COVID-19 Pandemic Impact on Diagnosis, Stage, and Treatment of Hepatocellular Carcinoma in the United States.

Background and Aims: The change in hepatocellular carcinoma (HCC) care continuum during the coronavirus disease 2019 (COVID-19) pandemic remains unknown at a national level in the United States. We sought to determine the impact of the pandemic on incident HCC cases, clinical characteristics, and treatment in the United States. Methods: Using the National Cancer Database, we analyzed incident HCC cases from 2010 to 2020. The incidence rate was calculated using the population data for each year from the census bureau. Joinpoint regression analysis was applied for trend analysis, and a polynomial regression model estimated the number of projected HCC cases in 2020 according to the trend of rates from 2010 to 2019. The distribution of cancer stage and treatment modality were assessed. Results: The pandemic led to a significant reduction in reported HCC cases, from 19,597 in 2019 to 16,188 in 2020. The projected number of HCC for 2020 was 19,011, corresponding to a 14.8% reduction in 2020. Extent of reduction in the number of incident HCC cases relative to estimated cases remains consistent in racial and ethnic subgroups. Despite underdiagnosis of HCC in 2020, proportion of patients with early tumor stage (30.5% for Tumour, Node, Metastasis stage 1) and curative treatment receipt (9.1% for surgical resection, 13% for ablation, 4.2% for liver transplant) for HCC remained stable in the first year of the COVID-19 pandemic. Conclusion: There was a significant reduction in HCC cases in 2020 compared to pre-COVID years. While tumor stage and proportion of patients receiving curative treatment remained stable, continued follow-up is needed to assess potential changes during subsequent years.

Baseline weight recovery and mortality risk in head and neck cancer.

BACKGROUND: As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes. METHODS: Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models. RESULTS: Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028). CONCLUSION: A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality.

Development of a Web-Based Interactive Tool for Visualizing Breast Cancer Clinical Trial Tolerability Data.

PURPOSE: Longitudinal patient tolerability data collected as part of randomized controlled trials are often summarized in a way that loses information and does not capture the treatment experience. To address this, we developed an interactive web application to empower clinicians and researchers to explore and visualize patient tolerability data. METHODS: We used adverse event (AE) data (Common Terminology Criteria for Adverse Events) and patient-reported outcomes (PROs) from the NSABP-B35 phase III clinical trial, which compared anastrozole with tamoxifen for breast cancer-free survival, to demonstrate the tools. An interactive web application was developed using R and the Shiny web application framework that generates Sankey diagrams to visualize AEs and PROs using four tools: AE Explorer, PRO Explorer, Cohort Explorer, and Custom Explorer. RESULTS: To illustrate how users can use the interactive tool, examples for each of the four applications are presented using data from the NSABP-B35 phase III trial and the NSABP-B30 trial for the Custom Explorer. In the AE and PRO explorers, users can select AEs or PROs to visualize within specified time periods and compare across treatments. In the cohort explorer, users can select a subset of patients with a specific symptom, severity, and treatment received to visualize the trajectory over time within a specified time interval. With the custom explorer, users can upload and visualize structured longitudinal toxicity and tolerability data. CONCLUSION: We have created an interactive web application and tool for clinicians and researchers to explore and visualize clinical trial tolerability data. This adaptable tool can be extended for other clinical trial data visualization and incorporated into future patient-clinician interactions regarding treatment decisions.

Impact of the Early COVID-19 Pandemic on Incidence and Outcomes of Hepatocellular Carcinoma in the United States.

INTRODUCTION: Access to hepatocellular carcinoma (HCC) surveillance and treatments were disrupted during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to characterize the impact of the pandemic on HCC incidence and mortality rates, treatment, and outcomes in the United States. METHODS: Two nationwide databases, the United States Cancer Statistics and the National Vital Statistics System, were used to investigate HCC incidence and mortality between 2001 and 2020. Trends in age-adjusted incidence rate (aIR) and adjusted mortality rate (aMR) were assessed using joinpoint analysis. The 2020 aIR and aMR were projected based on the prepandemic data and compared with actual values to assess the extent of underdiagnosis. We assessed differences in HCC characteristics, treatment, and overall survival between 2020 and 2018-2019. RESULTS: The aIR of HCC in 2020 was significantly reduced compared with 2019 (5.22 vs 6.03/100K person-years [PY]), representing a 12.2% decrease compared with the predicted aIR in 2020 (5.94/100K PY). The greatest extent of underdiagnosis was observed in Black (-14.87%) and Hispanic (-14.51%) individuals and those with localized HCC (-15.12%). Individuals staged as regional or distant HCC were also less likely to receive treatment in 2020. However, there was no significant difference in short-term overall survival in 2020 compared with 2018-2019, with HCC mortality rates remaining stable (aMR: 2.76 vs 2.73/100K PY in 2020 vs 2019). DISCUSSION: The COVID-19 pandemic resulted in underdiagnosis of HCC, particularly early stage disease and racial ethnic minorities, and underuse of HCC-directed treatment. Longer follow-up is needed to determine the impact of the COVID-19 pandemic on HCC-related mortality.

Patient perceptions underlying ctDNA molecular surveillance for HPV(+) oropharyngeal squamous cell carcinoma.

OBJECTIVE: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). METHODS: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. RESULTS: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. CONCLUSION: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.

Patient Perceptions of Standardized Risk Language Used in ACR Prostate MRI PI-RADS Scores.

INTRODUCTION: Prostate MRI reports use standardized language to describe risk of clinically significant prostate cancer (csPCa) from "equivocal" (Prostate Imaging Reporting and Data System [PI-RADS] 3), "likely" (PI-RADS 4), to "highly likely" (PI-RADS 5). These terms correspond to risks of 11%, 37%, and 70% according to American Urological Association guidelines, respectively. We assessed how men perceive risk associated with standardized PI-RADS language. METHODOLOGY: We conducted a crowdsourced survey of 1,204 men matching a US prostate cancer demographic. We queried participants' risk perception associated with standardized PI-RADS language across increasing contexts: words only, PI-RADS sentence, full report, and full report with numeric estimate. Median perceived risk (interquartile range) and absolute under/overestimation compared with American Urological Association standards were reported. Multivariable linear mixed-effects analysis identified factors associated with accuracy of risk perception. RESULTS: Median perceived risks of csPCa (interquartile range) for the word-only context were "equivocal" 50% (50%-74%), "likely" 75% (68%-85%), and "highly likely" 87% (78%-92%), corresponding to +39%, +38%, and +17% overestimation, respectively. Median perceived risks for the PI-RADS-sentence context were 50% (50%-50%), 75% (68%-81%), and 90% (80%-94%) for PI-RADS 3, 4, and 5, corresponding to +39%, +38%, and +20% overestimation, respectively. Median perceived risks for the full-report context were 50% (35%-70%), 72% (50%-80%), and 84% (54%-91%) for PI-RADS 3, 4, and 5, corresponding to +39%, +35%, and +14% overestimation, respectively. For the full-report-with-numeric-estimate context describing a PI-RADS 4 lesion, median perceived risk was 70% (50%-%80), corresponding to +33% overestimation. Including numeric estimates increased correct perception of risk from 3% to 11% (P < .001), driven by men with higher numeracy (odds ratio 1.24, P = .04). CONCLUSION: Men overestimate risk of csPCa associated with standardized PI-RADS language regardless of context, especially for PI-RADS 3 and 4 lesions. Changes to PI-RADS language or data-sharing policies for imaging reports should be considered.

Variation in content discussed by specialty in consultations for clinically localized prostate cancer.

INTRODUCTION: Multidisciplinary consultations improve decisional conflict and guideline-concordant treatment for men with prostate cancer (PC), but differences in the content discussed by specialty during consultations are unknown. METHODS: We audiorecorded and transcribed 50 treatment consultations for localized PC across a multidisciplinary sample of urologists, radiation oncologists, and medical oncologists. Conversation was coded for narrative content using an open coding approach, grouping similar topics into major content areas. The number of words devoted to each content area per consult was used as a proxy for time spent. Multivariable Poisson regression calculated incidence rate ratios (IRR) for content-specific word count across specialties after adjustment for tumor risk and patient demographics. RESULTS: Coders identified 8 narrative content areas: overview of PC; medical history; baseline risk; cancer prognosis; competing risks; treatment options; physician recommendations; and shared decision making (SDM). In multivariable models, specialties significantly differed in proportion of time spent on treatment options, SDM, competing risks, and cancer prognosis. Urologists spent 1.8-fold more time discussing cancer prognosis than medical oncologists (IRR1.80, 95%CI:1.14-2.83) and radiation oncologists (IRR1.84, 95%CI:1.10-3.07). Urologists (IRR11.38, 95%CI:6.62-19.56) and medical oncologists (IRR10.60, 95%CI:6.01-18.72) spent over 10-fold more time discussing competing risks than radiation oncologists. Medical oncologists (IRR2.60, 95%CI:1.65-4.10) and radiation oncologists (IRR1.77, 95%CI:1.06-2.95) spent 2.6- and 1.8-fold more time on SDM than urologists, respectively. CONCLUSIONS: Specialists focus on different content in PC consultations. Our results suggest that urologists should spend more time on SDM and radiation oncologists on competing risks. Our results also highlight the importance of medical oncologists in facilitating SDM.

Contemporary risk of biochemical recurrence after radical prostatectomy in the active surveillance era.

OBJECTIVES: To assess whether contemporary risks of biochemical recurrence (BCR) after radical prostatectomy (RP) in the AS era differ from historical estimates due to changes in tumor risk case mix and improvements in risk stratification. MATERIALS AND METHODS: We sampled 6,682 men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and within tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between era and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: About 3,492 (52%) and 3,190 (48%) men underwent RP before and after 2010, respectively. In a limited multivariable model excluding tumor risk, overall BCR risk was higher post-2010 vs. pre-2010 (HR: 1.15, 95%CI: 1.05-1.25; 40% vs 36% at 8 years post-RP). However, this effect was eliminated after correcting for tumor risk (HR: 0.95, 95%CI: 0.87-1.04), suggesting that differences in tumor risk between eras mediated the change. Yet, within tumor-risk subgroups, BCR risk was significantly lower for favorable intermediate-risk (HR: 0.76, 95%CI:0.60-0.96) and unfavorable intermediate-risk PC (HR: 0.78, 95%CI: 0.67-0.90), but significantly higher for high-risk PC (HR: 1.22, 95%CI: 1.07-1.38) in the post-2010 era. 8-year risks of BCR in the post-2010 era were 21% (95%CI: 16%-25%), 25% (95%CI: 20%-30%), 41% (95%CI: 37%-46%), and 60% (95%CI: 56%-64%) for low-, FIR-, UIR-, and high-risk disease, respectively. Limitations include limited long-term follow-up in the post-2010 subgroup. CONCLUSIONS: Overall BCR risk has increased in the AS era, driven by a higher risk case mix and increased BCR risk among high-risk patients. Physicians should quote contemporary estimates of BCR when counseling patients.

Use of Persuasive Language in Communication of Risk during Prostate Cancer Treatment Consultations.

BACKGROUND: Physician treatment preference may influence how risks are communicated in prostate cancer consultations. We identified persuasive language used when describing cancer prognosis, life expectancy, and side effects in relation to a physician's recommendation for aggressive (surgery/radiation) or nonaggressive (active surveillance/watchful waiting) treatment. METHODS: A qualitative analysis was performed on transcribed treatment consultations of 40 men with low- and intermediate-risk prostate cancer across 10 multidisciplinary providers. Quotes pertaining to cancer prognosis, life expectancy, and side effects were randomized. Coders predicted physician treatment recommendations from isolated blinded quotes. Testing characteristics of consensus predictions against the physician's treatment recommendation were reported. Coders then identified persuasive strategies favoring aggressive/nonaggressive treatment for each quote. Frequencies of persuasive strategies favoring aggressive/nonaggressive treatment were reported. Logistic regression quantified associations between persuasive strategies and physician treatment recommendations. RESULTS: A total of 496 quotes about cancer prognosis (n = 127), life expectancy (n = 51), and side effects (n = 318) were identified. The accuracy of predicting treatment recommendation based on individual quotes containing persuasive language (n = 256/496, 52%) was 91%. When favoring aggressive treatment, persuasive language downplayed side effect risks and amplified cancer risk (recurrence, progression, or mortality). Significant predictors (P < 0.05) of aggressive treatment recommendation included favorable side effect interpretation, downplaying side effects, and long time horizon for cancer risk due to longevity. When favoring nonaggressive treatment, persuasive language amplified side effect risks and downplayed cancer risk. Significant predictors of nonaggressive treatment recommendation included unfavorable side effect interpretation, favorable interpretation of cancer risk, and short time horizon for cancer risk due to longevity. CONCLUSIONS: Physicians use persuasive language favoring their preferred treatment, regardless of whether their recommendation is appropriate. IMPLICATIONS: Clinicians should quantify risk so patients can judge potential harm without solely relying on persuasive language. HIGHLIGHTS: Physicians use persuasive language favoring their treatment recommendation when communicating risks of prostate cancer treatment, which may influence a patient's treatment choice.Coders predicted physician treatment recommendations based on isolated, randomized quotes about cancer prognosis, life expectancy, and side effects with 91% accuracy.Qualitative analysis revealed that when favoring nonaggressive treatment, physicians used persuasive language that amplified side effect risks and downplayed cancer risk. When favoring aggressive treatment, physicians did the opposite.Providers should be cognizant of using persuasive strategies and aim to provide quantified assessments of risk that are jointly interpreted with the patient so that patients can make evidence-based conclusions regarding risks without solely relying on persuasive language.

Variation in communication of side effects in prostate cancer treatment consultations.

BACKGROUND: Effective communication of treatment side effects (SE) is critical for shared decision-making (SDM) in localized prostate cancer. We sought to qualitatively characterize how physicians communicate SE in consultations. METHODS: We transcribed 50 initial prostate cancer treatment consultations across nine multidisciplinary providers (Urologists, Radiation Oncologists, Medical Oncologists) at our tertiary referral, academic center. Coders identified quotes describing SE and used an inductive approach to establish a hierarchy for granularity of communication: (1) not mentioned, (2) name only, (3) generalization("high"), (4) average incidence without timepoint, (5) average incidence with timepoint, and (6) precision estimate. We reported the most granular mode of communication for each SE throughout the consultation overall and across specialty and tumor risk. RESULTS: Among consultations discussing surgery (n = 40), erectile dysfunction (ED) and urinary incontinence (UI) were omitted in 15% and 12%, not quantified (name only or generalization) in 47% and 30%, and noted as average incidence without timeline in 8% and 8%, respectively. In only 30% and 49% were ED and UI quantified with timeline (average incidence with timeline or precision estimate), respectively. Among consultations discussing radiation (n = 36), irritative urinary symptoms, ED, and other post-radiotherapy SE were omitted in 22%, 42%, and 64-67%, not quantified in 61%, 33%, and 23-28%, and noted as average incidence without timeline in 8%, 22%, and 6-8%, respectively. In only 3-8% were post-radiotherapy SE quantified with timeline. Specialty concordance (but not tumor risk) was associated with higher granularity of communication, though physicians frequently failed to quantify specialty-concordant SE. CONCLUSIONS: SE was often omitted, not quantified, and/or lacked a timeline in treatment consultations in our sample. Physicians should articulate, quantify, and assign a timeline for SE to optimize SDM.

Dynamic Risk Prediction of Treatment Discontinuation Using Patient-Reported Outcomes Data in the Phase III NSABP B-35 Trial.

Predicting an individual's risk of treatment discontinuation is critical for the implementation of precision chemoprevention. We developed partly conditional survival models to predict discontinuation of tamoxifen or anastrozole using patient-reported outcome (PRO) data from postmenopausal women with ductal carcinoma in situ enrolled in the NSABP B-35 clinical trial. In a secondary analysis of the NSABP B-35 clinical trial PRO data, we proposed two models for treatment discontinuation within each treatment arm (anastrozole or tamoxifen treated patients) using partly conditional Cox-type models with time-dependent covariates. A 70/30 split of the sample was used for the training and validation datasets. The predictive performance of the models was evaluated using calibration and discrimination measures based on the Brier score and AUC from time-dependent ROC curves. The predictive models stratified high-risk versus low-risk early discontinuation at a 6-month horizon. For anastrozole-treated patients, predictive factors included baseline body mass index (BMI) and longitudinal patient-reported symptoms such as insomnia, joint pain, hot flashes, headaches, gynecologic symptoms, and vaginal discharge, all collected up to 12 months [Brier score, 0.039; AUC, 0.76; 95% confidence interval (CI), 0.57-0.95]. As for tamoxifen-treated patients, predictive factors included baseline BMI, and time-dependent covariates: cognitive problems, feelings of happiness, calmness, weight problems, and pain (Brier score, 0.032; AUC, 0.78; 95% CI, 0.65-0.91). A real-time calculator based on these models was developed in Shiny to create a web-based application with a future goal to aid healthcare professionals in decision-making. PREVENTION RELEVANCE: The dynamic prediction provided by partly conditional models offers valuable insights into the treatment discontinuation risks using PRO data collected over time from clinical trial participants. This tool may benefit healthcare professionals in identifying patients at high risk of premature treatment discontinuation and support interventions to prevent potential discontinuation.

Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma.

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

Global epidemiologic patterns of oropharyngeal cancer incidence trends.

BACKGROUND: The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in oropharyngeal cancer incidence worldwide. METHODS: We analyzed cancer incidence data between 1993 and 2012 from 42 countries using the Cancer Incidence in Five Continents database volumes V through XI. Trends in oropharyngeal cancer incidence were compared with oral cavity cancers and lung squamous cell carcinomas using log-linear regression and age period-cohort modeling. RESULTS: In total, 156 567 oropharyngeal cancer, 146 693 oral cavity cancer, and 621 947 lung squamous cell carcinoma patients were included. Oropharyngeal cancer incidence increased (P < .05) in 19 and 23 countries in men and women, respectively. In countries with increasing male oropharyngeal cancer incidence, all but 1 had statistically significant decreases in lung squamous cell carcinoma incidence, and all but 2 had decreasing or nonsignificant net drifts for oral cavity cancer. Increased oropharyngeal cancer incidence was observed both in middle-aged (40-59 years) and older (≥60 years) male cohorts, with strong nonlinear birth cohort effects. In 20 countries where oropharyngeal cancer incidence increased for women and age period-cohort analysis was possible, 13 had negative or nonsignificant lung squamous cell carcinoma net drifts, including 4 countries with higher oropharyngeal cancer net drifts vs both lung squamous cell carcinoma and oral cavity cancer (P < .05 for all comparisons). CONCLUSIONS: Increasing oropharyngeal cancer incidence is seen among an expanding array of countries worldwide. In men, increased oropharyngeal cancer is extending to older age groups, likely driven by human papillomavirus-related birth cohort effects. In women, more diverse patterns were observed, suggesting a complex interplay of risks factors varying by country, including several countries where female oropharyngeal cancer increases may be driven by HPV.

Re-examining predictors of pathologic lymph node positivity in clinically node negative oral cavity cancer.

BACKGROUND: Elective lymph node dissection (ELND) is performed for many early-stage oral cavity squamous cell carcinomas (OCSCC) with clinically negative necks (cN0), often guided by depth of invasion (DOI). However, DOI is less validated in non-tongue OC sites, and often correlates with other adverse features. We sought to evaluate the utility of DOI versus other factors for independently predicting pathologic lymph node positivity (pN+) in patients with cN0 OCSCC. METHODS: Patients with cN0 OCSCC diagnosed from 2010 to 2015 undergoing primary surgery were identified in the National Cancer Data Base. RESULTS: 5060 cN0 OCSCC patients met inclusion criteria. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.27, 95% confidence interval [CI] 3.36-5.42, P < 0.001). High histologic grade also strongly predicted pN+ (OR 3.33, 95% CI 2.20-4.60, P < 0.001). DOI had no association with the likelihood of pN+ among all OCSCC patients, but was predictive among patients within the oral tongue subset (OR 2.01, 95% CI 1.08-3.73, P = 0.03 for DOI > 20 mm vs. DOI: 2.0-3.99 mm). CONCLUSION: LVI and grade are the strongest independent predictors of pN+ in cN0 OCSCC. Contrary to prior studies, DOI was not found to be a predictor of pN+ among patients with cN0 OCSCC. However, DOI was a predictor of pN+ or the oral tongue subset, albeit still less strongly than LVI or grade. These findings could potentially be used to better identify a subset of cN0 OCSCC patients who could be considered for omission of ELND in future studies.

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer.

BACKGROUND: Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. METHODS: This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. RESULTS: Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28-0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33-0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68-0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52-0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62-0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60-0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57-0.78; P<.001). CONCLUSIONS: Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

Demographic Factors Predict Risk of Lymph Node Involvement in Patients with Endometrial Adenocarcinoma.

The presence of lymph node positivity (LN+) guides adjuvant treatment for endometrial adenocarcinoma (EAC) patients, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Sociodemographic factors in addition to pathologic tumor characteristics may more accurately predict risk of LN+ in EAC patients. Patients diagnosed between 2004 and 2016 with pathologic T1-T2 EAC who had at least one lymph node sampled at the time of surgery in the National Cancer Data Base were included. Pathologic primary tumor predictors of LN+ were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN+, nomograms were generated. Among the 35,170 EAC patients included, 2864 were node positive. Using multivariable analysis, younger patient age (OR 0.98, 95% CI 0.98-0.99, p < 0.001), black versus white race (OR 1.19, 95% CI 1.01-1.40, p = 0.04), increasing pathologic tumor stage and grade, increase in tumor size, and presence of lymphovascular invasion were predictive of regional LN+. Both black versus white (OR 1.64, 95% CI 1.27-2.09, p < 0.001) and other versus white race (OR 1.54, 95% CI 1.12-2.07, p = 0.006) strongly predicted paraaortic LN+ in the multivariable analysis. Independent subset analyses of black and white women revealed that tumor grade was a stronger predictor of LN+ among black women. In addition to standard pathologic tumor features, patient age and race were associated with a higher risk of regional LN+ generally and paraaortic LN+ specifically. This information may inform adjuvant treatment decisions and guide future studies.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

BACKGROUND: The comparative impact of histologic variants and grade has not been well described. METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

Activin and BMP Signalling in Human Testicular Cancer Cell Lines, and a Role for the Nucleocytoplasmic Transport Protein Importin-5 in Their Crosstalk.

Testicular germ cell tumours (TGCTs) are the most common malignancy in young men. Originating from foetal testicular germ cells that fail to differentiate correctly, TGCTs appear after puberty as germ cell neoplasia in situ cells that transform through unknown mechanisms into distinct seminoma and non-seminoma tumour types. A balance between activin and BMP signalling may influence TGCT emergence and progression, and we investigated this using human cell line models of seminoma (TCam-2) and non-seminoma (NT2/D1). Activin A- and BMP4-regulated transcripts measured at 6 h post-treatment by RNA-sequencing revealed fewer altered transcripts in TCam-2 cells but a greater responsiveness to activin A, while BMP4 altered more transcripts in NT2/D1 cells. Activin significantly elevated transcripts linked to pluripotency, cancer, TGF-ß, Notch, p53, and Hippo signalling in both lines, whereas BMP4 altered TGF-ß, pluripotency, Hippo and Wnt signalling components. Dose-dependent antagonism of BMP4 signalling by activin A in TCam-2 cells demonstrated signalling crosstalk between these two TGF-ß superfamily arms. Levels of the nuclear transport protein, IPO5, implicated in BMP4 and WNT signalling, are highly regulated in the foetal mouse germline. IPO5 knockdown in TCam-2 cells using siRNA blunted BMP4-induced transcript changes, indicating that IPO5 levels could determine TGF-ß signalling pathway outcomes in TGCTs.

Concurrent prognostic utility of lymph node count and lymph node density for men with pathological node-positive prostate cancer.

BACKGROUND: While both the number (+LN) and density (LND) of metastatic lymph nodes on radical prostatectomy lymphadenectomy predict mortality in prostate cancer, the independent impact of each on overall mortality (OM) is unknown. METHODS: We sampled men who underwent radical prostatectomy and lymphadenectomy between 2004 and 2013 from the National Cancer Database. Multivariable Cox proportional hazards analysis with restricted cubic spline was used to assess the non-linear association of +LN count and LND with OM. RESULTS: Of 229,547 men in our sample, 3% (n = 7507) had +LNs, of which 89% had 1-3 +LN and 11% had ≥4 +LN. In multivariable Cox analysis across all patients, OM increased with each additional +LN up to four (HR 1.14, 95%CI 1.06-1.23 per node), with no increase beyond 4 +LN. LND was an independent predictor of OM (HR 1.09, 95%CI 1.06-1.12 per 10% increase). However, after excluding patients with inadequate nodal sampling (<5 LN examined), the variation in OM explained by LND was negligible for patients with ≤3 +LN. In men with 1, 2, and 3 +LN, there was a 0.28%, 0.02%, and 0.50% increase in OM for each 10% increase in LND, compared with 1.9% and 1.6% for men with 4 or 5+ LNs. CONCLUSIONS: While +LN count and LND independently predict OM, the impact of LND is negligible in men with ≤3 +LN, who comprise the vast majority of men with +LN. Pathological nodal staging should primarily rely on LN count rather than LND.