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Bulk transcriptomes are an essential data resource for understanding basic and disease biology. However, integrating information from different experiments remains challenging because of the batch effect generated by various technological and biological variations in the transcriptome. Numerous batch-correction methods to deal with this batch effect have been developed in the past. However, a user-friendly workflow to select the most appropriate batch-correction method for the given set of experiments is still missing. We present the SelectBCM tool that prioritizes the most appropriate batch-correction method for a given set of bulk transcriptomic experiments, improving biological clustering and gene differential expression analysis. We demonstrate the applicability of the SelectBCM tool on analyses of real data for two common diseases, rheumatoid arthritis and osteoarthritis, and one example to characterize a biological state, where we performed a meta-analysis of the macrophage activation state. The R package is available at https://github.com/ebi-gene-expression-group/selectBCM.

The growing number of available single cell gene expression datasets from different species creates opportunities to explore evolutionary relationships between cell types across species. Cross-species integration of single-cell RNA-sequencing data has been particularly informative in this context. However, in order to do so robustly it is essential to have rigorous benchmarking and appropriate guidelines to ensure that integration results truly reflect biology. We benchmarked 28 combinations of gene homology mapping methods and data integration algorithms in a variety of biological settings. We examined the capability of each strategy to perform species-mixing of known homologous cell types and to preserve biological heterogeneity using 9 established metrics. We also developed a new biology conservation metric to address the maintenance of cell type distinguishability. Overall, scANVI, scVI and SeuratV4 methods achieved a balance between species-mixing and biology conservation. For evolutionarily distant species, including in-paralogs was beneficial. SAMap outperformed when integrating whole-body atlases between species with challenging gene homology annotation. We provided our freely available cross-species integration and assessment pipeline to help analyse new data and develop new algorithms.

To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAFThis phase 1b, open-label, international multicentre study enrolled 3 cohorts. Herein, we report on patients in cohorts A and B who had progressed on prior anti‒PD-1 therapy. Patients in cohort A received cobimetinib 60 mg once daily for 21 days followed by a 7-day break and concurrent intravenous atezolizumab 840 mg every 2 weeks. Patients in cohort B received the same dosing regimen as cohort A except for cycle 1 in which patients received cobimetinib only for the first 14 days prior to initiation of atezolizumab on cycle 1 day 15. Coprimary end-points were objective response rate and disease control rate. Secondary end-points were duration of response, progression free survival and overall survival.Between 19th June 2017 and 12th December 2018, 103 patients were enrolled. Median follow-up was 6.9 months (interquartile range, 4.8-10.1 months); objective response rate was 14.6% and disease control rate was 38.8% (95% confidence interval, 29.39-48.94). The median duration of response, progression-free survival and overall survival was 12.7 months, 3.8 months and 14.7 months, respectively. The most common adverse events were diarrhoea (75/103; 72.8%), dermatitis acneiform (57/103; 55.3%) and nausea (52/103; 50.5%). Thirty-four patients (33.0%) died: 33 (91.7%) due to progressive disease and one (1%) due to treatment-related oesophagitis.Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAFThis study is registered with ClinicalTrials.gov; NCT03178851.

In this study, we conducted two cruises in the Bohai Bay (China) focusing on phytoplankton community and relation to water quality. The evaluation revealed that most of the open area was non-eutrophic, whereas the river inlet had severe eutrophication. Phytoplankton populations respond differently to different aquatic environments and are controlled by more than two factors, as revealed by aggregated boosted tree analysis. Notably, a shift in the phytoplankton community structure was observed during the seasonal transition, from the dominance of diatoms to the co-dominance of diatoms-dinoflagellates. However, the relative abundance of dinoflagellates increased by 14 % in autumn, when the harmful algae species Akashiwo sanguinea exclusively predominated; this was primarily linked to the nutrient ratios, temperature, and dissolved oxygen. The eutrophication and organic pollution had direct effects on phytoplankton abundance. Overall, our findings may provide further insights into the impacts of eutrophic environments on phytoplankton community structure in coastal systems.

The effects of itraconazole, a strong CYP3A4 inhibitor, on the steady-state pharmacokinetics of vemurafenib were evaluated in a phase 1, multicenter, open-label, fixed-sequence study. Patients with BRAFV600 mutation-positive metastatic malignancies received oral vemurafenib 960 mg twice daily on days 1 to 20 (period A) and oral vemurafenib 960 mg twice daily with oral itraconazole 200 mg once daily on days 21 to 40 (period B). A mixed-effects analysis of variance model was used to compare log-transformed area under the concentration-time curve during the dosing interval and maximum plasma concentration values for vemurafenib in 8 patients between period B (vemurafenib plus itraconazole) and period A (vemurafenib alone). Multiple doses of itraconazole increased steady-state exposure of vemurafenib by approximately 40%, with geometric least squares mean ratios (period B/period A) of 140% (90% confidence interval, 121-161) for both maximum plasma concentration and area under the concentration-time curve during the dosing interval. There was no apparent increase in incidence or severity of adverse events during coadministration of vemurafenib with itraconazole. In conclusion, coadministration of itraconazole with vemurafenib resulted in a modest increase in exposure of vemurafenib at steady state and was generally well tolerated.

Smoking cessation is an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient awareness of the harms of continued smoking. Cancer survivors from Princess Margaret Cancer Centre (Toronto, ON) were surveyed on their awareness of the harms of continued smoking on cancer-related outcomes. Multivariable logistic regression models assessed factors associated with awareness and whether awareness was associated with subsequent cessation among smokers at diagnosis. Among 1118 patients, 23% were current smokers pre-diagnosis and 54% subsequently quit; 25% had lung and 30% head and neck cancers. Many patients reported being unaware that continued smoking results in greater cancer surgical complications (53%), increased radiation side effects (62%), decreased quality of life during chemotherapy (51%), decreased chemotherapy or radiation efficacy (57%), increased risk of death (40%), and increased development of second primaries (38%). Being a current smoker was associated with greater lack of awareness of some of these smoking harms (aORs = 1.53–2.20, P < 0.001–0.02), as was exposure to any second-hand smoke (aORs = 1.45–1.53, P = 0.006–0.04) and being diagnosed with early stage cancer (aORs = 1.38–2.31, P < 0.001–0.06). Among current smokers, those with fewer pack-years, being treated for cure, or had a non-tobacco-related cancer were more likely unaware. Awareness that continued tobacco use worsen quality of life after chemotherapy was associated with subsequent cessation (aOR = 2.26, P = 0.006). Many cancer survivors are unaware that continued smoking can negatively impact cancer-related outcomes. The impact of educating patients about the potential harms of continued smoking when discussing treatment plans should be further evaluated.

Highlights • Tissue segmentation can be achieved using a spatially registered cytokeratin mask. • Automated and manual cell counts and stain intensities were highly correlated. • Smokers had significantly stronger PD-L1 stain intensity and higher numbers TILs. • After radiotherapy, greater CD8+ TILs was associated with inferior survival., Oral tongue squamous cell carcinoma (OTSCC) displays variable levels of immune cells within the tumor microenvironment. The quantity and localization of tumor infiltrating lymphocytes (TILs), specific functional TIL subsets (e.g., CD8+), and biomarker-expressing cells (e.g., PD-L1+) may have prognostic and predictive value. The purpose of this study was to evaluate the robustness and utility of computer-assisted image analysis tools to quantify and localize immunohistochemistry-based biomarkers within the tumor microenvironment on a tissue microarray (TMA). We stained a 91-patient OTSCC TMA with antibodies targeting CD3, CD4, CD8, FOXP3, IDO, and PD-L1. Cell populations were segmented into epithelial (tumor) or stromal compartments according to a mask derived from a pan-cytokeratin stain. Definiens Tissue Studio was used to enumerate marker-positive cells or to quantify the staining intensity. Automated methods were validated against manual tissue segmentation, cell count, and stain intensity quantification. Univariate associations of cell count and stain intensity with smoking status, stage, overall survival (OS), and disease-free survival (DFS) were determined. Our results revealed that the accuracy of automated tissue segmentation was dependent on the distance of the tissue section from the cytokeratin mask and the proportion of the tissue containing tumor vs. stroma. Automated and manual cell counts and stain intensities were highly correlated (Pearson coefficient range: 0.46–0.90; p

This paper deals with stiffness modeling of a novel parallel 2-DOF solar tracker with high rigidity and large workspace to track the sun. An analytical method to derive the stiffness matrix of universal joint in non-diagonal form is proposed. Considering the influence of universal joint stiffness on the deformation of solar tracker, the stiffness matrix of the solar tracker is derived with Matrix Structural Analysis method. The simulation on the stiffness of the solar tracker is carried out. A stiffness measuring mechanism is designed to measure the stiffness of the solar tracker and the experimental results are compared with the stiffness value from the stiffness model to validate the effectiveness of the modeling method.

Objectives Short stature and thyroid autoimmunity are common comorbidities in Turner syndrome (TS). Recombinant human growth hormone (rhGH) significantly improves height growth in TS individuals. This study aims to investigate the association of thyroid autoimmunity and the response to rhGH treatment in TS patients. Methods Medical records of 494 patients with TS were reviewed. Among 126 patients who regularly tested for thyroid autoantibodies, 108 patients had received rhGH treatment. Clinical characteristics, including karyotype and the presence of autoimmune thyroid diseases, as well as rhGH treatment records were analyzed. Height velocity (HV) of patients with or without thyroid autoimmunity was compared to assess the response to rhGH treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HV before and after antibody presence were compared. Results 45XO monosomy presented in 36% (176/496) of patients. 42.1% of patients (53/126) had elevated circulating anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. In 108 patients who received rhGH treatment, HVs were significantly correlated to age, height, weight and BMI at the initiation of treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HVs after thyroid autoantibody presence significantly decreased compared with HVs before thyroid autoantibody detection (n=44, p=0.0017). Conclusions Our data suggested that in TS patients who developed thyroid autoantibodies during rhGH treatment, the response to rhGH is negatively associated with the development of thyroid autoimmunity.

Objective To identify any association between type 2 diabetes mellitus (T2DM) and survival outcomes for mucosal squamous cell carcinoma of the head and neck. An association has been demonstrated between T2DM and cancer outcomes at numerous sites, but data for the head and neck are limited. Improving our understanding of the impact that diabetes has on head and neck cancer survival is relevant for making treatment decisions and counseling patients regarding prognosis. Study Design Retrospective cohort study. Setting Academic tertiary referral head and neck cancer center. Subjects and Methods By accessing data retrospectively from prospectively collected databases at the Princess Margaret Cancer Centre, patients were studied who were treated for mucosal head and neck squamous cell cancer between January 2005 and December 2011. Collection of clinical, pathologic, and survival data was completed with an emphasis on T2DM. Results Of 2498 patients identified in the study period, 319 (12.8%) had T2DM. Five-year overall survival was not different between the diabetic (64%, 95% CI = 58%-71%) and nondiabetic (67%, 95% CI = 65%-69%; P = .078) groups. Furthermore, cause-specific survival did not demonstrate a statistically significant difference between groups (diabetic: 84%, 95% CI = 79%-88%, vs nondiabetic: 84%, 95% CI = 82%-86%; P = .67). Conclusion Despite contradictory evidence at other cancer sites, the presence of T2DM alone does not appear to adversely affect cancer survival outcomes in head and neck squamous cell cancer. This is encouraging for the diabetic patients with head and neck squamous cell cancer, and it provides guidance for the multidisciplinary team that treats them.

Background Body mass index (BMI) has been associated variably with head and neck cancer outcomes. We evaluated the association between BMI at either diagnosis or at early adulthood head and neck cancer outcomes. Methods Patients with invasive head and neck squamous cell cancer at Princess Margaret Cancer Centre in Toronto, Canada, were surveyed on tobacco and alcohol exposure, performance status, comorbidities, and BMI at diagnosis. A subset also had data collected for BMI at early adulthood. Results With a median follow-up of 2.5 years, in 1279 analyzed patients, being overweight (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.4-0.8; p = .001) at diagnosis was associated with improved survival when compared with individuals with normal weight. In contrast, underweight patients at diagnosis were associated with a worse outcome (HR, 1.89; 95% CI, 1.2-3.1; p Conclusion Being underweight at diagnosis was an independent, adverse prognostic factor, whereas being overweight conferred better prognosis. BMI in early adulthood was not associated strongly with head and neck cancer outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1226-1233, 2017.

The effects of itraconazole, a strong CYP3A4 inhibitor, on the steady-state pharmacokinetics of vemurafenib were evaluated in a phase 1, multicenter, open-label, fixed-sequence study. Patients with BRAF

This paper deals with dynamic analysis of a 5-DOF hybrid machine tool by using its scale model considering the geometrically distorted revolute joint. Geometric distortion of revolute joint can reduce the accuracy of similitude analysis by causing partial similitude problem. To solve this, scaling laws related to dynamic characteristics are derived, and those may not invariants in partial similitude problem are figured out. Then, the effects of revolute joint properties on dynamic characteristics are investigated. Based on this, the partial similitude problem is eliminated by relaxing scaling laws with little influence on the analysis. The scaling factors of dynamic characteristics are derived according to the reserved scaling laws. Finally, the predicted dynamic characteristics, including natural frequencies and mode shapes, of the full-size machine tool are obtained from its scale model.

Aim The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methods A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. Results A total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin 200 mg/m 2 subgroups were 52%, 60%, and 72% ( P = 0.001) for the HPV− and 91%, 90%, and 91% ( P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m 2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset ( N = 107) with cisplatin >200 mg/m 2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). Conclusions A survival benefit of cisplatin dose >200 mg/m 2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.

Background The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers. Methods T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/− chemotherapy) (RT/CRT) and primary surgery cohorts. Results Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery (p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p < .01). Conclusion Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

This paper predicts the dynamic characteristics of a 5-DOF hybrid machine tool by using scale model, and the geometric distortion of bearings is considered in the study. As the distortion causes scaling laws related to rotational joint properties to vary between the full-size system and scale model, the effects of revolute mass and stiffness on the dynamic characteristics of the 5-DOF hybrid machine tool are investigated. On this basis, the scaling laws related to rotational joint mass and axial stiffness are relaxed as they have little effect on the dynamic characteristics of hybrid machine tool. Moreover, bearing radial stiffness has significant influence on the dynamic characteristics, and it is selected as the fundamental scaling parameter, because the standard bearing cannot be scaled down in arbitrary ratio. Thus, the scaling factors of parameters shown in the scaling laws are determined on the basis of bearing radial stiffness. Considering the effect of the complex contact between roller and raceway on the radial stiffness, the scaling factor of bearing radial stiffness is obtained through experiments on bearing axial stiffness. Subsequently, dimension parameters of the scale model are obtained, and the scaling factor of the dynamic characteristics of the hybrid machine tool are derived. Finally, dynamic characteristics of the full-size hybrid machine tool and its scale model are simulated through structural dynamics to validate the dynamic characteristics prediction.

BACKGROUND: The Hedgehog (Hh) signaling pathway is active in esophageal adenocarcinoma (EAC). We used a patient-derived murine xenograft (PDX) model of EAC to evaluate tumour response to conventional treatment with radiation/chemoradiation with or without Hh inhibition. Our goal was to determine the potential radioresistance effects of Hh signaling and radiosensitization by Hh inhibitors.METHODS: PDX models were treated with radiation, chemotherapy or combined chemoradiation. Tumour response was measured by growth delay. Hh transcript levels (qRT-PCR) were compared among frozen tumours from treated and control mice. 5E1, a monoclonal SHH antibody, or LDE225, a clinical SMO inhibitor (Novartis®) inhibited Hh signaling.RESULTS: Precision irradiation significantly delayed xenograft tumour growth in all 7 PDX models. Combined chemoradiation further delayed growth relative to either modality alone in three of six PDX models. Following irradiation, two of three PDX models demonstrated sustained up-regulation of Hh transcripts. Combined LDE225 and radiation, and 5E1 alone delayed growth relative to either treatment alone in a Hh-responsive PDX model, but not in a non-responsive model.CONCLUSION: Hh signaling mediates the radiation response in some EAC PDX models, and inhibition of this pathway may augment the efficacy of radiation in tumours that are Hh dependent.

Purpose: Continued smoking after a cancer diagnosis leads to poorer treatment outcomes, survival, and quality of life. We evaluated the perceptions of the effects of continued smoking on quality of life, survival, and fatigue among patients with cancer after a cancer diagnosis and the effects of these perceptions on smoking cessation. Patients and Methods: Patients with cancer from all disease subsites from Princess Margaret Cancer Centre (Toronto, Ontario) were surveyed between April 2014 and May 2016 for sociodemographic variables, smoking history, and perceptions of continued smoking on quality of life, survival, and fatigue. Multivariable regression models evaluated the association between patients’ perceptions and smoking cessation and the factors influencing patients’ perceptions of smoking. Results: Among 1,121 patients, 277 (23%) were smoking cigarettes up to 1 year before diagnosis, and 54% subsequently quit; 23% had lung cancer, and 27% had head and neck cancers. The majority felt that continued smoking after a cancer diagnosis negatively affected quality of life (83%), survival (86%), and fatigue (82%). Current smokers during the peridiagnosis period were less likely to perceive that continued smoking was harmful when compared with ex-smokers and never-smokers ( P < .01). Among current smokers, perceiving that smoking negatively affected quality of life (adjusted odds ratio [aOR], 2.68 [95% CI, 1.26 to 5.72]; P = .011), survival (aOR, 5.00 [95% CI, 2.19 to 11.43]; P < .001), and fatigue (aOR, 3.57 [95% CI, 1.69 to 7.54]; P < .001) were each strongly associated with smoking cessation. Among all patients, those with a greater smoking history were less likely to believe that smoking was harmful in terms of quality of life (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), survival (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), and fatigue (aOR, 0.99 [95% CI, 0.98 to 0.99]; P < .001). Conclusion: The perceptions of continued smoking after a cancer diagnosis among patients with cancer are strongly associated with smoking cessation. Counseling about the harms of continued smoking in patients with cancer, and in particular among those who have lower risk perceptions, should be considered when developing a smoking cessation program.

Importance Transoral robotic surgery– or transoral laser microsurgery–assisted lingual tonsillectomy may improve the identification rate of hidden base-of-tongue (BOT) carcinoma presenting as head or neck carcinoma of unknown primary (CUP) site. Objective To evaluate the potential impact of lingual tonsillectomy in CUP site by comparing differences in radiotherapy volumes, dosimetry, and clinical outcomes for CUP site and T1-category BOT carcinoma. Design, Setting, and Participants Retrospective study of 115 patients treated at a tertiary cancer center between January 1, 2005, and December 31, 2013, that included patients with BOT carcinoma (category T1N1-3M0) and CUP site (category T0N1-3M0) with known p16 status. Fifty-four patients with T1-category BOT carcinoma (50 [92.6%] p16-positive) were treated with definitive intensity-modulated radiotherapy (IMRT), including 34 (63%) who received concurrent chemotherapy. Sixty-one patients with CUP site (38 [62.3%] p16-positive) received definitive (42 [68.9%]) or postoperative (19 [31.1%]) IMRT, including 22 (36%) who received concurrent chemotherapy. Interventions Definitive or postoperative IMRT, with or without concurrent chemotherapy. Main Outcomes and Measures Characteristics of mucosal clinical target volume (CTV-T), nodal CTV, and organ-at-risk dosimetry; local, regional, and distant control; cause-specific and overall survival; and Radiation Therapy Oncology Group grade 3 or higher late toxic effects. Results Of 115 participants, 104 (90.4%) were male; mean (SD) age was 59 (10) years. High-dose CTV-T was prescribed in all 54 patients with BOT carcinoma and 23 (37.7%) with CUP site (effect size [Δ], 62%; 95% CI, 50%-74%). Low-dose CTV-T included mucosal pharyngeal sites outside the oropharynx in no patients with BOT carcinoma and 26 (42.6%) (95% CI, 30%-54%) with CUP site, with greater low-dose CTV-T volume in CUP site than BOT carcinoma (113 vs 84 cm 3 ; Δ, 30 cm 3 ; 95% CI, 10-49 cm 3 ). Bilateral neck irradiation was used in 53 of 54 patients (98.1%) with BOT carcinoma and 46 of 61 (75.4%) with CUP site (Δ, 23%; 95% CI, 12% to 34%). Patients with BOT carcinoma received a higher maximum dose to the mandible (71 vs 67.2 Gy; Δ, 3.8 Gy; 95% CI, 1.6 to 6 Gy), with a nonsignificantly higher maximum dose (66.1 vs 62.8 Gy; 3.2 Gy; 95% CI, −0.1 to 6.5 Gy) and lower mean dose to the larynx (43.8 vs 47.1 Gy; 3.3 Gy; 95% CI, −0.3 to 6.9 Gy). There were no significant differences in local control, regional control, distant control, cause-specific survival, and overall survival between the BOT carcinoma and CUP site groups stratified by p16 status. Grade 3 Radiation Therapy Oncology Group late toxic effects occurred in 2 patients (3.3%) with CUP site (both neck fibrosis) and 5 (9.3%) with BOT carcinoma (2 neck fibrosis, 2 osteoradionecrosis, and 1 dysphagia). Conclusions and Relevance Intensity-modulated radiotherapy for CUP site or T1-category BOT carcinoma had similar clinical outcomes. Identifying hidden BOT primary carcinoma with novel approaches (eg, transoral robotic surgery and transoral laser microsurgery) may lead to changes in the radiotherapy target volume and dose prescription. Studies are needed to investigate the effect of these differences on quality of life and functional outcomes.

To explore the impact of tumor human papillomavirus (HPV) status, comorbidity, polypharmacy, and treatment intensity on overall survival (OS) of elderly oropharyngeal cancer (OPC) patients.All elderly (70 years) OPC patients receiving definitive (chemo-) radiation therapy in 2000 to 2013 were reviewed. Charlson comorbidity index (CCI, comorbidity alone) and the comorbidity-polypharmacy score (CPS, comorbidity and medication) were calculated. Overall survival was compared between HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Multivariable analyses (MVA) incorporating either the CCI (MVA-CCI) or the CPS (MVA-CPS) identified survival predictors.Among 231 of 287 patients (80%) with p16 staining, 117 were HPV+ and 114 HPV-. Systemic treatments were administered in 48 patients (21%) (chemotherapy 17; epidermal growth factor receptor inhibitor 31). The distribution of CCI (P=.59), CPS (P=.23), and age (P=.50) were similar between HPV+ versus HPV- cohorts. Median follow-up was 4.3 years. The HPV+ patients had better 5-year OS (57% vs 32%, P.001) versus HPV- patients. Multivariable analysis adjusted for T-/N-category confirmed that HPV+ status (MVA-CCI: hazard ratio [HR] 0.58, P=.01; MVA-CPS: HR 0.60, P=.02), Zubrod scale score (0-1) (MVA-CCI: HR 0.44, P.001; MVA-CPS: HR 0.43, P.001), and higher radiation therapy dose (MVA-CCI: HR 0.97, P=.001; MVA-CPS: HR 0.96, P.001) were correlated with higher OS. A marginal inverse correlation between CPS and OS was observed in the entire cohort (HR 1.05, P=.05) and was stronger for the HPV+ cohort (HR 1.11, P=.02). Nonsignificant higher OS was also found with ≤20 pack-years of smoking (MVA-CCI: P=.10; MVA-CPS: P=.15) and with systemic treatments (MVA-CCI: P=.13; MVA-CPS: P=.19). No association with OS was found for CCI (P=.46).Elderly HPV+ OPC patients have longer survival than their HPV- counterparts. Lower Zubrod scale score and higher radiation therapy dose are associated with longer OS, whereas fewer smoking pack-years and systemic agents have nonsignificant associations. Comorbidity-polypharmacy score, but not CCI, is correlated with OS, especially in HPV+ patients, suggesting the potential importance of assessing polypharmacy in addition to comorbidity burden in this population.

The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers.T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/- chemotherapy) (RT/CRT) and primary surgery cohorts.Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery (p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p.01).Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2035-E2040, 2016.

Body mass index (BMI) has been associated variably with head and neck cancer outcomes. We evaluated the association between BMI at either diagnosis or at early adulthood head and neck cancer outcomes.Patients with invasive head and neck squamous cell cancer at Princess Margaret Cancer Centre in Toronto, Canada, were surveyed on tobacco and alcohol exposure, performance status, comorbidities, and BMI at diagnosis. A subset also had data collected for BMI at early adulthood.With a median follow-up of 2.5 years, in 1279 analyzed patients, being overweight (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.4-0.8; p = .001) at diagnosis was associated with improved survival when compared with individuals with normal weight. In contrast, underweight patients at diagnosis were associated with a worse outcome (HR, 1.89; 95% CI, 1.2-3.1; p.01).Being underweight at diagnosis was an independent, adverse prognostic factor, whereas being overweight conferred better prognosis. BMI in early adulthood was not associated strongly with head and neck cancer outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1226-1233, 2017.

The prognostic significance of human papillomavirus (HPV) in the context of head and neck squamous cell carcinoma (HNSCC) of cancer of unknown primary (CUP) origin is unclear.Patients treated for CUP at the Princess Margaret Cancer Centre between 2001 and 2013 were stratified by p16 status and retrospectively reviewed.Of the 73 patients included, those with p16-positive tumors (63%) had less advanced nodal status (N1-N2b; 52% vs 89%; p = .035) and less aggressive treatment. Patients with p16-positive tumors had improved 3-year disease-free survival (DFS; 79% vs 56%; p = .012) independent of nodal status and treatment in multivariable analysis (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.08-0.95).Among patients with CUP, p16-positive status is an independent predictor of DFS but not overall survival (OS). © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38: 1347-1353, 2016.

Improved cancer screening and treatment have led to a greater focus on cancer survivorship care. Older cancer survivors may be a unique population. We evaluated whether older cancer survivors (age ≥ 65 years) had lifestyle behaviors, attitudes, and knowledge distinct from younger survivors.Adult cancer survivors with diverse cancer subtypes were recruited from Princess Margaret Cancer Centre (Toronto, Ontario, Canada). Multivariable models evaluated the effect of age on smoking, alcohol, and physical activity habits, attitudes toward and knowledge of these habits on cancer outcomes, and lifestyle information and recommendations received from health care providers, adjusted for sociodemographic and clinicopathologic covariates.Among the 616 survivors recruited, 23% (n = 139) were older. Median follow-up since diagnosis was 24 months. Older survivors were more likely ex-smokers and less likely current smokers than younger survivors, but they were less likely to know that smoking could affect cancer treatment (adjusted odds ratio [OR], 0.53; P = .007) or prognosis (adjusted OR, 0.53; P = .008). Older survivors were more likely to perceive alcohol as improving overall survival (adjusted OR, 2.39; P = .02). Rates of meeting moderate-to-vigorous physical activity guidelines 1 year before diagnosis (adjusted OR, 0.55; P = .02) and maintaining and improving their exercise levels to meet these guidelines after diagnosis (adjusted OR, 0.48; P = .02) were lower in older survivors. Older and younger cancer survivors reported similar rates of receiving lifestyle behavior information from health care providers (P = .36 to .98).Older cancer survivors reported being less aware of the impact of smoking on their overall health, more likely perceived alcohol as beneficial to survival, and were less likely to meet exercise goals compared with younger survivors. Survivorship programs need to consider age when counseling on lifestyle behaviors.

BACKGROUND The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. METHODS The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. RESULTS The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. CONCLUSIONS GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.

179 Background: Smoking cessation is becoming an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient knowledge of the harms of continued smoking. Methods: Patients with various cancer subtypes were surveyed with respect to self-awareness of the harms of continued smoking on cancer outcomes. Multivariable logistic regression models assessed factors associated with the level of awareness. Results: Among 985 patients, 23% smoked at diagnosis; 34% quit > 1 year prior to diagnosis; 25% had lung, 30% had head and neck cancers; 77% received curative therapy. Many patients reported being unaware that smoking can negatively impact cancer surgery (65%), radiation (74%), chemo outcomes (64%), treatment efficacy (70%), cancer prognosis (54%) and second primary development (52%). Among all patients, those smoking at diagnosis were significantly more likely to be unaware of radiation (aOR = 1.73, 95% CI [1.16-2.57]) and chemo (aOR = 2.10 [1.17-3.79]) toxicities, cancer prognosis (aOR = 1.63 [1.16-2.29]) and second primary risk (aOR = 1.61 [1.14-2.26]). Those with poorer health status were more likely unaware of effects on prognosis (aOR = 1.56 [1.18-2.08]) and second primaries (aOR = 1.54 [1.14-2.08]). Patients with non-tobacco related cancers (non-TRCs) were more likely unaware smoking impacts cancer surgery (aOR = 1.45 [1.04-2.04]) and radiation (aOR = 1.37 [1.01-1.85]). Among smokers at diagnosis, those with non-TRCs (aOR = 4.00 [1.45-11.11]) were more likely unaware smoking can impact chemo outcomes. Awareness was not associated with stage, second-hand smoke exposure, cessation or interest in a smoking cessation program (SCP), but was associated with patients believing that a SCP would be beneficial to their health (aORs = 2.33-4.35, P < 0.03). Among smokers at diagnosis, believing that a SCP is beneficial (51%) was associated with both interest in an in-patient (aOR = 4.65 [2.15-10.03]) and ambulatory (aOR = 4.08 [2.14-7.79]) SCP. Conclusions: Many cancer patients were unaware of the harms of continued smoking; mainly smokers at diagnosis and those with non-TRCs. Patient education should focus on emphasizing awareness, which may help improve patient interest in smoking cessation.

251 Background: With improvements in cancer therapies, palliative patients with cancer now enjoy improved and sometimes prolonged survival. Continued smoking after a cancer diagnosis negatively impacts treatment response/toxicities, survival and quality of life and is influenced by SHS exposure. Little is known about the perceptions of palliative patients with cancer in comparison to patients who are considered potentially curative, on smoking after a cancer diagnosis and of SHS exposure. We assessed such potential differences in perception. Methods: Patients with cancer across all sites were surveyed with respect to their smoking habits and perceptions on how smoking and SHS influences cancer-related QofL, fatigue and overall survival (OS). Review of patient charts confirmed which patients were considered palliative versus potentially curative. Multivariable logistic regression models assessed for associations between treatment intent and patient perceptions, adjusted for significant co-variables. Results: Among 985 patients with cancer, 22% were considered palliative; 23% of surveyed patients smoked at diagnosis; 10% continued smoking at follow-up. Most patients perceived that continued smoking and SHS exposure negatively impacted QofL (continued smoking: 83%, SHS: 82%), fatigue (83%, 79%) and OS (86%, 81%). Palliative patients were more likely to believe that SHS worsened their cancer-related fatigue (adjusted odds ratio (aOR) = 1.65, 95% CI [1.05-2.56], P = 0.03) and worsened OS (unadjusted OR = 1.92, [1.12-3.33], P= 0.02; aOR = 1.56 [0.98-2.50], P = 0.06). Yet palliative/non-palliative status was not found to be associated with perceived benefits of smoking cessation on QofL, fatigue, or OS (P > 0.10, all comparisons). Conclusions: When compared with non-palliative patients, palliative patients with cancer perceived a greater negative impact of SHS on fatigue and survival, but had similar views of continued smoking after a cancer diagnosis. We are encouraged that palliative status did not lead to patients having diluted perceptions on the negative impact of smoking on cancer outcomes. Health care providers should continue to focus on the positive impacts of smoking cessation and SHS in this setting.

10086Background: Smoking cessation is becoming an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient knowledge of the harms of...