Prescribing and evaluating target dose in dose-painting treatment plans

<div><p></p><p><b>Background.</b> Assessment of target dose conformity in multi-dose-level treatment plans is challenging due to inevitable over/underdosage at the border zone between dose levels. Here, we evaluate different target dose prescription planning aims and approaches to evaluate the relative merit of such plans. A quality volume histogram (QVH) tool for history-based evaluation is proposed.</p><p><b>Material and methods.</b> Twenty head and neck cancer dose-painting plans with five prescription levels were evaluated, as well as clinically delivered simultaneous integrated boost (SIB) plans from 2010 and 2012. The QVH tool was used for target dose comparison between groups of plans, and to identify and improve a suboptimal dose-painting plan.</p><p><b>Results.</b> Comparison of 2010 and 2012 treatment plans with the QVH tool demonstrated that 2012 plans have decreased underdosed volume at the expense of increased overdosed volume relative to the 2010 plans. This shift had not been detected previously. One suboptimal dose-painting plan was compared to the ‘normal zone’ of the QVH tool and could be improved by re-optimization.</p><p><b>Conclusion.</b> The QVH tool provides a method to assess target dose conformity in dose-painting and multi-dose-level plans. The tool can be useful for quality assurance of multi-center trials, and for visualizing the development of treatment planning in routine clinical practice.</p></div

Increasing incidence and survival of head and neck cancers in Denmark: a nation-wide study from 1980 to 2014

<p><b>Background:</b> The purpose of the study was to determine trends in age-adjusted incidence rates (AAIR) and survival probability in head and neck cancers (HNCs) in the Danish population from 1980 to 2014.</p> <p><b>Material and methods:</b> All patients registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014 were included. We evaluated the AAIR per 100,000 and the average annual percent change (AAPC). The relative survival probability at 5 years was calculated in relation to gender, anatomical location and histology, and we constructed age-period-cohort models of incidence.</p> <p><b>Results:</b> About 34,606 patients were included (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000 in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%). Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men (1.6%). For all HNC patients, the relative survival at 5 years rose significantly from 49.0% in 1980–1984 to 62.4% in 2010–2014. Women had a significantly higher survival than men with a relative survival of 61.7% compared to 50.0% in men. Laryngeal cancer had the best survival probability of cancers in the upper aerodigestive tract with hypopharyngeal cancer having the poorest survival.</p> <p><b>Conclusion:</b> This nation-wide study showed a significant rise in incidence of HNC for men and women along with a significant increase in relative survival. Oropharyngeal cancer had the highest increase in incidence followed by hypopharyngeal cancer which showed the poorest survival of HNCs.</p

Incidence and survival of oropharyngeal cancer in Denmark: a nation-wide, population-based study from 1980 to 2014

<p><b>Background:</b> Oropharyngeal carcinomas (OPCs) constitute a significant and increasing proportion of head and neck carcinomas and are an important global cause of morbidity and mortality. The purpose of this study was to determine trends in incidence and survival in OPC in the Danish population from 1980 to 2014.</p> <p><b>Methods:</b> This study included all patients registered in the nationwide Danish Cancer Registry over the period 1980–2014. The age-adjusted incidence rates (AAIR) per 100,000, annual percentage change (APC) and average annual percent change (AAPC) were evaluated. Five-year relative survival (RS) was calculated with Cox regression analyses in relation to gender, anatomical location and histology.</p> <p><b>Results:</b> A total of 6555 patients (69% male) were included, with a median age at diagnosis of 60 years. The AAIR of patients with OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period 1980–1984 to 58.5% (25.4% points) over the period 2010–2014. With no significant difference stratified for gender. Tumors located at the palatine tonsils (<i>n</i> = 3333) and salivary gland OPC (<i>n</i> = 90) had significantly better survival compared with other sub-locations and histology subtypes. In the APC model the birth cohort effect rate ratio increased until 1925 and then decreased until 1935 from which point it increased in the last cohorts.</p> <p><b>Conclusions:</b> In this population-based study, we observed a significant increase in the incidence of OPCs and in the RS for OPC. We also identified a profound birth cohort effect on the incidence.</p

Additional file 3: of Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature

Figure S2. MATH scores. Example of the mutant-allele tumor heterogeneity (MATH) scores, as a measure of tumor heterogeneity. The higher the math-score the higher the tumor heterogeneity. Mid right: Histogram of the MATH-score in the entire cohort. (JPG 201 kb

The miR-21 in situ hybridization is specific.

<p>Comparison between the miR-21 probe (A) and the scrambled probe (B) in the same tumor. The scrambled probe (B) gave no expression. Comparison between miR-21 probe (C) and U6 probe (D) in the same tumor. The U6 probe gives a positive nuclear expression in virtually every cell.</p

Human Papillomavirus in Head and Neck Squamous Cell Carcinoma of Unknown Primary Is a Common Event and a Strong Predictor of Survival

<div><p>Background</p><p>The purpose of this study was to examine the prevalence of human papillomavirus (HPV) in patients with head and neck squamous cell carcinoma of unknown primary (CUP).</p><p>Methods</p><p>All patients diagnosed with and treated for CUP between January 1, 2000, and June 1, 2011, at two Danish medical centers were included. All patients received a thorough diagnostic work-up, including FDG-PET, before being diagnosed as CUP. We determined the HPV status in all patients using a combination of HPV DNA PCR and p16 stain. In addition, clinical information on the study patients was retrieved from clinical records.</p><p>Results</p><p>Of the identified 60 patients with CUP, 13 were shown to be positive for HPV DNA, amounting to 22% of the study population. In addition, we were able to show a clear disease-free and overall-survival benefit in the HPV-positive group, with a hazard ratio of 0.16 (95% CI: 0.038–0.67) for over-all survival. This survival benefit was also apparent when adjusted for advanced age in a multivariate Cox regression analysis.</p><p>Conclusion</p><p>A fairly large percentage of CUP cases are HPV-related, and because this is related to both the location and prognosis, we recommend HPV testing as part of the diagnostic work-up.</p></div

Hazard ratios from univariate analysis for disease free survival in OSCC.

<p>On the right hazard ratios including 95% confidence intervals are displayed. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095193#pone-0095193-t001" target="_blank">Table 1</a> for details.</p

miR-21 is mainly expressed in the tumor stroma in OSCC.

<p>(A) An overview image of miR-21 expression where the areas marked by rectangles are magnified in, (B) normal oral mucosa, (C) mild epithelial dysplasia and (D) oral squamous cell carcinoma. Mir-21 appears as a blue stain. In normal oral mucosa, (B) no miR-21 expression is observed, whereas in dysplasia, (C) a weak expression is seen in the subepithelial connective tissue, and a widespread and intense expression is found in the tumor stromal compartment (D). Panels (E), (F) and (G) illustrate combined FISH and IF for miR-21 (E), α-SMA (F) and a composite image (G) showing a high degree of overlap between the two markers.</p

Multivariate model of factors associated with disease free survival.

<p>Legend: The remaining factors in multivariate Cox regression after backwards elimination. Only miR-21 TBS and perineural invasion remained as independent factors influencing survival.</p

Digital image analysis of in situ hybridization.

<p>The miR-21 expression in the stroma was estimated using digital image analysis. Image (A), (B), (C) and (D) overview the image-analysis process, where (A) is the original cytokeratin stained image, which is used to delineate epithelial tumor cells, seen as green color in (B). Original image of miR-21 ISH on serial section from same tumor, where the ISH signal is quantitated specifically in the stroma area (blue signal). The red color in (B) represents stroma area negative for miR-21. See methods for a detailed description of the image analysis process.</p