dental remains from the Middle through Late Neolithic site of Feteira II (3600-2900 cal BCE) and the Late Neolithic site of Bolores (2800-2600 cal BCE) in the Portuguese Estremadura were used to examine diet (microwear) and affinity (dental non-metrics). Microwear features were not found to be significantly different between Feteira II and Bolores, suggesting that the emergence of social complexity during this period did not result in large-scale changes in subsistence practices during the period of use at these sites. Using the Arizona State University Dental Anthropology System and supporting statistics, no significant difference between the samples from Feteira II and Bolores was observed, suggesting that no population replacement occurred between the Middle Neolithic and Late Neolithic/Copper Age. However, at Bolores there is some indication that there may have been demographic exchanges between southern Iberian and North African populations during the Late Neolithic/Copper Age.

Within-population diversity of koala Chlamydophila pecorum at ompA VD1-VD3 and the ORF663 hypothetical gene.

Infection of koalas by Chlamydophila pecorum is very common and causes significant morbidity, infertility and mortality. Fundamental to management of the disease is an understanding of the importance of multi-serotype infection or pathogen virulence in pathogenesis; these may need consideration in plans involving koala movement, vaccination, or disease risk assessment. Here we describe diversity of ompA VD1-3, and ORF663 hypothetical gene tandem repeat regions, in a single population of koalas with diverse disease outcomes. We PCR amplified and sequenced 72 partial ompA segments and amplified 25 tandem repeat segments (ORF663 hypothetical gene) from C. pecorum obtained from 62 koalas. Although several ompA genotypes were identified nationally, only one ompA genotype existed within the population studied, indicating that severe chlamydial disease occurs commonly in free-ranging koalas in the absence of infection by multiple MOMP serotypes of C. pecorum. In contrast, variation in tandem repeats within the ORF663 hypothetical gene was very high, approaching the entire range reported for pathogenic and non-pathogenic C. pecorum of European ruminants; providing an impetus for further investigation of this as a potential virulence trait.

Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors.

BACKGROUND: Tobacco smoking and high alcohol consumption are considered major risk factors of oral tongue squamous cell carcinoma. This study compared disease outcome between patients with and without known risk factors. METHODS: Patients with oral tongue squamous cell carcinoma treated at two major medical centers from 1994 to 2008 were identified by cancer registry search. The medical files were reviewed for background-and-disease-related data, risk factors, and outcome. RESULTS: The study sample consisted of 291 patients: 175 had a history of heavy tobacco smoking and alcohol abuse and 116 did not. Comparison of the patients without risk factors between the two centers yielded no differences in background features. Men accounted for 74% of the total patients with risk factors and comprised 77% of the risk-factor group. The risk-factor group was characterized by a significantly higher mean tumor grade (p=0.0001) and greater tumor depth of invasion (p=0.022) than the non-risk-factor group. The 5-year local and regional control rates were 85.3% and 74%, respectively, with no significant difference between the groups. The 5-year overall survival rate was 68% in the risk-factor group and 64% in the non-risk-factor group (p=NS). Separate analysis of patients aged <40 years at diagnosis revealed a worse overall (p=0.015) and disease-free survival (p=0.038) in those without risk factors. CONCLUSIONS: The outcome of oral tongue carcinoma is similar in patients with and without risk factors. The worse prognosis in younger patients (<40 years) without risk factors suggests that the pathogenesis in these cases involves factors other than smoking and alcohol.

Laryngeal cancer treatment and survival differences across regional cancer centres in Ontario, Canada.

AIMS: We conducted a population-based study of practice patterns and outcome across the regional cancer centres providing care to patients with laryngeal cancer in the Province of Ontario, Canada. MATERIALS AND METHODS: : This was a retrospective cohort study of 1547 patients with cancers of the glottic or supraglottic larynx diagnosed between 1982 and 1995. Data were collected via chart review, including: patient and disease characteristics, treatment, waiting times and treatment volumes. Vital status was obtained from the Ontario Cancer Registry. Variations across the nine regional cancer centres are described and their effect on outcome explored. All analyses were stratified by stage I and II separately from stage III and IV. RESULTS: Treatments differed across centres (P<0.0001); for instance, in the stage I and II group, use of a daily dose of >2.54Gy varied from 0 to 87.6% and in the stage III and IV group, total laryngectomy rates varied from a low of 6% to a high of 53%. The percentage of patients waiting more than 6 weeks from diagnosis to first treatment varied from 17 to 49% (P<0.0001). Multivariate analysis revealed cause-specific survival differences that were not explained by control for case mix, treatment or waiting times. Differences ranged from an 82% risk reduction in one centre compared with the reference (stage I and II group, P=0.008) to a 153% increase in risk (stage III and IV group, P=0.02). Centre case volumes were not associated with cause-specific survival. CONCLUSIONS: This study quantifies the degree of variation that can occur in the treatment and outcome of people with cancer. We cannot properly assess whether care delivery is of high quality until we have a better understanding of the factors that drive such variations.

Dental affinities of the C-group inhabitants of Hierakonpolis, Egypt: Nubian, Egyptian, or both?

By c. 2050 BC a small community of C-Group Nubians was present deep within Egyptian territory at the city of Hierakonpolis. Their descendants stayed for the next 400 years. Today, the site of Hierakonpolis, 113 km north of Aswan, is known for its Egyptian deposits; however, it also contains a C-Group cemetery, which documents the northernmost occurrence of this culture. Sixty skeletons were excavated. Tombs feature Nubian architecture and goods, including leather garments, although the use of Egyptian mortuary practices and artifacts increased through time. Dates range from the early 11th Dynasty into the Second Intermediate period. During this time the Egyptian empire occupied Lower Nubia, and their state ideology vilified Nubians. Yet, at least in death, the C-Group inhabitants of Hierakonpolis proudly displayed their cultural heritage. Beyond discerning the reason(s) for their presence at the site (e.g., mercenaries, leather-workers, entertainers?), the focus of this report is to estimate their biological affinity. Were they akin to other Nubians, Egyptians, or both? And, was increasing 'Egyptianization' evident in the mortuary ritual accompanied by concomitant genetic influence? To address these queries, up to 36 dental morphological traits in the recovered individuals were compared to those in 26 regional comparative samples. The most influential traits were identified and phenetic affinities were calculated using the mean measure of divergence and other multivariate analyses. Assuming phenetic similarity provides an estimate of genetic relatedness, these affinities suggest the individuals comprising the C-Group sample were, and remained Nubian during their tenure at Hierakonpolis.

Demons deformable registration for CBCT-guided procedures in the head and neck: convergence and accuracy.

PURPOSE: The accuracy and convergence behavior of a variant of the Demons deformable registration algorithm were investigated for use in cone-beam CT (CBCT)-guided procedures of the head and neck. Online use of deformable registration for guidance of therapeutic procedures such as image-guided surgery or radiation therapy places trade-offs on accuracy and computational expense. This work describes a convergence criterion for Demons registration developed to balance these demands; the accuracy of a multiscale Demons implementation using this convergence criterion is quantified in CBCT images of the head and neck. METHODS: Using an open-source "symmetric" Demons registration algorithm, a convergence criterion based on the change in the deformation field between iterations was developed to advance among multiple levels of a multiscale image pyramid in a manner that optimized accuracy and computation time. The convergence criterion was optimized in cadaver studies involving CBCT images acquired using a surgical C-arm prototype modified for 3D intraoperative imaging. CBCT-to-CBCT registration was performed and accuracy was quantified in terms of the normalized cross-correlation (NCC) and target registration error (TRE). The accuracy and robustness of the algorithm were then tested in clinical CBCT images of ten patients undergoing radiation therapy of the head and neck. RESULTS: The cadaver model allowed optimization of the convergence factor and initial measurements of registration accuracy: Demons registration exhibited TRE=(0.8+/-0.3) mm and NCC =0.99 in the cadaveric head compared to TRE=(2.6+/-1.0) mm and NCC=0.93 with rigid registration. Similarly for the patient data, Demons registration gave mean TRE=(1.6+/-0.9) mm compared to rigid registration TRE=(3.6+/-1.9) mm, suggesting registration accuracy at or near the voxel size of the patient images (1 x 1 x 2 mm3). The multiscale implementation based on optimal convergence criteria completed registration in 52 s for the cadaveric head and in an average time of 270 s for the larger FOV patient images. CONCLUSIONS: Appropriate selection of convergence and multiscale parameters in Demons registration was shown to reduce computational expense without sacrificing registration performance. For intraoperative CBCT imaging with deformable registration, the ability to perform accurate registration within the stringent time requirements of the operating environment could offer a useful clinical tool allowing integration of preoperative information while accurately reflecting changes in the patient anatomy. Similarly for CBCT-guided radiation therapy, fast accurate deformable registration could further augment high-precision treatment strategies.