Short- and long-term outcomes of robotic versus open radical antegrade modular pancreatosplenectomy: a retrospective propensity score-matched cohort study.

BACKGROUND: Robotic distal pancreatectomy has increasingly been accepted as it has overcome some of the limitations of open distal pancreatectomy, whilst the outcomes following robotic radical antegrade modular pancreatosplenectomy (RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of robotic RAMPS and open RAMPS for PDAC. METHODS: The patients who underwent robotic RAMPS and open RAMPS for PDAC at our clinical centre between January 2017 and December 2021 were reviewed. After a propensity score matching (PSM) at a 1:1 ratio, the perioperative and pathological outcomes in the both groups were reviewed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: 318 cases were recorded in robotic and open groups. The robotic group showed advantages in operative time [205.00 (166.00, 240.00) min vs 235 (184.75, 270.00) min, P = 0.002], estimated blood loss [100 (50, 100) ml vs 300 (100, 400) ml, P < 0.001], delayed gastric emptying [0 vs 5.03%, P = 0.007] and postoperative hospital stay [7.00 (5.00, 10.00) days vs 11.00 (8.00, 14.00) days, P < 0.001]. There were no significant differences in rate of severe postoperative complications between the robotic group and the open group. Multivariable analysis showed that carbohydrate antigen 19-9, estimated blood loss, N stage, tumour differentiation, chemotherapy and vascular invasion were independent risk factors for OS and RFS of these patients. CONCLUSIONS: Robotic RAMPS was safe and had some advantages over open RAMPS for PDAC. There were no significantly differences in oncological outcomes and long-term survival rates between the robotic and open groups. Robotic RAMPS expanded the indications for minimally invasive surgeries for PDAC to a certain extent.

Awareness of the Harms of Continued Smoking Among Cancer Survivors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Benchmarking strategies for cross-species integration of single-cell RNA sequencing data.

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. Here, we benchmark 28 combinations of gene homology mapping methods and data integration algorithms in a variety of biological settings. We examine 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 develop a new biology conservation metric to address the maintenance of cell type distinguishability. Overall, scANVI, scVI and SeuratV4 methods achieve a balance between species-mixing and biology conservation. For evolutionarily distant species, including in-paralogs is beneficial. SAMap outperforms when integrating whole-body atlases between species with challenging gene homology annotation. We provide our freely available cross-species integration and assessment pipeline to help analyse new data and develop new algorithms.

SelectBCM tool: a batch evaluation framework to select the most appropriate batch-correction methods for bulk transcriptome analysis.

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.

Dissolved and particulate heavy metal pollution status in seawater and sedimentary heavy metals of the Bohai Bay.

Heavy metal contamination has been the focus of many studies owing to its potential risk on the health of coastal ecosystems. The Bohai Bay (BHB) is the second largest bay of Bohai Sea and subjected to serious anthropogenic perturbations. The aim of this study was to evaluate the distribution and pollution status of toxic heavy metals in seawater with two fractions (dissolved and suspended particulate phases) and surface sediments of this coastal system. Therefore, several hydrochemical parameters and concentration of seawater metals and sediment metals were measured at two cruises of 2020 summer and autumn. The spatial distribution and potential ecological risks were examined and their inter-element relationships were analyzed to identify potential geochemical processes. By comparing historical data since 1978, we find declining trends in contents of most trace metals in seawater and sediments, suggesting that recent pollution control in BHB have an effect on diminishing metal pollution. Dissolved metals showed no significant dependence on their particulate phase. The seawater posed a moderate to high level of ecological risk. The hydrochemical factors mainly had a greater impact on dissolved metals during summer, whereas they influenced suspended metals more significantly during autumn. These results provide fundamental information to support environmental quality management and ecological protection in coastal systems.

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy.

OBJECTIVE: To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAFV600 wild-type melanoma who had progressed on prior anti‒programmed death-1 (PD-1) therapy. PATIENTS AND METHODS: This 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. RESULTS: 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. CONCLUSIONS: Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAFV600 wild-type melanoma with disease progression on or after prior anti‒PD-1 therapy demonstrated limited activity. CLINICAL TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov; NCT03178851.

Water quality shifts the dominant phytoplankton group from diatoms to dinoflagellates in the coastal ecosystem of the Bohai Bay.

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.

Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis: A preliminary experience with 26 patients.

BACKGROUND: Preoperative diagnosis rate of pancreatic cancer has increased year by year. The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor, and there is no effective and unified treatment strategy. AIM: To evaluate the therapeutic effect of radioactive 125I seed implantation for pancreatic cancer patients with unexpected liver metastasis. METHODS: The demographics and perioperative outcomes of patients who underwent 125I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1, 2017 and June 1, 2019 were retrospectively analyzed. During the operation, 125I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment. RESULTS: Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis. There were 26 patients in this study, including 18 males and 8 females, aged 60.5 ± 9.7 years. The most common tumor site was the pancreatic head (17, 65.4%), followed by the pancreatic neck and body (6, 23.2%) and pancreatic tail (3, 11.4%). Fourteen patients (53.8%) underwent palliative surgery and postoperative pain relief occurred in 22 patients (84.6%). The estimated blood loss in operation was 148.3 ± 282.1 mL and one patient received blood transfusion. The postoperative hospital stay was 7.6 ± 2.8 d. One patient had biliary fistula, one had pancreatic fistula, and all recovered after conservative treatment. After operation, 7 patients received chemotherapy and 19 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (68.6% vs 15.8%, P = 0.012). The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo, respectively (χ 2 = 7.083, P = 0.008). CONCLUSION: Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.

Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome.

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.

Robotic resection of duodenal gastrointestinal stromal tumour: Preliminary experience from a single centre.

BACKGROUND: Experience in minimally invasive surgery in the treatment of duodenal gastrointestinal stromal tumors (DGISTs) is accumulating, but there is no consensus on the choice of surgical method. AIM: To summarize the technique and feasibility of robotic resection of DGISTs. METHODS: The perioperative and demographic outcomes of a consecutive series of patients who underwent robotic resection and open resection of DGISTs between May 1, 2010 and May 1, 2020 were retrospectively analyzed. The patients were divided into the open surgery group and the robotic surgery group. Pancreatoduodenectomy (PD) or limited resection was performed based on the location of the tumour and the distance between the tumour and duodenal papilla. Age, sex, tumour location, tumour size, operation time (OT), estimated blood loss (EBL), postoperative hospital stay (PHS), tumour mitosis, postoperative risk classification, postoperative recurrence and recurrence-free survival were compared between the two groups. RESULTS: Of the 28 patients included, 19 were male and 9 were female aged 51.3 ± 13.1 years. Limited resection was performed in 17 patients, and PD was performed in 11 patients. Eleven patients underwent open surgery, and 17 patients underwent robotic surgery. Two patients in the robotic surgery group underwent conversion to open surgery. All the tumours were R0 resected, and there was no significant difference in age, sex, tumour size, operation mode, PHS, tumour mitosis, incidence of postoperative complications, risk classification, postoperative targeted drug therapy or postoperative recurrence between the two groups (P > 0.05). OT and EBL in the robotic group were significantly different to those in the open surgery group (P < 0.05). All the patients survived during the follow-up period, and 4 patients had recurrence and metastasis. No significant difference in recurrence-free survival was noted between the open surgery group and the robotic surgery group (P > 0.05). CONCLUSION: Robotic resection is safe and feasible for patients with DGISTs, and its therapeutic effect is equivalent to open surgery.

Effect of Itraconazole, a Potent CYP3A4 Inhibitor, on the Steady-State Pharmacokinetics of Vemurafenib in Patients With BRAFV600 Mutation-Positive Malignancies.

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.

Radioactive 125I seed implantation for locally advanced pancreatic cancer: A retrospective analysis of 50 cases.

BACKGROUND: Pancreatic cancer is one of the common malignant tumors of the digestive system, and radical resection is the first choice of treatment for pancreatic cancer. If patients with locally advanced pancreatic cancer cannot be treated in time and effectively, their disease often develops rapidly and their survival period is very short. AIM: To evaluate the therapeutic effect of 125I seed implantation in patients with locally advanced pancreatic cancer. METHODS: The demographics and perioperative outcomes of a consecutive series of patients who underwent 125I seed implantation to treat locally advanced pancreatic cancer between January 1, 2017 and June 30, 2019 were retrospectively analyzed. According to the results of preoperative computed tomography or magnetic resonance imaging, the treatment planning system was used to determine the area and number of 125I seeds implanted. During the operation, 125I seeds were implanted into the tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment. RESULTS: Among the 50 patients, there were 29 males and 21 females, with a mean age of 56.9 ± 9.8 years. The main reason for the failure of radical resection was superior mesenteric artery invasion (37, 74%), followed by superior mesenteric vein invasion (33, 66%). Twenty-one (62%) patients underwent palliative surgery and postoperative pain relief occurred in 40 (80%) patients. The estimated blood loss in operation was 107.4 ± 115.3 mL and none of the patient received blood transfusion. The postoperative hospital stay was 7.5 ± 4.2 d; one patient had biliary fistula and three had pancreatic fistula, all of whom recovered after conservative treatment. After operation, 26 patients received chemotherapy and 24 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (60.7% vs 35.9%, P = 0.034). The mean overall survival of patients of the chemotherapy group and non-chemotherapy group was 14 and 11 mo, respectively (χ 2 = 3.970, P = 0.046). CONCLUSION: Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time, relieve pain, and improve the quality of life of patients with locally advanced pancreatic cancer.

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China.

BACKGROUND: Nab-paclitaxel plus gemcitabine (AG) has resulted in higher tumor response and survival rates for metastatic or advanced pancreatic ductal adenocarcinoma (PDAC) compared with gemcitabine (GEM) alone. AIM: To examine the feasibility and safety of AG adjuvant chemotherapy of resectable PDAC. METHODS: We retrospectively analyzed patients with resected PDAC who received AG or GEM as postoperative adjuvant treatment between January 2013 and December 2016 at the Chinese People's Liberation Army General Hospital, Beijing, China. The patients adopted combined nab-paclitaxel (125 mg/m2) and GEM (1 g/m2) or GEM (1 g/m2) alone treatment, on days 1 and 8 every 3 wk for six cycles, unless intolerable adverse events or disease progression occurred. The disease-free survival, overall survival (OS) and adverse events of the two groups were statistically analyzed. RESULTS: Compared with GEM, median disease-free survival (12.2 mo vs 15.8 mo, P = 0.039) and OS (20.6 mo vs 28.3 mo, P = 0.028) were significantly improved in the AG group. The 2-year OS rates were 63.3% and 43.3% in the AG and GEM groups, respectively. However, the incidence of sensory neuropathy was increased significantly in the AG than the GEM group (53.3% vs 23.3%, P < 0.001). CONCLUSION: In our initial experience, AG significantly improved disease-free survival and OS of patients with resected PDAC. AG may be a potential option for postoperative adjuvant chemotherapy of resectable PDAC.

Correction: Hedgehog inhibition mediates radiation sensitivity in mouse xenograft models of human esophageal adenocarcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0194809.].

Computer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray.

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 < 0.001). Within this OTSCC cohort, smokers had significantly stronger PD-L1 stain intensity and higher numbers of CD3+, CD4+ and FOXP3+ TILs. In the subset of patients who had received adjuvant radiotherapy, a higher number of CD8+ TILs was associated with inferior OS and DFS. Taken together, this proof-of-principle study demonstrates the robustness and utility of computer-assisted image analysis for high-throughput assessment of multiple IHC markers on TMAs, with potential implications for studies on prognostic and predictive biomarkers.

Hedgehog inhibition mediates radiation sensitivity in mouse xenograft models of human esophageal adenocarcinoma.

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.

Perceptions of Continued Smoking and Smoking Cessation Among Patients With Cancer.

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.

Impact of Type 2 Diabetes Mellitus on Survival in Head and Neck Squamous Cell Carcinoma.

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.

Body mass index and prognosis in patients with head and neck cancer.

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 < .01). 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.

Exploring the Impact of Human Papillomavirus Status, Comorbidity, Polypharmacy, and Treatment Intensity on Outcome of Elderly Oropharyngeal Cancer Patients Treated With Radiation Therapy With or Without Chemotherapy.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.