Search

Purpose: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). Methods: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine–Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. Results: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05–1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13–2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23–1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11–2.12; P = 0.009). Conclusion: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the cause‐effect relationship between renal tubular damage and non‐cancer mortality in the general Japanese population. We conducted a 19‐year cohort study including 1110 men and 1,03 women who lived in three cadmium‐non‐polluted areas in 1993 or 1994. Mortality risk ratios based on urinary β2‐microglobulin (β2MG) and N‐acetyl‐β‐glucosaminidase (NAG) concentrations were estimated for specific non‐cancer diseases using the Fine and Gray competing risks regression model. In men, continuous urinary NAG (+1 μg/g cre) concentrations were significantly correlated with increased mortality caused by diseases of the respiratory system (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03–1.15). Urinary β2MG (+100 μg/g cre) concentrations were significantly correlated with increased mortalities caused by kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00–1.03), renal diseases (HR: 1.01, 95% CI: 1.00–1.03), renal failure (HR: 1.02, 95% CI: 1.00–1.03), and external causes of mortality (HR: 1.01, 95% CI: 1.00–1.02). In women, urinary NAG (+1 μg/g cre) concentrations were significantly associated with increased mortality caused by ischemic heart diseases (HR: 1.02, 95% CI: 1.00–1.04) and kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00–1.04). Urinary β2MG (+100 μg/g cre) concentrations were significantly correlated with increased mortality caused by cardiovascular diseases (HR: 1.01, 95%CI: 1.00–1.02), ischemic heart diseases (HR: 1.01, 95%CI: 1.00–1.02), and kidney and urinary tract diseases (HR: 1.02, 95% CI: 1.01–1.03). The present study indicates that renal tubular damage was significantly related to several non‐cancer disease causes of mortality in Japan's general population living in cadmium‐non‐polluted areas. We evaluated the effect of renal tubular damage on non‐cancer mortality, by conducting a 19‐year cohort study in three cadmium‐non‐polluted areas in Japan. Mortality risk estimates based on urinary NAG and β2MG concentrations were significantly higher for respiratory, renal, and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The changes in body composition are early adverse effects of androgen deprivation therapy (ADT); however, their prognostic impact remains unclear in prostate cancer. This study aimed to evaluate the association between body composition changes and survival in patients with high-risk prostate cancer. We measured the skeletal muscle index (SMI) and total adipose tissue index (TATI) at the L3 vertebral level using computed tomography at baseline and within one year after initiating ADT in 125 patients with high-risk prostate cancer treated with radiotherapy and ADT between 2008 and 2018. Non-cancer mortality predictors were identified using Cox regression models. The median follow-up was 49 months. Patients experienced an average SMI loss of 5.5% over 180 days (95% confidence interval: -7.0 to -4.0; p <0.001) and TATI gain of 12.6% over 180 days (95% confidence interval: 9.0 to 16.2; p <0.001). Body mass index changes were highly and weakly correlated with changes in TATI and SMI, respectively (Spearman ρ for TATI, 0.78, p <0.001; ρ for SMI, 0.27, p =0.003). As a continuous variable, each 1% decrease in SMI was independently associated with a 9% increase in the risk of non-cancer mortality (hazard ratio: 1.09; p =0.007). Moreover, the risk of non-cancer mortality increased 5.6-fold in patients with SMI loss ≥5% compared to those with unchanged SMI (hazard ratio: 5.60; p =0.03). Body mass index and TATI were not associated with non-cancer mortality. Muscle loss during ADT is occult, independent of weight change, and independently associated with increased non-cancer mortality in patients with high-risk prostate cancer. [ABSTRACT FROM AUTHOR]

The changes in body composition are early adverse effects of androgen deprivation therapy (ADT); however, their prognostic impact remains unclear in prostate cancer. This study aimed to evaluate the association between body composition changes and survival in patients with high-risk prostate cancer. We measured the skeletal muscle index (SMI) and total adipose tissue index (TATI) at the L3 vertebral level using computed tomography at baseline and within one year after initiating ADT in 125 patients with high-risk prostate cancer treated with radiotherapy and ADT between 2008 and 2018. Non-cancer mortality predictors were identified using Cox regression models. The median follow-up was 49 months. Patients experienced an average SMI loss of 5.5% over 180 days (95% confidence interval: -7.0 to -4.0; p

Objective: To investigate association of preoperative C‐reactive protein (CRP) and non‐cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). Patients and Methods: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1–2 RCC from 2006 to 2017, excluding all cases of cancer‐specific mortality. Descriptive analyses were obtained between the pre‐treatment normal‐CRP (≤5 mg/L) and elevated‐CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3–4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan–Meier analysis was used to obtain survival estimates for outcomes. Results: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal‐CRP group, n = 963; elevated‐CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African‐Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2, P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan–Meier analysis revealed significantly higher 5‐year NCM in the elevated‐CRP group vs the normal‐CRP group (98% vs 80%, P < 0.001). Conclusions: Pre‐treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1–2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron‐sparing strategies, which may be prioritised if oncologically appropriate. [ABSTRACT FROM AUTHOR]

Background Understanding the burden of competing (non-breast cancer) mortality is important for the growing number of breast cancer survivors. We quantity these patterns, and the impact of two leading non-cancer causes of death, within ten years of breast cancer diagnosis. Methods Population based cancer registry study of 23,809 women aged 50–79 diagnosed with first primary breast cancer in Queensland, Australia, 1997 to 2012 with additional data linkage to identify individual non-cancer mortality causes. Flexible parametric competing-risks models were used to estimate the crude and adjusted probabilities of death. Results While overall mortality increased with age at diagnosis, this effect was strongest for non-cancer (such as cardiovascular and cerebrovascular disease) mortality. Women diagnosed with advanced breast cancer had a higher crude probability of breast cancer death (23.1% versus 4.5% for localised) but similar probability of competing mortality (11.6% versus 11.3%). Within each category of spread of disease, the probability of breast-cancer deaths remained relatively constant with age, while the probability of competing deaths increased. The 10-year probability of dying from breast cancer was 3.7%, 4.2% and 5.6% among women with localised disease aged 50 to 59, 60–69 and 70–79 respectively, but 3.1%, 7.8% and 22.9% for competing mortality. Increasing age, advanced disease and being unpartnered were independently associated with increased risk of breast cancer and competing deaths. Conclusions Promotion of improved health behaviors after a cancer diagnosis and development of individualized strategies for clinical management should be prioritized as part of optimal care for breast cancer survivors. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the association between HbA1c variability and mortality due to all causes, cancer, and non-cancer in patients with type 2 diabetes independently of mean HbA1c levels. Methods: We enrolled 754 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, had been followed for at least 2 years, and had undergone four or more HbA1c determinations. Patients were followed through June 2012. The standard deviation (SD) or coefficient of variation (CV) was used as a measure of HbA1c variability. Risk of death was evaluated by multivariate Cox proportional hazard models. Results: Through June 2012, 63 patients died. Hazard ratios (HRs) for all-cause mortality and non-cancer mortality including cardiovascular diseases (CVD) increased across tertiles of both HbA1cSD and HbA1cCV. HRs for cancer mortality did not increase across tertiles of either HbA1cSD or HbA1cCV. Using a stepwise regression method, both HbA1cSD and HbA1cCV predicted all-cause mortality, especially non-cancer mortality. In contrast, mean HbA1c predicted cancer mortality. Conclusions: HbA1c variability is a predictor of all-cause mortality, especially non-cancer mortality including CVD, in patients with type 2 diabetes, independent of mean HbA1c level. In contrast, mean HbA1c, but not HbA1c variability, might predict cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Evaluating the cost-effectiveness of breast cancer screening requires estimates of the absolute risk of breast cancer, which is modified by various risk factors. Breast cancer incidence, and thus mortality, is altered by the occurrence of competing events. More accurate estimates of competing risks should improve the estimation of absolute risk of breast cancer and benefit from breast cancer screening, leading to more effective preventive,diagnostic, and treatment policies. We have previously described the effect of breast cancer risk factors on breast cancer incidence in the presence of competing risks. In this study, we investigate the association of the same risk factors with mortality as a competing event with breast cancer incidence.Methods: We use data from the Canadian National Breast Screening Study, consisting of two randomized controlled trials, which included data on 39 risk factors for breast cancer. The participants were followed up for the incidence of breast cancer and mortality due to breast cancer and other causes. We stratified all-cause mortality into death from other types of cancer and death from non-cancer causes. We conducted separate analyses for cause-specific mortalities.Results: We found that "age at entry" is a significant factor for all-cause mortality, and cancer-specific and non-cancer mortality. "Menstruation length" and "number of live births" are significant factors for all-cause mortality, and cancer-specific mortality. "Ever noted lumps in right/left breasts" is a factor associated with all-cause mortality, and non-cancer mortality.Conclusions: For proper estimation of absolute risk of the main event of interest common risk factors associated with competing events should be identified and considered. [ABSTRACT FROM AUTHOR]

To investigate the pattern of non-cancer deaths and to determine whether there is excess mortality from non-cancer causes among Korean long-term survivors of adult cancer. We merged national cancer registry data and national death registration data to determine non-cancer death patterns of 243,713 people who were diagnosed with cancer from 1993 to 2000 and who survived ≥5 years. We calculated standardized mortality ratios (SMRs) by an indirect standardization method. Of the patient population, 26,498 (10.9%) had died as of December 2005; the cause of death for 6,364 (24.0%) of those was not cancer. The proportion of non-cancer mortality increased with age at diagnosis and correlated with the 5-year survival rate ( r = 0.336 for women, 0.571 for men). Although the risk for non-cancer death was lower among long-term survivors in general (SMR, 0.78; 95% CI, 0.76–0.80), it was higher among younger survivors (SMR, 1.23–2.50, for those who died before 50) than the general population. Survivors had an elevated suicide rate (SMR, 1.28; 95% CI, 1.15–1.42), especially male (SMR, 1.35; 95% CI, 1.19–1.53) and stomach cancer survivors (SMR, 1.38; 95% CI, 1.14–1.66). Appropriate medical attention for long-term adult cancer survivors, especially younger survivors, is warranted to prevent premature deaths from non-cancer causes. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the extent to which the survival outcomes of patients with N2-III non-small cell lung cancer (NSCLC) following surgery differ by histological subtype., Methods: Patients with N2-III NSCLC receiving surgery between 2010 to 2016 were included using the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models were used to identify risk factors associated with overall survival (OS) and non-cancer mortality. The Kaplan-Meier method with log-rank tests was used to estimate survival. Propensity score matching (PSM) was used. Statistical significance was defined as P<0.05. Statistical analyses were done with IBM SPSS 23.0., Results: Ultimately, 2,501 patients with stage N2-III NSCLC receiving surgery were included: 1,891 (75.6%) patients had adenocarcinoma (AC), and 610 (24.4%) patients had squamous cell cancer (SCC). The percentages of patients with AC and SCC receiving chemotherapy and postoperative radiotherapy (PORT) were comparable. In multivariate analysis, histology remained a significant predictor for OS and non-cancer mortality after adjusting for other clinical factors (P<0.05). Based on clinical factors, 522 patients with SCC were ultimately matched with 518 patients with AC using PSM. The 5-year OS of SCC patients after matching was much worse than that of AC patients (36.3% vs. 41.5%; P=0.018), and the 5-year non-cancer mortality of SCC patients was much higher than that of AC patients (18.8% vs. 4.8%; P=0.001)., Conclusions: Among patients with stage N2-III NSCLC following surgery, those with SCC had worse OS than those with AC, due to the higher percentage of patients dying from non-cancer causes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4357). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)