Risk Of Mortality In Cancer Patients Research Articles

Comprehensive pan-cancer analysis of mitochondrial outer membrane permeabilisation activity reveals positive immunomodulation and assists in identifying potential therapeutic targets for immunotherapy resistance.

Mitochondrial outer membrane permeabilisation (MOMP) plays a pivotal role in cellular death and immune activation. A deeper understanding of the impact of tumour MOMP on immunity will aid in guiding more effective immunotherapeutic strategies. A comprehensive pan-cancer dataset comprising 30 cancer-type transcriptomic cohorts, 20 immunotherapy transcriptomic cohorts and three immunotherapy scRNA-seq datasets was collected and analysed to determine the influence of tumour MOMP activity on clinical prognosis, immune infiltration and immunotherapy effectiveness. Leveraging 65 scRNA-Seq datasets, the MOMP signature (MOMP.Sig) was developed to accurately reflect tumour MOMP activity. The clinical predictive value of MOMP.Sig was explored through machine learning models. Integration of the MOMP.Sig model and a pan-cancer immunotherapy CRISPR screen further investigated potential targets to overcome immunotherapy resistance, which subsequently underwent clinical validation. Our research revealed that elevated MOMP activity reduces mortality risk in cancer patients, drives the formation of an anti-tumour immune environment and enhances the response to immunotherapy. This finding emphasises the potential clinical application value of MOMP activity in immunotherapy. MOMP.Sig, offering a more precise indicator of tumour cell MOMP activity, demonstrated outstanding predictive efficacy in machine-learning models. Moreover, with the assistance of the MOMP.Sig model, FOXO1 was identified as a core modulator that promotes immune resistance. Finally, these findings were successfully validated in clinical immunotherapy cohorts of skin cutaneous melanoma and triple-negative breast cancer patients. This study enhances our understanding of MOMP activity in immune modulation, providing valuable insights for more effective immunotherapeutic strategies across diverse tumours.

Abstract B043: Challenges in managing cancer patients with congenital coronary artery anomalies: A case report

Abstract Introduction: Congenital coronary artery anomalies are rare cardiac abnormalities that can increase the risk of sudden cardiac death, particularly during exercise. Patients with cancer and concurrent coronary artery disease face higher mortality risks, as they often receive delayed percutaneous coronary intervention. Additionally, anthracycline chemotherapy, commonly used in cancer treatment, can cause cardiotoxicity and worsen pre-existing cardiac abnormalities. Despite the complexity of managing cancer patients with coronary artery anomalies, there is a lack of clear guidelines and consensus on optimal approaches. This report presents a unique case of a patient with a malignant inter-arterial course of the right coronary artery and newly diagnosed Human T-lymphotropic virus type I-associated adult T-cell leukemia/lymphoma, discussing the challenges and implications of chemotherapy in such cases. Case Presentation: A 38-year-old male presented with weakness and palpitations, exhibiting abnormal laboratory findings. CT angiography revealed a malignant inter-arterial course of the right coronary artery with severe narrowing. Electrocardiograms showed ST elevations and subsequent T-wave inversions. Despite the increased risk of cardiomyopathy due to the coronary anomaly, the patient required chemotherapy for life-threatening tumor lysis syndrome and refractory lactic acidosis. Anthracycline-based chemotherapy was initiated, and a follow-up echocardiogram after six months showed no acute changes. Conclusion: Managing cancer patients receiving anthracycline chemotherapy remains challenging due to limited guidelines. Anthracycline-induced cardiotoxicity is a concern, especially in patients with pre-existing cardiac anomalies like the malignant inter-arterial course of the right coronary artery. This case emphasizes the importance of recognizing and managing such anomalies in cancer patients to reduce the risk of sudden cardiac death. The higher mortality risk in cancer patients with coronary artery disease highlights the need for guidelines in managing anomalous coronary vessels in cancer patients. Further research is necessary to develop evidence-based strategies for managing cardiac complications in cancer patients, particularly those with pre-existing cardiac anomalies. Citation Format: Aliya M. Khan, Sophia Navajas Urisote, Danish A. Sheikh. Challenges in managing cancer patients with congenital coronary artery anomalies: A case report [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B043.

Machine learning for longitudinal mortality risk prediction in patients with malignant neoplasm in São Paulo, Brazil

Artificial intelligence is becoming an important diagnostic and prognostic tool in recent years, as machine learning algorithms have been shown to improve clinical decision-making. These algorithms will have some of their most important applications in developing regions with restricted data collection, but their performance under this condition is still widely unknown. We analyzed longitudinal data from São Paulo, Brazil, to develop machine learning algorithms to predict the risk of death in patients with cancer. We tested different algorithms using nine separate model structures. Considering the area under the ROC curve (AUC-ROC), we obtained values of 0.946 for the general model, 0.945 for the model with the five main cancers, 0.899 for bronchial and lung cancer, 0.947 for breast cancer, 0.866 for stomach cancer, 0.872 for colon cancer, 0.923 for rectum cancer, 0.955 for prostate cancer, and 0.917 for uterine cervix cancer. Our results indicate the potential of building models for predicting mortality risk in cancer patients in developing regions using only routinely-collected data.

Assessment of Clinical Indicators Registered on Admission to the Hospital Related to Mortality Risk in Cancer Patients with COVID-19.

Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital and the risk of later death in cancer patients with COVID-19. The study included patients with a reported history of malignant tumor (n = 151) and a control group with no history of cancer (n = 151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models. Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients' admission were linked to significantly increased risk of death. They are: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophils. Early identification of the indicators of a poorer prognosis may serve clinicians in better tailoring surveillance or treatment among cancer patients with COVID-19.

Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study.

BackgroundCancer‐associated cachexia (CAC) is a complex syndrome of progressive muscle wasting and adipose loss with metabolic dysfunction, severely increasing the morbidity and mortality risk in cancer patients. However, there are limited studies focused on the underlying mechanisms of the progression of CAC due to the complexity of this syndrome and the lack of preclinical models that mimics its stagewise progression.MethodsWe characterized the initiation and progression of CAC in transgenic female mice with ovarian tumours. We measured proposed CAC biomarkers (activin A, GDF15, IL‐6, IL‐1β, and TNF‐α) in sera (n = 6) of this mouse model. The changes of activin A and GDF15 (n = 6) were correlated with the decline of bodyweight over time. Morphometry and signalling markers of muscle atrophy (n ≥ 6) and adipose tissue wasting (n ≥ 7) were assessed during CAC progression.ResultsCancer‐associated cachexia symptoms of the transgenic mice model used in this study mimic the progression of CAC seen in humans, including drastic body weight loss, skeletal muscle atrophy, and adipose tissue wasting. Serum levels of two cachexia biomarkers, activin A and GDF15, increased significantly during cachexia progression (76‐folds and 10‐folds, respectively). Overactivation of proteolytic activity was detected in skeletal muscle through up‐regulating muscle‐specific E3 ligases Atrogin‐1 and Murf‐1 (16‐folds and 14‐folds, respectively) with decreasing cross‐sectional area of muscle fibres (P < 0.001). Muscle wasting mechanisms related with p‐p38 MAPK, FOXO3, and p‐AMPKα were highly activated in concurrence with an elevation in serum activin A. Dramatic fat loss was also observed in this mouse model with decreased fat mass (n ≥ 6) and white adipocytes sizes (n = 6) (P < 0.0001). The adipose tissue wasting was based on thermogenesis, supported by the up‐regulation of uncoupling protein 1 (UCP1). Fibrosis in adipose tissue was also observed in concurrence with adipose tissue loss (n ≥ 13) (p < 0.0001).ConclusionsOur novel preclinical CAC mouse model mimics human CAC phenotypes and serum biomarkers. The mouse model in this study showed proteolysis in muscle atrophy, browning in adipose tissue wasting, elevation of serum activin A and GDF15, and atrophy of pancreas and liver. This mouse line would be the best preclinical model to aid in clarifying molecular mediators of CAC and dissecting metabolic dysfunction and tissue atrophy during the progression of CAC.

Short- and Long-Term Mortality Prediction in Critically Ill Cancer Patients Admitted to the Intensive Care Unit (CanICU) Using Machine Learning

Background: Although cancer patients are increasingly admitted to the intensive care unit (ICU) for cancer- or treatment-related complications, improved mortality prediction remains a big challenge. Current prognostic models for a general ICU population underestimate the mortality risk in cancer patients. Methods: We developed CanICU, a machine learning-based 28-day and 1-year mortality prediction program in adult cancer patients admitted to ICU from Medical Information Mart for Intensive Care (MIMIC) database in the USA (n=766), Yonsei Cancer Center (YCC, n=3,571), and Samsung Medical Center in Korea (SMC, n=2,563). We constructed the classifier and compared it with a general prognostic model. Findings: A total of 6,900 patients were included, with a 28-day mortality of 10.2%/12.7%/36.6% and 1-year mortality of 30.0%/31.4%/58.5% in the MIMIC, YCC, and SMC cohort, respectively. Nine clinical and laboratory factors were used to construct the classifier using a random forest machine-learning algorithm. CanICU had the area under the receiver operating characteristic (AUROC) of 0.95 (95% CI 0.93-0.97) for 28-day and 0.79 (95% CI 0.76-0.82) for 1-year mortality, showing better performance than a current prognostic model (Sequential Organ Failure Assessment [SOFA], 0.77 [95% CI 0.72-0.81] for 28-day and 0.67 [95% CI 0.64-0.70] for 1-year mortality). Application of CanICU in external data sets across the countries yielded better AUROC for 28-day mortality than SOFA (95% CI, 0.75-0.80 vs. 0.57-0.63 with SOFA in SMC; 95% CI, 0.72-0.79 vs. 0.64-0.72 with SOFA in MIMIC). Interpretation: CanICU offers improved performance for predicting short- and long-term mortality in critically ill cancer patients admitted to ICU. A user-friendly online implementation is available and should be valuable for better mortality risk stratification. This might help physicians to determine to allocate ICU care for patients with cancer. Funding Information: This study was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2019R1C1C1006709, 018R1A5A2025079, 2020M3F7A1094093), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, the Republic of Korea (No. KHIDIHI19C1015010020), and was also supported by the ational R&D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health & Welfare, Republic of Korea (HA21C0065). Declaration of Interests: The authors have no potential conflicts of interest to disclose. Ethics Approval Statement: The institutional review boards of all participating hospitals approved this study and waived the requirement for informed consent because of the observational nature of the research. All patient records and data were anonymized and de-identified before analysis.

Rural residence is related to shorter survival in epithelial ovarian cancer patients

ObjectiveRural residence has been related to health disparities and greater mortality risk in cancer patients, including gynecologic cancer patients. Lower survival rates for rural cancer survivors have been attributed to limited access to specialized healthcare, including surgery. Here, we examined whether a rural/urban survival gap existed in ovarian cancer patients receiving surgery at tertiary-care facilities, and potential causes for this gap, including educational attainment. MethodsRural and urban patients with high grade invasive ovarian cancer (n = 342) seeking treatment at two midwestern tertiary-care university hospitals were recruited pre-surgery and followed until death or censoring date. Rural/urban residence was categorized using the USDA Rural-Urban Continuum Codes. Stratified Cox proportional hazards regression analyses, with clinical site as strata, adjusting for clinical and demographic covariates, were used to examine the effect of rurality on survival. ResultsDespite specialized surgical care, rural cancer survivors showed a higher likelihood of death compared to their urban counterparts, HR = 1.39 (95% CI: 1.04, 1.85) p = 0.026, adjusted for covariates. A rurality by education interaction was observed (p = 0.027), indicating significantly poorer survival in rural vs. urban patients among those with trade school/some college education, adjusted HR = 2.49 (95% CI: 1.44, 4.30), p = 0.001; there was no rurality survival disparity for the other 2 levels of education. ConclusionsDifferences in ovarian cancer survival are impacted by rurality, which is moderated by educational attainment even in patients receiving initial care in tertiary settings. Clinicians should be aware of rurality and education as potential risk factors for adverse outcomes and develop approaches to address these possible risks.

Presepsin in the Rapid Response System for Cancer Patients: A Retrospective Analysis.

Introduction: Early diagnosis of sepsis is paramount to effective management. The present study aimed to compare the prognostic accuracy of presepsin levels and other biomarkers in the assessment of septic shock and mortality risk in cancer patients. Materials and methods: A total of 74 cancer patients were evaluated for presepsin, lactic acid, C-reactive protein (CRP) levels, and white blood cell count (WBC). Specificity and sensitivity values for septic shock and death were compared between four biomarkers in all patients and those with and without acute kidney injury (AKI). Results: A total of 27 and 29 patients experienced septic shock and died, respectively. The area under the curve (AUC) and sensitivity and specificity estimated for presepsin levels for septic shock were 60%, 74%, and 51%, respectively. The corresponding values for mortality were 62%, 72%, and 49%, respectively. In patients without AKI, AUC of presepsin levels for septic shock and death were 62% and 65%, respectively; in those with AKI, these values were 44% and 58%, respectively. Presepsin levels showed higher sensitivity and specificity values than WBC and higher specificity than CRP but were similar to those of lactic acid levels. Conclusions: Presepsin levels are similar to lactic acid levels in the assessment of septic shock and mortality risk in cancer patients. In patients with AKI, presepsin levels should be considered carefully.

Impact of comorbidity assessment methods to predict non-cancer mortality risk in cancer patients: a retrospective observational study using the National Health Insurance Service claims-based data in Korea

BackgroundCancer patients’ prognoses are complicated by comorbidities. Prognostic prediction models with inappropriate comorbidity adjustments yield biased survival estimates. However, an appropriate claims-based comorbidity risk assessment method remains unclear. This study aimed to compare methods used to capture comorbidities from claims data and predict non-cancer mortality risks among cancer patients.MethodsData were obtained from the National Health Insurance Service-National Sample Cohort database in Korea; 2979 cancer patients diagnosed in 2006 were considered. Claims-based Charlson Comorbidity Index was evaluated according to the various assessment methods: different periods in washout window, lookback, and claim types. The prevalence of comorbidities and associated non-cancer mortality risks were compared. The Cox proportional hazards models considering left-truncation were used to estimate the non-cancer mortality risks.ResultsThe prevalence of peptic ulcer, the most common comorbidity, ranged from 1.5 to 31.0%, and the proportion of patients with ≥1 comorbidity ranged from 4.5 to 58.4%, depending on the assessment methods. Outpatient claims captured 96.9% of patients with chronic obstructive pulmonary disease; however, they captured only 65.2% of patients with myocardial infarction. The different assessment methods affected non-cancer mortality risks; for example, the hazard ratios for patients with moderate comorbidity (CCI 3–4) varied from 1.0 (95% CI: 0.6–1.6) to 5.0 (95% CI: 2.7–9.3). Inpatient claims resulted in relatively higher estimates reflective of disease severity.ConclusionsThe prevalence of comorbidities and associated non-cancer mortality risks varied considerably by the assessment methods. Researchers should understand the complexity of comorbidity assessments in claims-based risk assessment and select an optimal approach.

SARS-CoV-2 Positive Hospitalized Cancer Patients during the Italian Outbreak: The Cohort Study in Reggio Emilia.

In the coronavirus disease (COVID-19) pandemic, cancer patients could be a high-risk group due to their immunosuppressed status; therefore, data on cancer patients must be available in order to consider the most adequate strategy of care. We carried out a cohort study on the risk of hospitalization for COVID-19, oncological history, and outcomes on COVID-19 infected cancer patients admitted to the Hospital of Reggio Emilia. Between 1 February and 3 April 2020, a total of 1226 COVID-19 infected patients were hospitalized. The number of cancer patients hospitalized with COVID-19 infection was 138 (11.3%). The median age was slightly higher in patients with cancers than in those without (76.5 vs. 73.0). The risk of intensive care unit (ICU) admission (10.1% vs. 6.7%; RR 1.23, 95% Confidence Interval (CI) 0.63–2.41) and risk of death (34.1% vs. 26.0%; RR 1.07, 95% CI 0.61–1.71) were similar in cancer and non-cancer patients. In the cancer patients group, 89/138 (64.5%) patients had a time interval >5 years between the diagnosis of the tumor and hospitalization. Male gender, age > 74 years, metastatic disease, bladder cancer, and cardiovascular disease were associated with mortality risk in cancer patients. In the Reggio Emilia Study, the incidence of hospitalization for COVID-19 in people with previous diagnosis of cancer is similar to that in the general population (standardized incidence ratio 98; 95% CI 73–131), and it does not appear to have a more severe course or a higher mortality rate than patients without cancer. The phase II of the COVID-19 epidemic in cancer patients needs a strategy to reduce the likelihood of infection and identify the vulnerable population, both in patients with active antineoplastic treatment and in survivors with frequently different coexisting medical conditions.

MON-008 Use of National Death Index to Assess Cancer Mortality and Diabetes Relationship

Background: We have previously examined the link between diabetes mellitus (DM) and malignancy with respect to glycemic control and survival. Given that mortality data derived from our own records is limited, and to better determine if DM changes mortality risk in cancer patients with co-existing DM, we linked our clinical records with the National Death Index (NDI), housed and maintained by the Centers for Disease Control and Prevention. Objective: The primary objective of this study was to evaluate the risk DM imposes on mortality in cancer patients via the National Death Index. The secondary objective was to ascertain the cause of death in cancer patients with and without DM. Methods: We identified 1565 patients with newly diagnosed prostate, breast, lung, colorectal, and pancreatic cancer from the institutional cancer registry from 2010-2015. This data was forwarded to the CDC/NDI for input on whether each patient was alive or deceased, and cause of death (if applicable). NDI records were reviewed and verified with a resulting data set containing 1404 patients, matched 2:1; cancer without DM (n=936) and cancer and concurrent DM patients (n=468). Patients were matched by year of diagnosis, age, gender, and cancer type. Primary cause of death was categorized into cancer-related, vascular, non-cancer/non-vascular, and unknown. Five-year survival was estimated with the Kaplan-Meier method and Cox proportional hazards regression analysis was used with the matched pair as the strata variable. Results: Distribution of cancer types was: prostate (43%), lung (19%), breast (15%), colorectal (12%) and pancreatic (11%). Mean (SD) age at diagnosis was 68 (10) years; 70% of patients were male. There were 435 deaths with 168 deaths (36%) in the DM cohort and 267 (29%) in the non-DM cohort. Median follow-up was 47.3 (0.5-94.1) months across all cancer types. Overall 5-year survival was estimated at 59% (95% CI: 54-64%) for DM patients versus 67% (95% CI: 64-71%) in non-DM patients. Matched pairs Cox regression was HR= 1.35; 95% CI 1.02-1.79; p =0.04. There were 134 cancer related deaths (79%) in the DM cohort, and 233 (87%) in the non-DM cohort. There were 26 non-cancer, non-vascular deaths (15% in the DM cohort, and 13 (5%) in the non-DM cohort (p<0.001). Conclusions: Overall there is an increased risk of death for DM vs non-DM patients who have cancer. There is a higher proportion of non-cancer, non-vascular deaths in DM patients than in non-DM patients.

Individualized estimates of overall survival in radiation therapy plan optimization - A concept study.

Current radiation therapy planning uses a set of defined dose-volume constraints to ensure a specified level of tumor coverage while constraining the dose distribution in the organs at risk. Such constraints are aggregated, population-based quantities that do not adequately consider patient-specific risk factors. Furthermore, these constraints are calculated for each organ independently and it is therefore not guaranteed that the optimal trade-off between organs is achieved. We introduce a novel radiotherapy planning approach where a patient-specific all-cause mortality risk is minimized using inverse plan optimization. As illustration of concept, our outcome risk model incorporates patient age, sex, cardiac risk factor (CRF), and smoking. We retrospectively analyzed a left-sided breast cancer case and a Hodgkin's lymphoma case, both clinically treated with three-dimensional conformal radiotherapy (3D-CRT). Our objective function for inverse plan optimization was an equally weighted summation of risk models for cancer recurrence and mortality from radiation-induced coronary heart disease and secondary lung and breast cancers incorporating patient age, sex, CRF, and smoking. We allowed the optimization algorithm to choose from a large set of gantry angles. The optimization task was to choose beams and optimize monitor units (MUs) so that overall survival was maximized (and the total risk of cancer recurrence and mortality from radiation-induced causes were minimized). The sensitivity analysis was performed in the lymphoma case by changing the tumor control probability model from using mean dose (Model 1) to using generalized equivalent uniform dose (Model 2). For the breast case in this study, the 3D-CRT clinical plan used eight beams while the proposed 3D-CRT outcome-optimized plan used five beams, reducing the total risk - summation of the risks of recurrence and secondary disease mortality - from 3% to 2%. The mean doses to clinical target volume (CTV) and internal mammary nodes (IMN) were increased in the outcome-optimized plan by 1.9 and 1.8Gy, respectively. For the Hodgkin's lymphoma case, the clinical 3D-CRT plan used two beams, while the proposed 3D-CRT outcome-optimized plan used three beams, reducing the total risk by 6% (from 16% to 10%). Using either of the two tumor control models for the lymphoma case resulted in outcome-optimized plans where tumor control was compensated at the cost of saving organs at risk. However, the impact of sensitivity to models was comparatively large. Using Model 1 resulted in a reduction in mean target dose by 15.2 vs 7.1Gy for Model 2. In all cases, the chosen beams in outcome-optimized plans were different from clinically used beams. The proposed optimization strategy, supplanting dosimetric objectives with comprehensive individual risk estimates, has the potential to yield improved outcomes in terms of reduced mortality risk in cancer patients treated with radiotherapy. The approach is, however, currently limited by gaps in knowledge about the effect of compromising dose to part of the target, for example, in order to spare cardiac structures.

The Plausibility of Obesity Paradox in Cancer-Point.

In contrast to the convincing evidence that obesity (measured by body mass index, BMI) increases the risk of many different types of cancer, there is an ambiguity in the role of obesity in survival among cancer patients. Some studies suggested that higher BMI decreased mortality risk in cancer patients, a phenomenon called the obesity paradox. The spurious positive association between BMI and cancer survival is likely to be explained by several methodologic limitations including confounding, reverse causation, and collider stratification bias. Also, the inadequacy of BMI as a measure of body fatness in cancer patients commonly experiencing changes in body weight and body composition may have resulted in the paradox. Other factors contributing to the divergent results in literature are significant heterogeneity in study design and method (e.g., study population, follow-up length); time of BMI assessment (pre-, peri-, or post-diagnosis); and lack of consideration for variability in the strength and directions of associations by age, sex, race/ethnicity, and cancer subtype. Robust but practical methods to accurately assess body fatness and body compositions and weight trajectories in cancer survivors are needed to advance this emerging field and to develop weight guidelines to improve both the length and the quality of cancer survival. Cancer Res; 78(8); 1898-903. ©2018 AACR.

Unprovoked venous thromboembolism and subsequent cancer risk: a population‐based cohort study

ESSENTIALS: A relationship between unprovoked venous thromboembolism (VTE) and cancer risk was investigated. We collected 27,751 VTE patients and compared them with 110,409 frequency-matched people without VTE. This cohort study showed significantly higher risks of overall and site-specific cancers in the VTE group. There is an increased risk in the first 6 months after VTE, and VTE can be an indicator of occult cancer. We investigated the relationship between unprovoked venous thromboembolism (VTE) and subsequent cancer risk in Taiwan, focusing on both short-term and long-term cancer development. For the case group, we obtained data on 27,751 patients diagnosed with unprovoked VTE between 1 January 1998, and 31 December 2008. For the comparison group, four people without unprovoked VTE were frequency-matched with each unprovoked VTE patient according to age, sex, and index year. Cox proportional hazards regression models were employed to determine the effects of unprovoked VTE on cancer risk. Overall cancer risk was significantly higher in the unprovoked VTE group than in the comparison group (adjusted hazard ratio = 2.26, 95% confidence interval = 2.16-2.37). The increased risk was observed in both men and women in various age groups. The patients in the unprovoked VTE group showed a significantly increased risk of cancer at all site-specific cancer sites. Analyses stratified according to follow-up duration revealed that significant differences were more evident between the two groups over a follow-up duration of < 0.5 years than over a follow-up duration of ≥ 3 years. Furthermore, the 1-year mortality risk of cancer patients with unprovoked VTE was significantly higher than that for cancer patients in the non-VTE group. The results of this study show that unprovoked VTE is associated with a consistently high risk of subsequent cancer diagnosis. This is particularly true in the first 6 months after VTE. It suggests that unprovoked VTE can be an indicator of occult malignancy.

Low molecular weight heparin and cancer survival: clinical trials and experimental mechanisms.

The relationship between cancer and thrombosis is complex, as the hemostatic system is inextricably linked to the mechanisms of cancer growth and metastasis. The coagulation system thus appears to be a site for oncogenic events and necessary for the survival and spread of malignant cells. Although several meta-analyses on the effectiveness of unfractionated heparin and low molecular weight heparin (LMWH) in the treatment of venous thromboembolism (VTE) have suggested a lower mortality risk in cancer patients receiving LMWH, this contention has not received general acceptance. In fact, there exist no sufficiently powered studies to date supporting the routine use of LMWH to improve cancer survival. Meanwhile, the molecular mechanism underlying the anti-neoplastic effect of LMWH which is independent of its anti-coagulant function is largely unexplored and is a topic of active investigation. In this communication, we aimed to review comprehensively evidences from clinical trials, meta-analysis as well as experimental molecular research and to identify future research areas of importance so as to stimulate future research on the potential anti-tumor action of LMWH. Although benefit of LMWH on cancer patients' survival is controversial depending on the tumor type, cancer stage as well as LMWH type, it appears to be associated with a reduction in VTE and increased bleeding is minor and controllable; thus, randomized controlled trials targeting the survival benefit of certain specific LWMH are needed and justified, and more in-depth experimental researches are imperative to elucidate the anti-tumor effect of anticoagulants.

Life expectancy of colon, breast, and testicular cancer patients: an analysis of US-SEER population-based data

Cancer survivorship is an increasingly important issue in cancer control. Life expectancy of patients diagnosed with breast, colon, and testicular cancers, stratified by age at diagnosis and time since diagnosis, is provided as an indicator to evaluate future mortality risks and health care needs of cancer survivors. The standard period life table methodology was applied to estimate excess mortality risk for cancer patients diagnosed in 1985-2011 from SEER registries and mortality data of the general US population. The sensitivity of life expectancy estimates on different assumptions was evaluated. Younger patients with colon cancer showed wider differences in life expectancy compared with that of the general population (11.2 years in women and 10.7 in men at age 45-49 years) than older patients (6.3 and 5.8 at age 60-64 years, respectively). Life expectancy progressively increases in patients surviving the first years, up to 4 years from diagnosis, and then starts to decrease again, approaching that of the general population. For breast cancer, the initial drop in life expectancy is less marked, and again with wider differences in younger patients, varying from 8.7 at age 40-44 years to 2.4 at ages 70-74 years. After diagnosis, life expectancy still decreases with time, but less than that in the general population, slowly approaching that of cancer-free women. Life expectancy of men diagnosed with testicular cancer at age 30 years is estimated as 45.2 years, 2 years less than cancer-free men of the same age. The difference becomes 1.3 years for patients surviving the first year, and then slowly approaches zero with increasing survival time. Life expectancy provides meaningful information on cancer patients, and can help in assessing when a cancer survivor can be considered as cured.

Risk of Cancer in Diabetes: The Effect of Metformin

Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge.

High D-dimer levels are associated with poor prognosis in cancer patients

Systemic activation of hemostasis is frequently observed in cancer patients, even in the absence of thrombosis. Moreover, this activation has been implicated in tumor progression, angiogenesis and metastatic spread. Increased levels of D-dimer, which is a degradation product of cross-linked fibrin, indicate a global activation of hemostasis and fibrinolysis. In a prospective and observational cohort study, we assessed the prognostic value of D-dimer levels for overall survival and mortality risk in 1178 cancer patients included in the Vienna Cancer and Thrombosis Study (CATS). Patients were followed over 2 years at regular intervals until occurrence of symptomatic venous thromboembolism or death. D-dimer levels were measured with a quantitative D-dimer latex agglutination assay The main solid tumors were malignancies of the lung (n=182), breast (n=157), lower gastrointestinal tract (n=133), pancreas (n=74), stomach (n=50), kidney (n=37), prostate (n=133), and brain (n=148); 201 of the patients had hematologic malignancies; 63 had other tumors. During a median follow-up of 731 days, 460 (39.0%) patients died. The overall survival probabilities for patients with D-dimer levels categorized into four groups based on the 1(st), 2(nd) and 3(rd) quartiles of the D-dimer distribution in the total study population were 88%, 82%, 66% and 53% after 1 year, and 78%, 66%, 50% and 30% after 2 years, respectively (P<0.001). The univariate hazard ratio of D-dimer (per double increase) for mortality was 1.5 (95% confidence interval: 1.4-1.6, P<0.001) and remained increased in multivariable analysis including tumor subgroups, age, sex and venous thromboembolism. High D-dimer levels were associated with poor overall survival and increased mortality risk in cancer patients.

Clinical Outcomes and Prognostic Factors of Cancer Patients with Pyogenic Liver Abscess

PurposePyogenic liver abscess (PLA) of cancer patients often has a poor prognosis, but corresponding prognostic factors are less investigated. This study aimed to identify predictors of mortality in cancer patients with PLA. Patients and MethodsMedical records of 85 consecutive cancer patients (46 with hepatobiliary pancreatic cancer, 14 with gastrointestinal cancer, and 25 with non-digestive system cancer) having PLA who were admitted to two university hospitals were retrospectively reviewed. The predictors of mortality were determined using Cox regression model. ResultsThe overall case fatality rate was 33%. In multivariate analysis, the greater Acute Physiology and Chronic Health Evaluation II score (P = 0.028), multiloculated abscess (P = 0.025), and polymicrobial infection (P = 0.003) were associated with mortality. In subgroup analysis of the 25 patients with multiloculated abscess undergoing percutaneous catheter drainage as primary treatment, the case fatality rates of patients with a solitary smaller abscess (size < 5 cm), those with a solitary larger abscess (size > 5 cm), and those with larger multiple abscesses were 0%, 36%, and 85%, respectively (P = 0.002; using χ2 for trend). ConclusionsThe advanced disease stage, multiloculated abscess, and polymicrobial infection posed a greater mortality risk in cancer patients with PLA. Moreover, an early surgical approach should be considered for cancer patients having large, multiloculated complex PLAs.

D-dimer levels and prediction of overall survival in cancer patients.

10587 Background: Procoagulant changes in the haemostatic system and activation of haemostasis are frequently observed in cancer patients, even in the absence of venous thromboembolism (VTE). Moreover, coagulation activation has been implicated in tumour progression, invasion, angiogenesis and metastatic spread. D-dimer is produced when cross-linked fibrin is degraded by plasmin and reflects the activation of coagulation and fibrinolysis. Recently, high D-dimer levels were reported to predict the occurrence of VTE in cancer patients. Our aim was to assess the prognostic value of D-dimer levels in cancer patients included in the ongoing prospective observational Vienna Cancer and Thrombosis Study (CATS), which was initiated in 2003 to identify predictive parameters for cancer-associated VTE. Methods: The CATS includes patients with newly diagnosed cancer or progression of disease after remission. Patients are followed over 2 years at regular intervals until occurrence of symptomatic VTE or death. D-dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan-Meier and Cox regression analyses were applied for statistical calculation. Results: Data from 873 patients with solid tumours or haematological malignancies (394 female/479 male, median age [IQR]: 62 [53-68] yrs) were available for survival analyses. Main tumor entities were malignancies of the breast (n = 139), lung (n = 126), stomach (n = 36), lower gastrointestinal tract (n = 114), pancreas (n = 48), kidney (n = 24), prostate (n = 113), and brain (n = 109); 116 had hematologic malignancies; 48 had other tumors. Patients were followed for a median observation time of 731 days and 357 (40.1%) patients died during follow-up. The probabilities of overall survival for patients with D-Dimer levels at study inclusion in the first, second, third and fourth quartile were 88%, 82%, 66% and 53% after 1 year and 80%, 66%, 50% and 30% after 2 years, respectively (p < 0.001). The hazard ratio (HR) of D- dimer for mortality was 1.5 (95% CI: 1.4-1.6, p < 0.001) per double increase of D-dimer and remained similarly increased in multivariable analysis which included age, sex and metastatic spread. Conclusions: High levels of D-dimer independently predict mortality risk in cancer patients. No significant financial relationships to disclose.