Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Web-Based Tool for Standardized Reporting of Thyroid Ultrasound Studies.

OBJECTIVE: Our objective was to create a user-friendly synoptically driven web-based tool for radiologists to report thyroid ultrasound studies and thereby improve the quality, completeness, and recommendations of reports. CONCLUSION: The tool, developed using JavaScript and PHP (hypertext preprocessor), provides radiologists with a way to generate complete thyroid ultrasound reports and automatically categorize thyroid nodules of varying suspicion. Future work will focus on integration with the radiology information system for seamless reporting and the development of a prospective database.

Incomplete Thyroid Ultrasound Reports for Patients With Thyroid Nodules: Implications Regarding Risk Assessment and Management.

OBJECTIVE: The purpose of this study was to determine the completeness of thyroid ultrasound (US) reports, assess for differences in report interpretation by clinicians, and evaluate for implications in patient care. MATERIALS AND METHODS: We retrospectively reviewed thyroid US examinations performed between January and June 2013 in Nova Scotia, Canada. Baseline examinations that identified a nodule were evaluated for 10 reporting elements. Reports that lacked a comment regarding malignancy risk or a recommendation for biopsy were considered unclassified and were graded by three clinical specialists in accordance with the 2015 American Thyroid Association management guidelines. Interrater agreement was assessed using the Cohen kappa statistic. A radiologist reviewed the images of unclassified nodules, and on the basis of radiologic grading, biopsy rates and pathologic findings were compared between nodules that did and did not warrant biopsy. RESULTS: Of 971 first-time thyroid US studies, 478 detected a nodule. The number of reports lacking a comment on the 10 elements ranged from 154 to 433 (32-91%). A total of 222 nodules (46%) were unclassified, and agreement in assigned grading by the clinical specialists was very poor (κ = 0.07; p < 0.05). According to radiologist grading, only 57 of 127 biopsies were performed on nodules that warranted biopsy, and 16 of 95 biopsies were performed unnecessarily. On the basis of the three clinical specialists' interpretation, 10, 31, and 33 reports were considered too incomplete to assign a grade; 40, 10, and four biopsies would have been unnecessarily ordered; and zero, three, and four cancers would have been missed. CONCLUSION: There is widespread underreporting of established elements in thyroid US reports, and this causes confusion and discrepancy among clinical specialists regarding the risk of malignancy and the need for biopsy.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Head and Neck Radiation Therapy Patterns of Practice Variability Identified as a Challenge to Real-World Big Data: Results From the Learning from Analysis of Multicentre Big Data Aggregation (LAMBDA) Consortium.

Purpose: Outside of randomized clinical trials, it is difficult to develop clinically relevant evidence-based recommendations for radiation therapy (RT) practice guidelines owing to lack of comprehensive real-world data. To address this knowledge gap, we formed the Learning from Analysis of Multicenter Big Data Aggregation consortium to cooperatively implement RT data standardization, develop software solutions for data analysis, and recommend clinical practice change based on real-world data analyzed. The first phase of this "Big Data" study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs) that would undermine subsequent use of large-scale, electronically aggregated data to characterize associations with outcomes. Evidence from this study was used as the basis for practical recommendations to improve data quality. Methods and Materials: Dosimetric details of patients with head and neck cancer treated with radiation therapy between 2014 and 2019 were analyzed. Institutional patterns of practice were characterized, including structure nomenclature, volumes, and frequency of contouring. Dose volume histogram (DVH) distributions were characterized and compared with institutional constraints and literature values. Results: Plans for 4664 patients treated to a mean plan dose of 64.4 ± 13.2 Gy in 32 ± 4 fractions were aggregated. Before implementation of TG-263 guidelines in each institution, there was variability in OAR nomenclature across institutions and structures. With evidence from this study, we identified a targeted and practical set of recommendations aimed at improving the quality of real-world data. Conclusions: Quantifying similarities and differences among institutions for OAR structures and DVH metrics is the launching point for next steps to investigate potential relationships between DVH parameters and patient outcomes.

Prevalence of atrial fibrillation in patients taking TSH suppression therapy for management of thyroid cancer.

BACKGROUND: Suppression of thyroid stimulating hormone (TSH) below the normal range with administration of L-thyroxine has been shown to improve survival in patients treated for thyroid cancer (TC). Although most TC patients require long-term TSH suppression therapy, the effect of this treatment on cardiac rhythm remains unknown. A cross-sectional study was conducted to determine the prevalence of atrial fibrillation (AF) in TC patients on TSH suppressive therapy. METHODS: All TC patients seen between June 2009 and March 2010 through a multidisciplinary thyroid oncology clinic, Halifax, Nova Scotia, Canada, for whom TSH suppressive therapy had previously been recommended, were recruited into the study. Each patient underwent an electrocardiogram and filled out a questionnaire relevant to causes, signs/symptoms of AF and/or its complications. The prevalence of AF in this population then was compared against the published prevalence of AF in general populations. RESULTS: A total of 351 patients were seen in the thyroid clinic of which 136 patients met the inclusion criteria for the study. The mean age was 52 years, 85% were female, and mean follow-up duration prior to recruitment was 11 years. The mean TSH was 0.17 mIU/L (Normal: 0.35 - 5.5 mIU/L). There were 14 patients found to have AF (two patients had long-standing persistent AF and 12 patients had paroxysmal AF). The mean ages of patients with and without AF were 61.6 years and 51.4 years, respectively (P = 0.01). Prevalence of AF in the study group was 10.3%; the rate of AF in the TC patients aged 60 years and over (17.5%) was higher than the rate of AF in published data in people 60 years and over (P < 0.001). AF was diagnosed after the initiation of the TSH suppression therapy in all except one patient. CONCLUSION: TSH suppression in thyroid cancer is associated with a high prevalence of AF, particularly in older individuals.

Canadian consensus statement on the management of radioactive iodine-resistant differentiated thyroid cancer.

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

Patient and tumor factors contributing to distant metastasis in well-differentiated thyroid cancer: a retrospective cohort study.

BACKGROUND: Distant metastasis in thyroid cancer significantly reduces survival in patients with well-differentiated thyroid carcinoma (WDTC). There is limited information available to clinicians regarding pathological features that confer a higher risk of distant metastasis (DM). This study aimed to identify patient and tumor factors that were associated with the development of DM over time in patients with WDTC. METHODS: A retrospective cohort analysis of patients with WDTC (n = 584) at our institution was performed between 2007 and 2017. A total of 39 patients with DM and 529 patients with no DM (NDM) were included. Patient demographics, tumor characteristics and patient survival were compared between the DM and NDM groups using a univariate analysis. Multivariate Cox-proportional hazards model was used to evaluate the risk of developing distant metastasis over time. Kaplan-Meier analysis was used to compare survival between the DM and NDM groups. RESULTS: Distant metastasis had a substantial impact on disease-specific survival (DSS) at 5 and 10-years in the DM group; 71.0% (SE 8.4%) and 46.9% (SE 11.6%) respectively, compared to 100% survival in the NDM group (p < 0.001). The DM group had significantly higher proportions of males, lymphovascular invasion (LVI), nodal metastasis (NM), large tumor size (TS), extrathyroidal extension (ETE), positive resection margins, multifocality, follicular thyroid cancer (FTC), tall cell variant of papillary thyroid cancer (PTC), and Hurthle cell carcinoma (HCC), when compared to the NDM group (p < 0.05). A TS ≥ 2 cm (Hazard Ratio (HR) 1.370), NM (HR 3.806) and FTC (HR 7.068) were associated with a significantly increased hazard of developing distant metastasis in patients with WDTC. CONCLUSIONS: TS ≥ 2 cm, NM and FTC are associated with a significantly increased propensity for developing DM in our cohort of WDTC patients.

Risk for Thyroid Cancer Recurrence Is Higher in Men Than in Women Independent of Disease Stage at Presentation.

Background: Well-differentiated thyroid cancer (DTC) presents at a more advanced stage in men than in women, and the mortality in men is higher than that in women. However, it is not clear whether DTC recurrence is affected by sex independent of stage at presentation. The objective of the present study was to assess if male sex is an independent risk factor for recurrence of DTC. Methods: The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe patterns of care for thyroid cancer. We included patients from the CANNECT registry with DTC diagnosed at age 18 or older between 2000 and 2010. We compared men and women with respect to presentation, management, and recurrence risk, stratified for American Joint Committee on Cancer (AJCC) stage. Results: We included 2595 patients, 2067 (79.7%) women and 528 (20.3%) men. Men presented with more advanced AJCC stage (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), and M stage (p = 0.002) There was no difference in follow-up duration between women (7.7 ± 4.0 [mean ± standard deviation] years) and men (7.7 ± 4.0 years, p = 0.985). Overall recurrence was 2.2% (n = 46) for women and 8.5% (n = 45) for men (p < 0.001). In multivariate analysis adjusted for AJCC stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.72 [95% confidence interval [CI] 1.78-4.20]; p < 0.001). In multivariate analysis adjusted for tumor-node-metastasis (TNM) stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.31 [CI 1.48-3.60]; p < 0.001). Conclusions: Our study confirms that the risk for recurrence of DTC is higher in men than in women. Although men tend to present with more advanced-stage disease, the difference in recurrence risk persists when adjusted for stage of presentation. It needs to be determined whether sex should influence follow-up intensity and/or duration.

Primary versus Tertiary Care Follow-Up of Low-Risk Differentiated Thyroid Cancer: Real-World Comparison of Outcomes and Costs for Patients and Health Care Systems.

BACKGROUND: An unprecedented rise in the prevalence of low-risk well-differentiated thyroid cancer (TC) has been reported in several countries, which is partly due to an increased utility of sensitive imaging techniques. The outcome of these cancers has generally remained excellent and the overall 5-year survival is almost 100%. However, the extended follow-up strategy for these patients remains unclear and while the initial management is done in specialist centres some experts opt to follow them on a long-term basis while others discharge them to primary care after the initial management. The effectiveness of one strategy versus the other has not been studied. METHODS: We conducted a real-world comparison to assess the outcome of low-risk TC (AJCC stage I) with undetectable thyroglobulin (TG) 2 years after radio-iodine (I-131) therapy. The outcome from Halifax (NS, Canada) and London (ON, Canada), where all TC patients are routinely followed by the tertiary care team, was compared with that from Edmonton (AB, Canada), where patients are routinely discharged to primary care. RESULTS: All patients were diagnosed between January 1, 2006, and December 31, 2011. The mean follow-up in primary care after discharge was 62.2 months and in tertiary care it was 64.6 months (p = 0.43). Rates of recurrence were similar in both groups, i.e., 1.1% in primary care and 1.3% in tertiary care (p = 0.69). Ultrasound surveillance was conducted in 56.5% of the patients in primary care and 52.6% of the tertiary care group (p = 0.26). The rate of annual unstimulated TG testing per patient was 0.58 (range 0-14) in primary care and 0.96 (range 0-6) in tertiary care (p = 0.06). More patients in primary care (86%) than in tertiary care (29.9%) consistently had thyroid-stimulating hormone levels within the target range (p < 0.001). The mean healthcare cost, based on a single follow-up visit with a blood test and ultrasound in the primary care group was CAD 118.01 and in the tertiary care group it was CAD 164.12. CONCLUSION: Our study shows that extended follow-up of low-risk TC patients is perfectly feasible in primary care and provides significant economic benefit for the healthcare system.

Use of radioiodine-131 scan to measure influence of surgical discipline, practice, and volume on residual thyroid tissue after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: Our study's purpose is to determine the influence of surgical discipline, surgeon site, and volume on remnant thyroid tissue visualized on radioactive iodine-131 (I-131) scans after total thyroidectomy and I-131 ablation in patients with well-differentiated thyroid carcinomas. METHODS: We retrospectively reviewed all cases of patients who received I-131 therapeutic ablation and postablation radioactive I-131 scans at our center after thyroidectomy to calculate the fraction of administered dose multiplied by 1000 (UDR1000). RESULTS: The remnant thyroid tissue (ie, the UDR1000), between academic and community surgeons was 0.471 (±0.705) and 1.190 (±2.487), respectively (P = .001). The UDR1000 between otolaryngology-head and neck surgery and general surgery was 0.654 (±1.575) and 1.043 (±1.625), respectively (P = .159). The UDR1000 partitioned by patient frequencies of <10, 10 to 19, and ≥20 patients yielded 1.255 (±2.554), 0.926 (±2.084), and 0.467 (±0.721), respectively (P = .003). CONCLUSION: Our study found statistically significant differences in residual thyroid tissue visualized on radioactive I-131 scans based on surgeon parameters.

Spatial and dosimetric variability of organs at risk in head-and-neck intensity-modulated radiotherapy.

PURPOSE: The accuracy of intensity-modulated radiotherapy (IMRT) delivery may be compromised by random spatial error and systematic anatomic changes during the treatment course. We present quantitative measurements of the spatial variability of head-and-neck organs-at-risk and demonstrate the resultant dosimetric effects. METHODS AND MATERIALS: Fifteen consecutive patients were imaged weekly using computed tomography during the treatment course. Three-dimensional displacements were calculated for the superior and inferior brainstem; C1, C6, and T2 spinal cord; as well as the lateral and medial aspects of the parotid glands. The data were analyzed to show distributions of spatial error and to track temporal changes. The treatment plan was recalculated on all computed tomography sets, and the dosimetric error was quantified in terms of the maximal dose difference (brainstem and spinal cord) or the mean dose difference and the volume receiving 26 Gy (parotid glands). RESULTS: The mean three-dimensional displacement was 2.9 mm for the superior brainstem, 3.4 mm for the inferior brainstem, 3.5 mm for the C1 spine, 5.6 mm for the C6 spine and 6.0 mm for the T2 spine. The lateral aspects of both parotid glands showed a medial translation of 0.85 mm/wk, and glands shrank by 4.9%/wk. The variability of the maximal dose difference was described by standard deviations ranging from 5.6% (upper cord) to 8.0% (lower cord.) The translation of the left parotid resulted in an increase of the mean dose and the volume receiving 26 Gy. CONCLUSION: Random spatial and dosimetric variability is predominant for the brainstem and spinal cord and increases at more inferior locations. In contrast, the parotid glands demonstrated a systematic medial translation during the treatment course and thus sparing may be compromised.

Clinical applications of 3-dimensional printing in radiation therapy.

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy.

Stem cells, senescence, neosis and self-renewal in cancer.

We describe the basic tenets of the current concepts of cancer biology, and review the recent advances on the suppressor role of senescence in tumor growth and the breakdown of this barrier during the origin of tumor growth. Senescence phenotype can be induced by (1) telomere attrition-induced senescence at the end of the cellular mitotic life span (MLS*) and (2) also by replication history-independent, accelerated senescence due to inadvertent activation of oncogenes or by exposure of cells to genotoxins. Tumor suppressor genes p53/pRB/p16INK4A and related senescence checkpoints are involved in effecting the onset of senescence. However, senescence as a tumor suppressor mechanism is a leaky process and senescent cells with mutations or epimutations in these genes escape mitotic catastrophe-induced cell death by becoming polyploid cells. These polyploid giant cells, before they die, give rise to several cells with viable genomes via nuclear budding and asymmetric cytokinesis. This mode of cell division has been termed neosis and the immediate neotic offspring the Raju cells. The latter inherit genomic instability and transiently display stem cell properties in that they differentiate into tumor cells and display extended, but, limited MLS, at the end of which they enter senescent phase and can undergo secondary/tertiary neosis to produce the next generation of Raju cells. Neosis is repeated several times during tumor growth in a non-synchronized fashion, is the mode of origin of resistant tumor growth and contributes to tumor cell heterogeneity and continuity. The main event during neosis appears to be the production of mitotically viable daughter genome after epigenetic modulation from the non-viable polyploid genome of neosis mother cell (NMC). This leads to the growth of resistant tumor cells. Since during neosis, spindle checkpoint is not activated, this may give rise to aneuploidy. Thus, tumor cells also are destined to die due to senescence, but may escape senescence due to mutations or epimutations in the senescent checkpoint pathway. A historical review of neosis-like events is presented and implications of neosis in relation to the current dogmas of cancer biology are discussed. Genesis and repetitive re-genesis of Raju cells with transient "stemness" via neosis are of vital importance to the origin and continuous growth of tumors, a process that appears to be common to all types of tumors. We suggest that unlike current anti-mitotic therapy of cancers, anti-neotic therapy would not cause undesirable side effects. We propose a rational hypothesis for the origin and progression of tumors in which neosis plays a major role in the multistep carcinogenesis in different types of cancers. We define cancers as a single disease of uncontrolled neosis due to failure of senescent checkpoint controls.

A different entity: a population based study of characteristics and recurrence patterns in oropharyngeal squamous cell carcinomas.

BACKGROUND: Cases of squamous cell carcinoma (SCC) of the oropharynx were compared with other head and neck cancer (HNC) anatomic subsites in patients treated at the provincial referral centre for HNC, the Nova Scotia Cancer Centre (NSCC). METHODS: A retrospective chart review was performed on HNC patients assessed at the NSCC between 2010 and 2011. Patient demographics, disease characteristics, treatment details and outcomes, including recurrence rates and survival were collected. Data was collected on new and recurrent cases of HNC. This data was compared between the two types of HNC using chi-square tests for dichotomous categorical variables or Fishers exact test where appropriate. Wald test was used to compare categorical variables with 3 categories. Continuous variables were compared using the non-parametric Wilcoxon test. RESULTS: 318 charts were included in the analysis. 122 (38%) were oropharyngeal squamous cell carcinomas (OPSCCs). In terms of disease characteristics, OPSCCs were more likely to be poorly differentiated/undifferentiated (n = 267, 49(40%) vs 42(21%), p < 0.001), non-keratinizing (n = 169, 25(20%) vs 17(9%), p < 0.001), greater than 2 cm (n = 253, 72(59%) vs 78(40%), p = 0.0061), stage 4 (n = 313, 55(45%) vs 64(33%), p = 0.0315) and have had locoregional nodal spread (n = 315, 103(84%) vs 55(28%), p < 0.001). In the subset of 57 patients that had p16 testing, OPSCCs were more likely to be p16(+) (37(30%) vs 1(1%), p < .001). There were no significant differences in terms of Charlson probability of 10 year survival, smoking or alcohol consumption although OPSCC patients were significantly less likely to have COPD as a co-morbidity (n = 318, 19(16%) vs 53(27%), p = 0.0175). Finally, OPSCCs had less chance for relapse than non-OPSCCs in both univariate (2.119 times less, p=0.0034) and multivariate (1.899 times less, p=0.0505) analyses along with a 1.822 times less overall mortality in a multivariae analysis (p=0.0408). CONCLUSIONS: This analysis suggests that Nova Scotian OPSCCs should be considered distinct from other HNC lesions, most notably in terms of disease characteristics and prognosis. Specifically, despite a higher association with disease factors traditionally considered to be linked to poor prognosis, outcomes were actually superior in terms of relapse and overall mortality.

Investigating the Impact of Positron Emission Tomography-Computed Tomography Versus Computed Tomography Alone for High-risk Volume Selection in Head and Neck and Lung Patients Undergoing Radiotherapy: Interim Findings.

INTRODUCTION: The aim of this study was to quantify the impact of positron emission tomography-computed tomography (PET-CT) on clinical target volume (CTV) selection in non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cancer patients. METHODS: Eight radiation oncologists with expertise in either NSCLC or HNSCC prospectively contoured target volumes with and without PET-CT findings. All volumes were contoured manually, and computed tomography (CT)-alone contours were identified as gross tumour volume CT and clinical target volume (CTV) CT, whereas those contoured with the aid of PET-CT were GTV PET and CTV PET. PET-CT contours were used for actual treatment delivery. Test treatment plans were generated based on the CT-alone volumes and applied to the final PET-CT contours. PET-CT had an impact if the test plans failed department quality assurance guidelines. For each patient, the dose to critical structures and any changes in the treatment plan were recorded. RESULTS: Eighty patients (49 HNSCC and 31 NSCLC) were analyzed. PET-CT impacted 42.9% of HNSCC cases and 45.2% of NSCLC cases. On average, PET-CT volumes were significantly larger than CT-alone volumes for HNSCC cases (P < .01) but not for NSCLC cases (P = .29). For organs at risk, no statistically significant differences were noted, with the exception of mean parotid dose for the right and left parotids (P = .0137and P = .0330, respectively). CONCLUSIONS: Interim analysis of data found that the use of PET-CT in the radiation therapy planning process impacted CTV selection, resulting in a major change in radiation therapy plans in 43.7% (HNSCC 42.9% and NSCLC 45.2%) of patients.

Neosis: a novel type of cell division in cancer.

Using computerized video time-lapse microscopy, we studied early cellular events during carcinogen-induced transformation of C3H10T1/2 cells. Multinucleate/polyploid giant cells (MN/PGs) formed due to DNA damage are thought to die via mitotic catastrophe. Before they die, some MN/PGs undergo a novel type of cell division, termed neosis, characterized by karyokinesis via nuclear budding followed by asymmetric, intracellular cytokinesis, producing several small mononuclear cells, termed the Raju cells, with extended mitotic life span (MLS). Mitotic derivatives of Raju cells give rise to transformed cell lines, inherit genomic instability, display a phenotype and transcriptome different from the neosis mother cell, and anchorage-independent growth. Neosis of MN/PGs also precedes spontaneous transformation of p53-/- mouse cells. Rodent neotic clones, and primary and metastatic human tumor cells undergo spontaneous or induced secondary/tertiary neosis. Neosis seems to extend the MLS of cells under conditions of genetic duress not favoring mitosis. It precedes tumorigenesis, occurs several times during tumor progression, yielding tumor-initiating Raju cells and introducing tumor cell heterogeneity subject to natural selection during tumor progression. Events during neosis, and its relevance to origin of established cell lines, multistep carcinogenesis, cancer stem cells, and therapeutic advantages of anti-neotic agents (neosicides) are discussed.

Is lower socioeconomic status associated with more advanced thyroid cancer stage at presentation? A study in two Canadian centers.

BACKGROUND: Some studies have shown a higher incidence of thyroid cancer in patients with insurance coverage and higher socioeconomic status (SES), and a higher thyroid cancer stage in patients with lower SES, suggesting SES-related health disparity in thyroid cancer. However, it is not known if the same is evident under a universal healthcare system such as that in Canada. METHODS: We used data from the Canadian Thyroid Cancer Consortium, a large thyroid cancer registry that collects data from two major thyroid cancer referral centers (London, Ontario, and Halifax, Nova Scotia). We included patients who presented with thyroid cancer between 1998 and 2011. We determined age at presentation, sex, and thyroid cancer status using the American Joint Committee on Cancer (AJCC) staging criteria. Individuals' postal codes were used to retrieve data from the Canadian census for the years 1996, 2001, and 2006 to approximate household income. Ordered logistic regression was used to determine odds ratios of presenting with more advanced stage thyroid cancer as they relate to income, age, and sex. RESULTS: We included 1701 patients: 1334 cases from London and 367 from Halifax. Thyroid cancer was diagnosed more frequently in the higher SES groups (p<0.001). Compared to patients in the top income quintile, patients in the lowest and second-lowest income quintiles had significantly higher odds of having more advanced stage thyroid cancer at presentation (OR 1.58, p=0.002; 1.37, p=0.024 respectively). CONCLUSIONS: Our study suggests that, similar to countries that lack a universal healthcare system, health disparity in thyroid cancer also exists in Canada. It appears that while thyroid cancers were diagnosed more frequently in Canadian patients of higher SES, Canadian patients in the lower SES groups had more advanced stage thyroid cancer at presentation.

Management of differentiated thyroid cancer in pregnancy.

In young women, differentiated thyroid cancer is the second most common malignancy diagnosed around the time of pregnancy. Management of thyroid cancer during pregnancy poses distinct challenges due to concerns regarding maternal and fetal well-being. In most cases surgery can be safely delayed until after delivery and with adequate management and outcome of pregnancy in women with thyroid cancer is excellent. Ideally these patients should be managed by a multidisciplinary team, and management plan should be determined by a consensus between the patient and the healthcare team.