Risk Of Cancer-related Death Research Articles

Anthropometrics and cancer prognosis: a multicenter cohort study

BackgroundAnthropometric indicators have been shown to be associated with the prognosis of patients with cancer. However, any single anthropometric index has limitation in predicting the prognosis. ObjectivesThis study aimed to observe the predictive role of 7 anthropometric indicators based on body size on the prognosis of patients with cancer. MethodsA principal component analysis (PCA) on 7 anthropometric measurements: height, weight, BMI, hand grip strength (HGS), triceps skinfold thickness (TSF), mid–upper arm circumference (MAC), and calf circumference (CAC) was conducted. Principal components (PCs) were derived from this analysis. Cox regression analysis was used to investigate the association between the prognosis of patients with cancer and the PCs. Subgroups and sensitivity analyses were also conducted. ResultsThrough PCA, 4 distinct PCs were identified, collectively explaining 88.3% of the variance. PC1, primarily characterized by general obesity, exhibited a significant inverse association with risk of cancer-related death (adjusted hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.83, 0.88). PC2 (short stature with high TSF) was not significantly associated with cancer prognosis. PC3 (high BMI coupled with low HGS) demonstrated a significant increase with risk of cancer-related death (adjusted HR: 1.08; 95% CI: 1.05, 1.11). PC4 (tall stature with high TSF) exhibited a significant association with increased cancer risk (adjusted HR: 1.05; 95% CI: 1.02, 1.07). These associations varied across different cancer stages. The stability of the results was confirmed through sensitivity analyses. ConclusionsDifferent body sizes are associated with distinct prognostic outcomes in patients with cancer. The impact of BMI on prognosis is influenced by both HGS and subcutaneous fat. This finding may influence the clinical care of cancer and improve the survival of cancer patients.

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis.

Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk. We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs. We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47). LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations. CRD42021271658.

Causes of death after first time venous thromboembolism

BackgroundCauses of death after first time community-acquired venous thromboembolism (VTE) diagnosed in unselected patients at the emergency department (ED) was investigated.Materials and methodsThe study consists of all patients > 18 years of age who had a visit for any medical reason to any of 5 different ED in Stockholm County, Sweden from 1st January 2016 to 31st December 2017. We have identified all patients with a first registered incident VTE; deep vein thrombosis (DVT) and/or pulmonary embolism (PE) during the study period. Cox regression models were used to estimate hazards ratios (HR) with 95% confidence intervals (CIs) for all-cause mortality and cause-specific death in patients with DVT or PE using all other patients as the reference group.ResultsIn total, 359,884 patients had an ED visit during the study period of whom about 2.1% were diagnosed with VTE (DVT = 4,384, PE = 3,212). The patients with VTE were older compared to the control group. During a mean follow up of 2.1 years, 1567 (21%) and 23,741(6.7%) patients died within the VTE and reference group, respectively. The adjusted risk of all-cause mortality was nearly double in patients with DVT (HR 1.7; 95% CI, 1.5–1.8) and more than 3-fold in patients with PE (HR 3.4; 95% CI, 3.1–3.6). While the risk of cancer related death was nearly 3-fold in patient with DVT (HR 2.7; 95% CI, 2.4–3.1), and 5-fold in PE (HR 5.4; 95% CI, 4.9-6.0 respectively). The diagnosis of PE during the ED visit was associated with a significantly higher risk of cardiovascular death (HR 2.2; 95% CI, 1.9–2.6).ConclusionPatients with VTE have an elevated risk of all-cause mortality, including cardiovascular death.

Impact of Deployment on Survival in Military Personnel with Non-Hodgkin Lymphoma

Introduction: It is estimated that approximately 3.5 million active duty service members (ADSM) have deployed to Afghanistan and Iraq from 2001-2022. There has been concern about potential exposure to carcinogenic or environmental hazards during overseas deployment. A recent study found ADSM with no prior deployments had an increased risk of cancer mortality compared to those who had served in Operation Iraqi Freedom/Operation Enduring Freedom. Moreover, Nordic personnel with military deployments were also found to have a lower risk of cancer related death when compared to the general population. While there may be a link between potential environmental exposures, there is a lack of data on non-Hodgkin lymphoma (NHL) survival in servicemembers who have previously deployed. Additionally, there are no studies comparing risk of aggressive B-cell lymphoma in these patient populations. Methods: Documented cases of NHL in the DoD's Tumor Registry (Oncolog) from 2001-2022 were obtained. This information was compared to the Defense Manpower Data Center's deployment data and the two datasets were merged. ADSMs and retirees were included; dependents were excluded. A multivariable logistic regression analysis was done to assess the impact of prior deployment on cancer survival in NHL, accounting for age, race, cancer stage, ethnicity, and gender. Results: There were 2,295 servicemembers and retirees diagnosed with NHL from 2001-2022. About 20% had previously deployed (n=467). Median age at diagnosis in those who had deployed was 35 years compared to 54 years for non-deployed (p<0.001). Race, ethnicity, and gender were similar between both arms. Multivariable logistic regression analysis demonstrated prior deployment was associated with better survival after accounting for age, race, stage, ethnicity, and gender (OR 0.63, 95% CI 0.40-0.97, p=0.037). In addition to deployment status, other variables that influenced survival were age (OR 1.04, 95% CI 1.03-1.54, p<0.001), stage (OR 2.92 for stage IV vs. stage I, 95% CI 2.06-4.15, p<0.001), and race (OR 1.97 for black vs. white race, 95% CI 1.37-2.83, p<0.001). To assess whether NHL subtype played a role in these findings, a post-hoc analysis was performed on patients with B-cell NHLs, revealing that ADSM with prior deployment were equally likely to have indolent and aggressive subtypes of B-cell NHL as ADSM who had never deployed. Among personnel with prior deployment, 29.6% and 70.4% had indolent and aggressive B-cell NHLs respectively, compared to 32.9% and 67.1% amongst those who never deployed (p=0.25). Conclusions: Military personnel with NHL who had previously deployed lived longer than those with no prior deployment, even after adjusting for age differences between the two cohorts. These findings are not attributable to B-cell NHL subtype (i.e. deployed personnel did not have more indolent NHLs than non-deployed personnel). These results highlight the healthy deployer effect, in which ADSM who are deployable are required to meet minimum fitness standards, undergo a physical health assessment, and do not have disqualifying comorbidities. This study did not evaluate whether an overseas deployment is associated with an increased risk of NHL, but it does appear to provide evidence that potential deployment-related exposures do not appear to alter the biology or subtype of B-cell NHLs. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.

Metastasis-Directed Therapy for Metachronous Lung Metastases in Prostate Cancer

Introduction: As interest in metastasis-directed therapy (MDT) for prostate cancer (PCa) grows, exploring indications and patient selection is increasingly more important. Thus far, few studies have described long-term outcomes after surgical MDT in those with disease recurrence involving the lung. The objective of our study was to compare the cumulative incidence of cancer-related death by treatment modality in men with metachronous pulmonary metastases from PCa. Methods: In a single-institution retrospective study, we identified 75 men from the prospectively maintained Mayo Clinic C-11 Positron Emission Tomography Choline PCa registry with recurrent prostate cancer involving the lung but no other visceral organs. Patients were categorized into 3 groups based on treatment modalities: wedge resection ± hormonal therapy, chemohormonal therapy, and hormonal therapy alone. The risk of cancer-related death after treatment at the time of lung metastases was reported as cumulative incidence estimates. Non–cancer-related deaths were treated as a competing risk of death. A univariate Cox regression model was conducted to assess the impact of treatment modality on the risk of cancer-related death. Results: At the time of lung metastasis, the median age was 69.5 years, and the median (IQR) prostate-specific antigen was 4 (1.3-8.6) ng/ml. Forty-seven patients (62.7%) had hormone-sensitive disease, and 28 patients (37.3%) had hormone-resistant disease. A total of 26 patients (34.7%) were treated with wedge resection ± hormonal therapy, 27 (36%) with chemohormonal therapy, and 22 (29.3%) with hormonal therapy alone. The median (IQR) follow-up time was 50.3 (31.1-78.4) months, and 21 patients (28%) died. Patients who were treated with wedge resection ± hormonal therapy had lower rated of cancer-related death compared with those who received chemohormonal therapy (Hazard Ratio [HR]: 4.14, 95% CI: 1.01-16.96, P = .048) or hormonal therapy alone (HR: 6.37, 95% CI: 1.72-23.54, P = .005). Conclusion: This exploratory analysis supports the safety and feasibility of surgical metastasis-directed therapy in select patients with recurrent prostate cancer involving the lung. Favorable long-term survival provides justification for further evaluation of this approach.

Racial and Ethnic Disparities in Survival Among People With Second Primary Cancer in the US

Comprehensive data for racial and ethnic disparities after second primary cancers (SPCs) are lacking despite the growing burden of SPCs. To quantify racial and ethnic disparities in survival among persons with SPCs. This population-based, retrospective cohort study used data from 18 Surveillance, Epidemiology, and End Results registries in the US for persons diagnosed with the most common SPCs at age 20 years or older from January 1, 2000, to December 31, 2013 (with follow-up through December 31, 2018). Data were analyzed between January and April 2023. Race and ethnicity (Hispanic, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, and non-Hispanic White). The main outcomes were 5-year relative survival and cause-specific survival. Cause-specific hazard ratios (HRs) were calculated for death from cancer or cardiovascular disease (CVD) in each racial and ethnic minority population compared with the White population overall and stratified by SPC type, with adjustment for sex, year and age at SPC diagnosis, and prior cancer type and stage (baseline model) and additionally for county attributes (household income, urbanicity), SPC characteristics (stage, subtype), and treatment. Among 230 370 persons with SPCs (58.4% male), 4.5% were Asian or Pacific Islander, 9.6% were Black, 6.4% were Hispanic, and 79.5% were White. A total of 109 757 cancer-related deaths (47.6%) and 18 283 CVD-related deaths (7.9%) occurred during a median follow-up of 54 months (IQR, 12-93 months). In baseline models, compared with the White population, the risk of cancer-related death overall was higher in the Black (HR, 1.21; 95% CI, 1.18-1.23) and Hispanic (HR, 1.10; 95% CI, 1.07-1.13) populations but lower in the Asian or Pacific Islander population (HR, 0.93; 95% CI, 0.90-0.96). When stratified by 13 SPC types, the risk of cancer-related death was higher for 10 SPCs in the Black population, with the highest HR for uterine cancer (HR, 1.87; 95% CI, 1.63-2.15), and for 7 SPCs in the Hispanic population, most notably for melanoma (HR, 1.46; 95% CI, 1.21-1.76). For CVD-related death, the overall HR was higher in the Black population (HR, 1.41; 95% CI, 1.34-1.49), with elevated risks evident for 11 SPCs, but lower in the Asian or Pacific Islander (HR, 0.75; 95% CI, 0.69-0.81) and Hispanic (HR, 0.90; 95% CI, 0.84-0.96) populations than in the White population. After further adjustments for county attributes and SPC characteristics and treatment, HRs were reduced for cancer-related death and for CVD-related death and associations in the same direction remained. In this cohort study of SPC survivors, the Black population had the highest risk of both death from cancer and death from CVD, and the Hispanic population had a higher risk of death from cancer than the White population. Attenuations in HRs after adjustment for potentially modifiable factors highlight opportunities to reduce survival disparities among persons with multiple primary cancers.

Expression of c-MET in Estrogen Receptor Positive and HER2 Negative Resected Breast Cancer Correlated with a Poor Prognosis.

Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14−54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with high c-MET tumor had significantly worse (p = 0.00026) and BCSS (p = 0.0013). Univariate analysis showed a significant association between large tumor size, elevated Ki67, c-MET values and increased risk of recurrence or death. The multivariate COX regression model showed that tumor size and high c-MET expression were independent predictors of DFS (p = 0.019 and p = 0.022). Moreover, large tumor size was associated with significantly higher risk of cancer related death at multivariate analysis (p = 0.017), while a trend towards a poorer survival was registered in the high c-MET levels cohort (p = 0.084). Conclusions: In our series, high c-MET expression correlated with poor survival outcomes. Further studies are warranted to validate the clinical relevance and applicability of c-MET as a prognostic factor in ER+/HER2- early BC.

Causes of death in an unselected population with first time venous thromboembolism

Abstract Background and aim Causes of death in an unselected population with first-time community acquired venous thromboembolism (VTE) is largely unknown in the contemporary era of direct oral anticoagulation (DOAC). Material and methods All patients &amp;gt;18 years of age who had a visit for any medical reason to any of 5 different emergency departments (EDs) in our city from 1st January 2016 to 31st December 2017 were included. We identified all patients with any incident VTE (deep vein thrombosis (DVT) and/or pulmonary embolism (PE)) at the time of the ED visit. Cox regression models were used to estimate hazards ratios (HR) with 95% confidence intervals (CIs) for all-cause mortality and cause-specific death in patients with any VTE, using all other ED patients as the reference group. Results In total, 409,971 patients had an ED visit during the study period, of whom 2% were diagnosed with VTE (DVT= 4,817, PE= 3,147). During a median follow up of 2.6 years, 1265 (16%) and 25,191 (6.3%) patients died within the VTE and reference group respectively. The adjusted risk of cancer related death was nearly 3-fold in patient with DVT (HR 2.7; 95% CI, 2.4–3.1), and 5-fold in PE patients (HR 4.6; 95% CI, 4.1–5.1 respectively), compared to the referent. A diagnosis of PE at the ED visit was associated with a 50% increased risk of cardiovascular death (HR 1.5; 95% CI, 1.2–1.9). Conclusion Patients with VTE have a high risk of all-cause mortality, including non-cancer related death and cardiovascular death despite improvements of diagnosis and treatment with DOAC. The study findings indicate that further improvement is needed in VTE management. Funding Acknowledgement Type of funding sources: None.

Incarceration status and cancer mortality: A population-based study.

The complex relationship between incarceration and cancer survival has not been thoroughly evaluated. We assessed whether cancer diagnosis during incarceration or the immediate post-release period is associated with higher rates of mortality compared with those never incarcerated. We conducted a population-based study using a statewide linkage of tumor registry and correctional system movement data for Connecticut adult residents diagnosed with invasive cancer from 2005 through 2016. The independent variable was place of cancer diagnosis: during incarceration, within 12 months post-release, and never incarcerated. The dependent variables were five-year cancer-related and overall survival rates. Of the 216,540 adults diagnosed with invasive cancer during the study period, 239 (0.11%) people were diagnosed during incarceration, 479 (0.22%) within 12 months following release, and the remaining were never incarcerated. After accounting for demographics and cancer characteristics, including stage of diagnosis, the risk for cancer-related death at five years was significantly higher among those diagnosed while incarcerated (AHR = 1.39, 95% CI = 1.12-1.73) and those recently released (AHR = 1.82, 95% CI = 1.57-2.10) compared to the never-incarcerated group. The risk for all-cause mortality was also higher for those diagnosed with cancer while incarcerated (AHR = 1.92, 95% CI = 1.63-2.26) and those recently released (AHR = 2.18, 95% CI = 1.94-2.45). There is a higher risk of cancer mortality among individuals diagnosed with cancer during incarceration and in the first-year post-release, which is not fully explained by stage of diagnosis. Cancer prevention and treatment efforts should target people who experience incarceration and identify why incarceration is associated with worse outcomes.

Lipidomic Profiling Identifies a Novel Lipid Signature Associated with Ethnicity-Specific Disparity of Bladder Cancer.

Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; unfortunately, this disparity in BLCA mortality remains poorly understood. In this study, we have used an ethnicity-balanced cohort for unbiased lipidomics profiling to study the changes in the lipid fingerprint for AA and EA BLCA tissues collected from similar geographical regions to determine a signature of ethnic-specific alterations. We identified 86 lipids significantly altered between self-reported AA and EA BLCA patients from Augusta University (AU) cohort. The majority of altered lipids belong to phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), ly sophosphatidylcholines (lysoPCs), phosphatidylserines (PSs), and diglycerides (DGs). Interestingly, levels of four lysoPCs (lyso PCs 20:3, lyso PCs 22:1, lyso PCs 22:2, and lyso PCs 26:1) were elevated while, in contrast, the majority of the PCs were reduced in AA BLCA. Significant alterations in long-chain monounsaturated (MonoUN) and polyunsaturated (PolyUN) lipids were also observed between AA and EA BLCA tumor tissues. These first-in-field results implicate ethnic-specific lipid alterations in BLCA.

The Effect of the Appropriate Timing of Radiotherapy on Survival Benefit in Patients with Metastatic Esophageal Cancer Who Have Undergone Resection of Primary Site: A SEER Database Analysis.

Background Metastatic esophageal cancer (MEC) is an advanced stage of esophageal cancer. However, still, resection of primary site and radiotherapy are considered treatment modalities to treat patients with MEC. Hence, this study is aimed at exploring the effect of the appropriate timing of radiotherapy on the survival benefit of these patients by comparing cancer-specific survival (CSS). Method The patient information was obtained from the National Surveillance Epidemiology and End Results (SEER) database between the years 2004 and 2017. We used the SEER∗ STAT (V8.3.9.2) software to search and download data. Patients treated with pre- and postoperative radiotherapy were divided into two groups. The propensity score matching (PSM) analysis was performed to increase the comparability of data within two groups. We used the Kaplan-Meier method to analyze and compare the CSS between the two groups. The Cox risk model was used to analyze variables affecting patient survival. Results A total of 599 patients with MEC who experienced resection of the primary site and radiotherapy were recruited. 144 pairings formed through PSM. The 5-year CSS was 23.0% and 11.7% for patients who have undergone pre- and postoperative radiotherapy, respectively. Patients who have undergone preoperative radiotherapy showed better CSS than those who received postoperative radiotherapy (P < 0.001). The multivariate Cox analysis of the entire cohort showed that age > 60 years at the time of diagnosis (HR = 1.481, 95% CI: 1.1341-1.934, and P = 0.04) and other histological types of esophageal cancer (HR = 1.581, 95% CI: 1.067-2.341, and P = 0.022) increased the risk of cancer-related death. Inversely, marriage (HR = 0.696, 95% CI: 0.514-0.942, and P = 0.019) and preoperative radiotherapy (HR = 0.664, 95% CI: 0.517-0.853, and P < 0.001) reduced the risk of death from cancer. Conclusions For patients with MEC, preoperative radiotherapy might have a significant effect on the survival benefit over those who receive postoperative radiotherapy.

Patient preferences for cancer screening in chronic kidney disease: a best-worst scaling survey.

Despite an increased cancer risk for patients with chronic kidney disease (CKD), uptake of cancer screening varies due to competing priorities and complex health-related issues. This study aimed to elicit the preferences and important attributes of cancer screening in patients with CKD. An on-line best-worst scaling survey was used to ascertain the relative importance of 22 screening attributes among CKD patients using an incomplete block design. Preference scores (0-1) were calculated by multinomial logistic regression. Preference heterogeneity was evaluated. The survey was completed by 83 patients: 26 not requiring kidney replacement therapy, 20 receiving dialysis and 37 transplant recipients (mean age 59 years, 53% men, 75% prior to cancer screening). The five most important attributes were early detection {preference score 1.0 [95% confidence interval (CI) 0.90-1.10]}, decreased risk of cancer death [0.85 (0.75-0.94)], false negatives [0.71 (0.61-0.80)], reduction in immunosuppression if detected [0.68 (0.59-0.78)] and non-invasive interventions after positive results [0.68 (0.59-0.78)]. Preference heterogeneity reflected the stage of CKD. Immunosuppression reduction [mean difference 0.11 (95% CI 0.02-0.19)] and views of family/friends [0.10 (reference attribute)] were important for transplant recipients. Screening frequency [-0.18 (95% CI -0.26 to -0.10)] and overdiagnosis of harmless cancers [-0.14 (95% CI -0.22 to -0.10)] were important for dialysis patients. Early detection, risk of cancer-related death, false negatives, immunosuppression reduction and non-invasive interventions following detection are important cancer screening considerations among CKD patients. Patient preferences are key to shared decision-making and individualized cancer screening.

Black Disparities in Targeted Therapy Clinical Trials – A Call for Future Reset

Studies show marked disparities in the relative risk of cancer death between Black Americans and White Americans even after adjusting for the stage at diagnosis and age. This may be explained by disparities in different aspects of cancer care including providing equal screening opportunities, availability of proper treatment options and inclusivity in clinical trials. To our knowledge, our study is the first descriptive study on Black disparities in targeted therapy clinical trials. We collected data on Black inclusivity from pivotal clinical trials as well as trials of special interest involving targeted therapies in some of the commonly encountered cancers. Our results show that most targeted therapy trials included in our review were multinational including some participating countries with very few or no Blacks and therefore had very poor Black representation with an average of around 1-3%. Also, some trials lacked transparent data on the racial demographics raising concerns on the generalizability of data when extrapolated to treat the Black population. We have reviewed existing literature on differences in cancer biology and host biology depending on the race and end with suggestions to improve Black inclusivity in clinical trials.

The impact of age and stage on the competing risk of cancer-related and non-cancer death in low- or high-grade endometrioid endometrial carcinoma and uterine serous carcinoma

Objectives: To estimate the impact of age and stage on the risk of cancer-related death (CRD) and non-cancer death (NCD) in women with low grade (LG)-endometrioid endometrial carcinoma (EEC) relative to high grade (HG)-EEC or uterine serous carcinoma (USC). Methods: Women diagnosed between 1988-2016 with stage I-IV LG-EEC (grade 1 or 2), HG-EEC (grade 3) or USC in the 18-region Surveillance, Epidemiology, and End Results registry were evaluated. Patients missing survival data or with multiple malignancies were excluded. Fine and Gray's sub-distribution hazards method was applied to evaluate the impact of age and stage on the competing risk of death in LG-EEC, HG-EEC or USC. Results: There were 121,028 eligible patients including 77.4% with LG-EEC, 14.8% with HG-EEC, and 7.8% with USC. The median age at diagnosis was 5 or 7 years older in women with HG-EEC or USC relative to LG-EEC, respectively. The proportion diagnosed with stage I vs stage IV disease varied by histology with 85.5% vs 2.3% with LG-EEC, 54.2% vs 17.0% with HG-EEC and 37.5% vs 30.1% with USC, respectively. CRD rates plateaued after 4 years whereas NCD rates continued to increase through 10 years from diagnosis across the histologic subtypes (Fig. 1A). The 5-year CRD rate increased incrementally by histology (5.7% with LG-EEC, 32.6% with HG-EEC or 51.2% with USC), older age (6.1% in Conclusions: Integration of age, stage and histology enhances the prediction of CRD and NCD risks for endometrial cancer patients. This comparison allows for enhanced personalization of cancer care and prioritized treatment of comorbid conditions, particularly when CRD risk is low. CRD risk increased dramatically over the first 4 years from diagnosis with higher stage than with older age and was incrementally higher in HG-EEC and USC relative to LG-EEC. Risk of NCD increased with age over 10-years from diagnosis but not by histology or stage.

Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study

BackgroundThe application of radiotherapy (RT) in pancreatic cancer remains controversial.AimThe aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer.MethodsFourteen thousand nine hundred seventy-seven patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test.ResultsPatients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14,977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001). Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P = 0.0039). Median survival time of 12,888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy (neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P<0.0001). Neoadjuvant RT (HR = 1.434, P = 0.023, 95% CI: 1.051–1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR = 0.904, P < 0.001, 95% CI: 0.861–0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher.ConclusionsThe study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma

PurposeThe 7th TNM classification summarizes renal cell carcinoma (RCC) with perirenal (PFI) and/or sinus fat invasion (SFI) as well as hilar vein involvement (RVI) as pT3a tumors. In this study, we aimed to determine the prognostic value of fat invasion (FI) in the different compartments and RVI for medium-term cancer-specific-survival (CSS) in pT3a RCC.Materials and methodsPatients with pT3a RCC were identified using an institutional database. All original pathological reports were reclassified according to the 7th TNM edition. The prognostic value of FI as well as divided into PFI, SFI, combined PFI + SFI, and RVI for CSS was assessed using univariate and multivariate Cox-regression analysis. Survival was estimated using the Kaplan–Meier method.ResultsMedian follow-up in 184 pT3a tumors was 38 months. FI was detectable in 153 patients (32.7% PFI, 45.1% SFI, 22.2% PFI + SFI), 31 patients showed RVI alone. Combined PFI + SFI increased the risk of cancer-related death compared to PFI (HR 3.11, p < 0.01), SFI (HR 1.84, p = 0.023) or sole RVI (HR 2.12, p = 0.025). In multivariate analysis, a combined PFI + SFI vs. PFI or SFI as the only compartment involved was confirmed as independent prognostic factor (HR 1.83, p = 0.029). Patients with FI and simultaneous RVI had significantly shorter CSS (HR 2.63, p < 0.01). In an unweighted model, the difference between patients with combined PFI + SFI and RVI and those with PFI alone was highest (HR 4.01, p = 0.029).ConclusionsThese results underline the subdivision of pT3a RCC depending on the location of FI and RVI for patient stratification.

Deep Learning Based HPV Status Prediction for Oropharyngeal Cancer Patients

Simple SummaryDetermination of human papillomavirus (HPV) status for oropharyngeal cancer patients depicts a essential diagnostic factor and is important for treatment decisions. Current histological methods are invasive, time consuming and costly. We tested the ability of deep learning models for HPV status testing based on routinely acquired diagnostic CT images. A network trained for sports video clip classification was modified and then fine tuned for HPV status prediction. In this way, very basic information about image structures is induced into the model before training is started, while still allowing for exploitation of full 3D information in the CT images. Usage of this approach helps the network to cope with a small number of training examples and makes it more robust. For comparison, two other models were trained, one not relying on a pre-training task and another one pre-trained on 2D Data. The pre-trained video model preformed best.Infection with the human papillomavirus (HPV) has been identified as a major risk factor for oropharyngeal cancer (OPC). HPV-related OPCs have been shown to be more radiosensitive and to have a reduced risk for cancer related death. Hence, the histological determination of HPV status of cancer patients depicts an essential diagnostic factor. We investigated the ability of deep learning models for imaging based HPV status detection. To overcome the problem of small medical datasets, we used a transfer learning approach. A 3D convolutional network pre-trained on sports video clips was fine-tuned, such that full 3D information in the CT images could be exploited. The video pre-trained model was able to differentiate HPV-positive from HPV-negative cases, with an area under the receiver operating characteristic curve (AUC) of for an external test set. In comparison to a 3D convolutional neural network (CNN) trained from scratch and a 2D architecture pre-trained on ImageNet, the video pre-trained model performed best. Deep learning models are capable of CT image-based HPV status determination. Video based pre-training has the ability to improve training for 3D medical data, but further studies are needed for verification.

New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer is one of the most frequent cancers in men and is a common cause of cancer-related death. Despite significant progress in the diagnosis and treatment of this tumor, patients who relapse after radical treatments inevitably develop metastatic disease. Patient stratification is therefore key in this type of cancer, and there is an urgent need for prognostic biomarkers that can define patients’ risk of cancer-related death. In the last 10 years, multiple prognostic factors have been identified and studied. Here, we review the literature available and discuss the most common aberrant genomic pathways in metastatic castration-resistant prostate cancer shown to have a prognostic relevance in this setting.

Association between Albumin, Total Bilirubin, and Uric Acid Serum Levels and the Risk of Cancer: A Prospective Study in a Korean Population.

PurposeIn this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population.Materials and MethodsA total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed.ResultsUA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01–1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88–0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80–0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83–0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer.ConclusionThe findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.

Usefulness of pre-thyroidectomy neutrophil–lymphocyte, platelet–lymphocyte, and monocyte–lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

OBJECTIVE:This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC).METHODS:This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively.RESULTS:PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity).CONCLUSION:Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.