Non-cancer Deaths Research Articles

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function.

Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease. To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria. Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence. After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.

Quantifying the Interplay Between Smoking and Human Papillomavirus in Risk Stratification of Patients with Oropharyngeal Cancer Undergoing Radiotherapy

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. (Gillison M, et al. J Natl Cancer Inst. 2008) Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral mediated (HPV-) OPSCC, the improvement is not uniform. (Vadwa N, et al. Int J Radiat Oncol Biol Phys. 2019) We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. We sought to integrate smoking into current staging system after statistically identifying a threshold value for smoking pack-years (PY) that is associated with worse survival. We also aimed at modeling the differential competing risks of treatment failure and death in HPV+ heavy and non-heavy smokers. We performed a retrospective review of patients with OPSCC treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to statistically define tobacco exposure associated with survival (p<0.05). We identified 611 OPSCC patients with concordant p16 and HPV testing results. Eighty-nine percent of patients were HPV+; 50% of whom were non-smokers compared to only 20% of HPV- patients. Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 PY as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. A competing risk analysis of modes of failure and causes of death showed a higher risk of loco-regional failure and non-cancer deaths among HPV+ >30 PY patients compared to HPV+ ≤30 PY patients. Tobacco exposure beyond 30 PY can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.

Characteristics Associated With Nonreceipt of Surveillance Testing and the Relationship With Survival in Stage II and III Colon Cancer.

We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years' follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio=1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio=1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.

409P Causes of mortality in elderly UICC stage III colon cancer (CC) patients (pts.) - Tumor related death and competing risks from the Colopredict Plus (CPP) registry

CC is a disease of the elderly patients (pts.) with a median age of 73 years (yrs.) in Germany. Since elderly pts. are underrepresented in randomized clinical trials, data on adjuvant chemotherapy (ACT) are scarce. We aimed to characterize the use of ACT and cancer related and non-cancer related death in an elderly cohort of the German CPP registry.

Cancer Bereavement and Depression Symptoms in Older Spouses: The Possible Modifying Role of the Circadian Rest-Activity Rhythm

ABSTRACT Objectives This study examines the associations of cancer death and aspects of the 24-h circadian rest-activity rhythm (RAR) on depression symptoms in older spouses. Methods Participants included 46 adults aged 60–94 years (M = 73 years) who experienced the death of a spouse. We tested a multivariate model using cancer death (vs. non-cancer death) and RAR variables as correlates of depression symptoms while controlling for age, sex, physical illness burden, and preparedness for death. We also present a case example to describe the behavioral activity patterns of a participant bereaved by cancer. Results Cancer death was associated with elevated levels of depression symptoms. However, the timing of the RAR moderated this association. Cancer bereavement was associated with depression symptoms when participants “settled-down” after 11:00 PM. The case example illustrates how intrusive thoughts about death quality impacts a widower’s drive to stay busy with daily activities. Conclusions Settling down earlier in the evening is important for older spouses bereaved by cancer, in terms of fewer symptoms of depression. Clinical implications Objectively specifying the activity patterns of older spouses bereaved by cancer is a promising avenue for interventions that aim to reduce depression symptoms.

Evaluation of Racial Disparities in Hospice Use and End-of-Life Treatment Intensity in the REGARDS Cohort

Although hospice use is increasing and patients in the US are increasingly dying at home, racial disparities in treatment intensity at the end of life, including hospice use, remain. To examine differences between Black and White patients in end-of-life care in a population sample with well-characterized causes of death. This study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, an ongoing population-based cohort study with enrollment between January 25, 2003, and October 3, 2007, with linkage to Medicare claims data. Multivariable logistic regression models were used to examine racial and regional differences in end-of-life outcomes and in stroke mortality among 1212 participants with fee-for-service Medicare who died between January 1, 2013, and December 31, 2015, owing to natural causes and excluding sudden death, with oversampling of Black individuals and residents of Southeastern states in the United States. Initial analyses were conducted in March 2019, and final primary analyses were conducted in February 2020. The primary outcomes of interest were hospice use of 3 or more days in the last 6 months of life derived from Medicare claims files. Other outcomes included multiple hospitalizations, emergency department visits, and use of intensive procedures in the last 6 months of life. Cause of death was adjudicated by an expert panel of clinicians using death certificates, proxy interviews, autopsy reports, and medical records. The sample consisted of 1212 participants (630 men [52.0%]; 378 Black individuals [31.2%]; mean [SD] age at death, 81.0 [8.6] years) of 2542 total deaths. Black decedents were less likely than White decedents to use hospice for 3 or more days (132 of 378 [34.9%] vs 385 of 834 [46.2%]; P < .001). After stratification by cause of death, substantial racial differences in treatment intensity and service use were found among persons who died of cardiovascular disease but not among patients who died of cancer. In analyses adjusted for cause of death (dementia, cancer, cardiovascular disease, and other) and clinical and demographic variables, Black decedents were significantly less likely to use 3 or more days of hospice (odds ratio [OR], 0.72; 95% CI, 0.54-0.96) and were more likely to have multiple emergency department visits (OR, 1.35; 95% CI, 1.01-1.80) and hospitalizations (OR, 1.39; 95% CI, 1.02-1.89) and undergo intensive treatment (OR, 1.94; 95% CI, 1.40-2.70) in the last 6 months of life compared with White decedents. Despite the increase in the use of hospice care in recent decades, racial disparities in the use of hospice remain, especially for noncancer deaths. More research is required to better understand racial disparities in access to and quality of end-of-life care.

The clinicopathological characteristics and genetic alterations between younger and older gastric cancer patients with curative surgery.

Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed using mass spectrometric single nucleotide polymorphism genotyping technology, including 68 validated mutations within eight genes (TP53, ARID1A, BRAF, and the PI3K/AKT pathway) previously reported in relation to age. Younger patients were more likely to be female and have poor cell differentiation, diffuse-type tumors, less lymphovascular invasion, fewer liver metastases, and better 5-year overall survival (OS) (68.0% vs. 54.6%, P<0.001) and disease-free survival (DFS) (65.4% vs. 53.0%, P<0.001) rates than older patients. Regarding the genetic alterations, older patients had more microsatellite instability-high (MSI-H) tumors and more ARID1A mutations than younger patients. Younger patients had significantly better OS and DFS rates than older patients for each pathological Tumor, Node, Metastasis (TNM) stage. Older patients had a significantly higher non-cancer related death rate than younger patients (36.2% vs. 12.3%, P<0.001). Age was an independent prognostic factor in GC. In conclusion, age was associated with different clinicopathological features and genetic alterations in GC with curative surgery.

Abstract LB-164: Characteristics associated with nonreceipt of post-treatment surveillance testing in stage II and III colon cancer survivors and the subsequent relationship with overall survival and the cumulative incidence of cancer death

Abstract Background: Recent studies have reported no survival benefit associated with more intensive post-treatment surveillance testing in colon cancer survivors compared to less testing. However, few studies have evaluated characteristics of patients who fail to receive any surveillance testing and the relationship with survival and cancer-specific outcomes. The purpose of this study was to assess the association between sociodemographic and clinical characteristics of stage II and III colon cancer patients with nonreceipt of surveillance testing and the subsequent outcomes of overall survival and the cumulative incidence of cancer death. Methods: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Stage II and III colon cancer patients diagnosed between 2002 to 2009 and between 66 to 84 years of age were eligible. A minimum of three years post-treatment follow-up was required for inclusion. Receipt of recommended surveillance testing–including carcinoembryonic antigen, computed tomography, and colonoscopy–was assessed for each year of the required three year follow-up. Patients were categorized as having received any surveillance testing (Any Testing) vs. none (No Testing). Modified Poisson regression was used to obtain risk ratios for the relative likelihood of not receiving any surveillance testing. Cox regression was used to obtain estimates of 5- and 10-year overall survival. Modified Cox regression was used to obtain 5- and 10-year estimates of the cumulative incidence of cancer-specific mortality. In addition, subdistribution hazard ratios (SHRs) with 95% confidence intervals (CIs) were obtained for the cumulative incidence of cancer-specific and noncancer death. Results: There were 16,009 stage II and III colon cancer cases available for analysis, of whom 8.6% (n = 1,382) received No Testing. Compared to patients who received Any Testing, colon cancer survivors who received No Testing were more likely to be older, black race, separated/divorced, diagnosed later (2007-2009), have state buy-in coverage, urban, reside in the West/Pacific regions, have stage III disease, not have received chemotherapy, and to have zero or ≥ 4 comorbid conditions. Within disease stage, patients who received No Testing were more likely to experience death to any cause and cancer death than survivors who received surveillance testing. Accounting for competing causes of death, No Testing patients also experienced an increased rate of 10-year cancer death that was greater for stage III patients (SHR = 1.84, 95% CI, 1.48-2.29) than stage II patients (SHR = 1.44, 95% CI, 1.15.-1.78). Conclusions: This study identified characteristics of colon cancer survivors that were associated with failure to receive post-treatment surveillance testing. The No Testing group also experienced an increased risk of overall and cancer-specific death that was higher for stage III patients. Future studies are warranted to confirm these findings. Citation Format: Robert B. Hines, Md Jibanul Haque Jiban, Eunkyung Lee, Cassie Odahowski, Audrey Wallace, Spencer J. E. Adams, Saleh Rahman, Shunpu Zhang. Characteristics associated with nonreceipt of post-treatment surveillance testing in stage II and III colon cancer survivors and the subsequent relationship with overall survival and the cumulative incidence of cancer death [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-164.

Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults: Singapore Chinese Health Study.

Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of the Asian population. Relative telomere lengths in genomic DNA from peripheral blood samples were quantified using a validated quantitative real-time PCR among 26 540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer and deaths by quintiles of telomere length were calculated using the Cox proportional hazards regression method with adjustment for age, sex and other potential confounders. After baseline blood collection, 4353 persons developed cancer and 7609 died. Participants with the longest decile of telomeres had a 26% (95% CI: 11%-44%) higher risk of total cancer incidence compared to the shortest decile after controlling for age, sex and other potential founders (Ptrend < .0001). In contrast, longer telomeres were associated with lower risk of all-cause mortality (HR = 0.93; 95% CI: 0.84-1.03), noncancer death (HR = 0.81; 95% CI: 0.71-0.92), specifically, death from chronic obstructive pulmonary disease and pneumonia (HR = 0.79, 95% CI: 0.70-0.89) and digestive diseases (HR = 0.60, 95% CI: 0.42-0.88). Our findings demonstrated that longer telomeres are associated with increased risk of cancer development overall and several common cancer types including breast, rectal, prostate, pancreatic cancer and lung adenocarcinoma. Our study also confirmed that longer telomeres are associated with a reduced risk of noncancer related death.

1098 - Risk adapted comparison between cancer recurrence and non-cancer related death in patients treated with robot-assisted radical cystectomy for muscle invasive bladder cancer

1098 - Risk adapted comparison between cancer recurrence and non-cancer related death in patients treated with robot-assisted radical cystectomy for muscle invasive bladder cancer

Abstract PR05: Fine particulate matter and mortality among pediatric, adolescent, and young adults with cancer

Abstract Background: Fine particulate matter air pollution (PM2.5) is associated with mortality in the adult population and in adults diagnosed with lung and breast cancer. The effect of PM2.5 on mortality in pediatric, adolescent, and young adults (AYA) diagnosed with cancer is unknown. We examine the association between PM2.5 and mortality among pediatric and AYAs diagnosed with cancer in Utah, a state with severe PM2.5 pollution. Methods: We identified 2,631 pediatric cancer patients aged 0 to 14 years and 14,575 AYA cancer patients aged 15 to 39 years diagnosed from 1986 to 2016. Patients were followed from first diagnosis date to five or ten years post-diagnosis, death, or emigration out of Utah as indicated by Utah Population Database records. We estimated average PM2.5 at each subject’s ZIP code at diagnosis from the first diagnosis date to the five- and ten-year follow-up dates, death, or emigration. We estimated the effect of five- and ten-year PM2.5 exposure on mortality at five and ten years post-diagnosis. Cox models controlled for parental education, sex, diagnosis year, and cancer stage/severity. Pediatric and AYA cancers were run in separate models. Pediatric cancers were stratified by International Classification of Childhood Cancer categories and AYA cancers were stratified by the WHO Classification for AYA cancers. Models were run for all-cause mortality and cancer-mortality, with noncancer deaths included as competing risks. Results: We found 571 (20%) deaths among pediatric patients and 3,064 (19.6%) deaths among AYA patients. Most deaths occurred within five years of diagnosis for both groups (83% and 67%, respectively). Cancer was the predominant cause of death among pediatric (94%) and AYA patients (92%). Pediatric patients were exposed to mean PM2.5 of 9.13 μg/m3 and AYA patients were exposed to a mean PM2.5 of 8.31 μg/m3. During five years of follow-up, we found significant associations between PM2.5 and all-cause and cancer mortality for pediatric central nervous system (CNS) patients (all-cause: 1.07 [95%CI: 1.01-1.13], cancer: 1.10 [1.04-1.17]). Among AYAs, we found that five-year PM2.5 exposure was associated with all-cause mortality and cancer-mortality among CNS (all-cause: 1.07 [1.03-1.12], cancer: 1.09 [1.04-1.14]) and carcinoma patients (all-cause: 1.03 [1.01-1.06], cancer: 1.04 [1.02-1.07]). During ten years of follow-up, PM2.5 had a significant association with all-cause and cancer-mortality among pediatric leukemia (all-cause: 1.09 [1.03-1.15], cancer: 1.09 [1.03-1.16]) and CNS patients (all-cause: 1.10 [1.05-1.15], cancer: 1.12 [1.06-1.17]). Among AYAs, ten-year PM2.5 was associated with all-cause and cancer-mortality among CNS (all-cause: 1.05 [1.02-1.09], cancer: 1.06 [1.03-1.10]), melanoma (all-cause: 1.07 [1.02-1.12], cancer: 1.08 [1.02-1.14]), and carcinoma patients (all-cause: 1.06 [1.04-1.08], cancer: 1.07 [1.05-1.09]). Conclusion: PM2.5 is associated with mortality among pediatric and AYA cancer patients. This abstract is also being presented as Poster A35. Citation Format: Judy Y. Ou, Heidi A. Hanson, Joemy M. Ramsay, Heydon Kaddas, C. Arden Pope, Claire L. Leiser, James A. VanDerslice, Anne C. Kirchhoff. Fine particulate matter and mortality among pediatric, adolescent, and young adults with cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR05.

Cardiovascular risk and undertreatment of dyslipidemia in lung cancer survivors: A nationwide population-based study

BackgroundIn lung cancer survivors, cardiovascular diseases (CVDs) are the leading cause of noncancer deaths. Nonetheless, there is lack of information on management of dyslipidemia, a major risk factor for future CVD events, in lung cancer survivors. This study aimed to assess dyslipidemia management and prevalence of statin eligibility in lung cancer survivors. MethodsFrom the Korean National Health Insurance Service database, we selected 7349 lung cancer survivors who received surgery for lung cancer from 2007 to 2014. We used descriptive statistics for analyses of dyslipidemia management status on the basis of the National Cholesterol Education Program Adult Treatment Panel III guidelines. We also identified those who met the criteria for treatment on the basis of CVD risk according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) guidelines. ResultsThe overall awareness and treatment rates for lung cancer survivors with dyslipidemia were 31.8% and 29.7%, respectively. The overall control rate for those receiving treatment was 88.7%, but was lowest in the highest risk group (78.1%). Furthermore, undertreatment of dyslipidemia was more prominent in young, male lung cancer survivors and those diagnosed with lung cancer within 3 years. Among those not receiving treatment for dyslipidemia, 61.7% were indicated for statin according to the ACC/AHA guidelines. ConclusionOver half of lung cancer survivors were not receiving treatment, although they were eligible for statin under current guidelines. To reduce noncancer mortality, statin use and adequate management of CVD risk factors should be encouraged in lung cancer survivors.

Cancer in chronic heart failure patients in the GISSI-HF trial.

Cancer complicating heart failure (HF) is an emerging issue. We investigated it in the GISSI-HF trial, which uniquely included patients with malignancies if deemed likely to allow follow-up. At enrolment, 256 of 6913 participants in GISSI-HF (3.7%) had a tumour diagnosis, which was malignant (cancer) in 145 (2.1%). Patients with cancer were older and more often former smokers, had lower body mass index, lower left ventricular ejection fraction (LVEF), less implanted devices, lower glucose and haemoglobin and higher uric acid levels than those without cancer. During a median 4-year follow-up, cardiovascular (CV), non-CV non-cancer and cancer death occurred in 1477, 272 and 220 subjects (75%, 13.8% and 11.2% of total mortality, respectively). Cancer at trial entry portended an increased risk of all-cause mortality after accounting for age and confounders (HR 1.33, 95%CI 1.02-1.73), which was attributable to cancer-specific mortality. Among the 6657 patients without any tumour at enrolment, 1879 subsequently died. CV, non-CV non-cancer and cancer causes accounted for 1422 (75.7%), 261 (13.9%) and 196 (10.4%) of these deaths, respectively, median time to specific death being 22, 25 and 30months (P<.0001). Patients facing cancer vs CV death had lower NYHA class, slower heart rate, higher blood pressure, higher LVEF, shorter HF history, less diuretic use, lower creatinine and uric acid and higher haemoglobin and cholesterol. Even when considered not aggressive, concomitant cancer worsens HF prognosis. The inverse relationship between HF severity and cancer death in the absence of prior tumour warrants further study.

Risk of cancer-specific death for patients diagnosed with neuroendocrine tumors: A population-based analysis.

4605 Background: While patients with neuroendocrine tumours (NETs) are known to experience prolonged overall survival, the contribution of cancer-specific and non-cancer deaths is undefined. We examined cancer-specific and non-cancer death after NET diagnosis. Methods: We conducted a population-based retrospective cohort study of adult patients with NETs from 2001-2015 by linking administrative healthcare datasets. Using competing-risks methods, we estimated the cumulative incidence of cancer-specific and non-cancer death and stratified by primary NET site and metastatic status. Sub-distribution hazard models examined prognostic factors. Results: Among 8,607 included patients, median follow-up was 42 months (interquartile range: 17-82). The risk of cancer-specific was higher than that of non-cancer death, with 27.3% (95%CI: 26.3-28.4%) and 5.6% (95%CI: 5.1-6.1%) at 5 years. Cancer-specific deaths largely exceeded non-cancer deaths in synchronous and metachronous metastatic NETs. Patterns varied by primary tumour site, with highest risks of cancer-specific death in broncho-pulmonary and pancreatic NETs. For non-metastatic gastric, small intestine, colonic, and rectal NETs, the risk of non-cancer death exceeded that of cancer-specific deaths. Advancing age, higher material deprivation, and metastases were independently associated with higher hazards, and female sex and high comorbidity burden with lower hazards of cancer-specific death. Conclusions: Among all NETs, the risk of dying from cancer is higher than that of dying from other causes. Heterogeneity exists by primary NET site. Some patients with non-metastatic NETs are more likely to die from non-cancer than from cancer causes. This information is important for counselling, decision-making, and design of future trials. Cancer-specific mortality should be included in outcomes when assessing treatment strategies.

Cancer-Attributable Medical Costs for Colorectal Cancer Patients by Phases of Care: What Is the Effect of a Prior Cancer History?

Medical care costing studies have excluded patients with a prior cancer history. This study aims to update methods for estimating medical care costs attributable to cancer and to evaluate the effect of a prior history of cancer on costs for colorectal cancer (CRC) patients. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and matched cancer patients to controls without cancer to estimate cancer-attributable costs by phases of care using Medicare 2007-2013 claims. CRC annualized average cancer-attributable costs were $56.0 K, $5.3 K, $92.5 K, and $24.3 K in the initial, continuing, and end-of-life cancer and noncancer death phases, respectively, in 2014 dollars. Costs were higher for patients diagnosed with more advanced stage, younger ages, and nonwhite races. Costs for patients with prior cancers were consistently higher than patients without prior cancers, especially in the continuing (4.9 K vs 7.2 K) and end-of-life noncancer death (22.7 K vs 30.0 K). Our CRC costs improve previous estimates by using more recent data and updated methods.

Improved long-term results of intensity-modulated radiotherapy for a non-endemic European nasopharyngeal carcinoma cohort: single-center retrospective study.

Report our matured outcomes of European nasopharyngeal carcinoma (NPC) treatment from a non-endemic region in the IMRT era. We reviewed 109 consecutive patients with biopsy proven NPC treated between 2009 and 2013. All received IMRT as per RTOG 0615. Toxicity was scored accordingly to CTCAE 4.03. Platinum-based chemotherapy was delivered following the Intergroup 0099. Median age of 53 years; 97% Caucasian; 74% male; 72% WHO grade III; 43% T1; 14% T2; 18% T3, 25% T4; 17% N0; 17% N1; 39% N2; 27% N3. Compliance to adjuvant chemotherapy was 88%. With a median follow up of 56 months, the 4-year local control was 90.2% (88.6% for T1; 100% for T2; 85% for T3; and 91.7% for T4), the 4-year distant metastases-free survival was 86% and an overall survival rate was 77%. Local control and survival were better in G3 (p < 0.001 and p = 0.032, respectively). Xerostomia was the most frequent late toxicity in 55% (n = 60). Hypothyroidism requiring hormonal reposition occurred in 15.5% (n = 17). From the 36 deaths, 20 were due to distant metastases, 3 grade 5 toxicity, 2 from local progression, 5 non-cancer deaths and unknown cause in the remaining 6. On multivariable analysis, age (p = 0.017), local recurrence and distant metastases were associated with death (p < 0.001, both). Our matured data from the IMRT era showed a major improvement from our 3D cohort series reaching excellent local and regional control, even in T4. Local recurrences, despite few, and distant metastases were correlated with the risk of death.

Cardiovascular Disease among Breast Cancer Survivors.

Background:Among breast cancer survivors age > 50 years, deaths due to cardiovascular disease account for 35% of non-cancer related deaths. The increases in cardiovascular disease among breast cancer survivors is due to the cardiotoxic effects of breast cancer treatment and to overlapping risk factors for breast cancer and cardiovascular disease.Methods:We conducted a study of a sample of 164 breast cancer patients in order to examine the frequency of cardiovascular disease. The overall objective was to examine the frequency of high blood pressure, myocardial infarction, cardiomyopathy, congestive heart failure, stroke, and venous thrombosis/thromboembolism among women who have been diagnosed with stage I-IV breast cancer and who had completed primary therapy for the disease. Data were collected by postal survey and abstraction of electronic medical records.Results:A high percentage of the women (62.8%) had a reported history of high blood pressure. Fifty percent of the women had a reported history of high cholesterol. About 8.3% of the women were current smokers and 36.0% were former smokers. About 23.8% of the women had a reported history of diabetes. About 4.9% of the women had a reported history of congestive heart failure and 6.1% had a history of stroke.Discussion:Additional studies are needed of cardiovascular risk factors and adverse cardiovascular events among breast cancer survivors. Of particular concern is whether patients with hypertension, hypercholesterolemia, and diabetes are receiving appropriate therapy to reduce their cardiovascular risk and prevent morbidity and mortality from adverse cardiovascular events.

Partial vs. radical nephrectomy and the risk of all-cause mortality, cardiovascular, and nephrological outcomes.

The study's objective was to examine the effects of renal-preservation surgery on long-term mortality, cardiovascular outcomes, and renal-related outcomes. We performed a retrospective cohort study of all partial (n=575) and radical nephrectomies (n=882) for tumors ≤7 cm in diameter between 2002 and 2010 across three academic centers in Ontario, Canada. We linked records from provincial databases to assess patient characteristics and outcomes (median seven years' followup using retrospective data). A weighted propensity score was used to reduce confounding. The primary outcome was all-cause mortality. Secondary outcomes included hospitalization with major cardiovascular events, non-cancer related mortality, kidney cancer-related mortality, and dialysis. Mean one-year postoperative estimated glomerular filtration rate (eGFR) was 71 mL/min/1.73 m2 in the partial group and 52 mL/min/1.73 m2 in the radical group. Partial nephrectomy was associated with a lower risk of all-cause mortality in the first five years after surgery (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.27-0.66), which did not extend beyond five years (HR 1.01, 95% CI 0.68-1.49). Kidney cancer-related mortality was lower in the partial compared to the radical group for the first four years after surgery (HR 0.16, 95% CI 0.04-0.72). There were no significant differences between the groups for cardiovascular outcomes or non-cancer related deaths. Overall survival and cancer-specific survival was reduced in radical nephrectomy patients. However, despite reduced renal function in the radical nephrectomy group, non-cancer-related death, cardiovascular events, and dialysis were not significantly different between groups. Long-term benefits of partial nephrectomy may be less than previously believed.

Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists.

34 Background: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists. Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR &gt; 1 reflects a disproportionality signal that more AEs are observed than expected. Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any subgrouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists. Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.

Causes of death following neuroendocrine tumors diagnosis: A United States population-based analysis.

630 Background: Neuroendocrine tumors (NET) are heterogeneous in terms of prognosis based on location, grade, and stage. In this study we report causes of deaths (COD) in patients with NET. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to query data of NET patients diagnosed between 2000 and 2016 and report COD following NET diagnosis. Results: We reviewed 94,399 NET cases of which 38,692 died during the follow-up period. The highest number of deaths (5,721) occurred within less than a year following grade 3 (G3) NET diagnosis while most deaths in grade 1/2 (G1/G2) cases occurred within 1-5 years of diagnosis (1,889 and 987, respectively). During the first year of diagnosis, most deaths were from NETs (73%), followed by other cancers (11.2%) and cardiac diseases (CD) (4.6%). As time passed, NET deaths decreased to be responsible for 24.3% of deaths after &gt; 10 years of diagnosis, while other cancers (14%) and CD (19.7%) became more common. When dividing NET cases by grade, NETs were responsible for 42.8%, 63.4%, and 81.2% of deaths in G1, G2, and G3, respectively, while other cancers were responsible for 16.2%, 11.8%, and 7.2% of deaths, respectively and CDs were responsible for 12.3%, 7.2%, and 3.2% of deaths, respectively. For G1 localized NET: non-NET cancers (22.2%) was the most common COD followed by NET (19.7 %) and CD (16.8%). For G2 localized NET, NET was COD in 31.1% of cases followed by non-NET cancers (22.4%) and CD (13.8%). In metastatic disease, NET was the most common COD regardless of grade. Conclusions: In G1 and G2 localized NET, deaths were mostly secondary to non-NET causes. Therefore, counseling patients regarding survivorship with cancer-screening and focusing on prevention from non-cancer deaths is important. On the other hand, NET is responsible for most deaths in metastatic NET regardless of grade. Further advances in systemic therapies are needed to improve the outcomes of advanced disease.