5-year Survivors Research Articles

Association between physical activity and subsequent cardiovascular disease among 5-year breast cancer survivors.

To examine the association of physical activity among long-term breast cancer survivors on the occurrence of subsequent cardiovascular disease (CVD). We investigated the risk of CVD among 39,775 breast cancer patients who were newly diagnosed in 2006 and survived until 2011 within the Korean National Health Insurance Service database. Patients were followed up from 5years after breast cancer diagnosis to the date of CVD event, death, or December 31, 2018, whichever came earliest. Every 500 MET-mins/week correspond to 152, 125, and 62.5min per week of light-, moderate-, and vigorous-intensity physical activity, respectively. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated using Cox proportional hazards regression by physical activity levels. Compared with those with physical activity of 0 MET-min/week, those with 1-499 (aHR 0.82, 95% CI 0.69-0.98), 500-999 (aHR 0.75, 95% CI 0.63-0.90), and ≥ 1,000 (aHR 0.76, 95% CI 0.63-0.93) MET-min/week of PA had lower risk of CVD. Higher levels of PA were associated with lower risk of stroke (p for trend = 0.016). The benefits of PA on obese and overweight breast cancer survivors were smaller than those in normal weight survivors. The frequency of moderate-to-vigorous physical activity (MVPA) showed a reverse J-curve association with CVD, and the best benefit occurred in the 3-4 times MVPA per week group (aHR 0.59, 95% CI 0.46-0.74). The study showed that even small amounts of PA may be beneficial in potentially decreasing the risk of CVD, CHD, and stroke in breast cancer survivors. Our result will be useful to prescribe and delivery exercise among long-term breast cancer survivors.

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

STUDY QUESTIONDo genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?SUMMARY ANSWERFemale CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.WHAT IS KNOWN ALREADYFemale CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.STUDY DESIGN, SIZE, DURATIONCCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391).PARTICIPANTS/MATERIALS, SETTING, METHODSTo evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis.MAIN RESULTS AND THE ROLE OF CHANCEMeta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10−4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00).LIMITATIONS, REASONS FOR CAUTIONWhile low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function.WIDER IMPLICATIONS OF THE FINDINGSFurther research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A.

Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation

BackgroundWhether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain. ObjectivesThe goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery. MethodsPatients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years. ResultsPatients’ mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04). ConclusionsAfter IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart’s Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040)

Rare case of BRAF V600E mutant anaplastic pleomorphic xanthroastrocytoma in a 5-year survivor of acute lymphoblastic leukaemia

A 20-year-old woman with a history of acute lymphoblastic leukaemia treated at 13 years old with radiation and chemotherapy and a benign cystic mature ovarian teratoma diagnosed at 18 years...

Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort.

Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up. We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined. Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder-associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04). Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder-associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.

Disease-specific hospitalizations among 5-year survivors of Wilms tumor: A Nordic population-based cohort study.

With modern therapy, over 90% of Wilms tumor patients can expect to become long-term survivors, and focus on morbidity and late effects become increasingly important. We provide a novel evaluation and insight to subsequent hospitalizations in 5-year survivors of Wilms tumor. As part of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study, we identified 5-year survivors of Wilms tumor. Based on stratified random sampling, we constructed a population comparison cohort. Outcomes of interest were overall hospitalizations; hospitalizations for specific organ systems and disease-specific categories. Standardized hospitalization rate ratios (SHRR) and absolute excess risks (AER) were calculated. We included 913, 5-year survivors of Wilms tumor and 152231 population comparisons. Survivors of Wilms tumor had an increased overall risk of being hospitalized (SHRR 1.8; 95% confidence interval (CI) 1.7-2.0). The hospitalization risk was increased within all major organ systems: urinary and genital organs (SHRR 2.5; 95% CI 2.1-3.0), endocrine (SHRR 2.5; 95% CI 1.9-3.3), cardiovascular (SHRR 2.2; 95% CI 1.7-2.9), and gastrointestinal (SHRR 1.5; 95% CI 1.3-1.8). Risks for specific diseases are reported in the study. Survivors of Wilms tumor had higher risks than population comparisons for a wide range of diseases, with the highest risks seen for urinary, endocrine, and cardiovascular disorders. Five to 20years after the Wilms tumor diagnosis, 43% of survivors had been hospitalized at least once versus 29% of population comparisons. The overall AER was 2.3, which translates into 0.2 extra hospitalizations in 10years for every Wilms tumor survivor.

Female reproductive function after treatment of childhood acute lymphoblastic leukemia.

The aim was to evaluate self-reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. Self-reported reproductive characteristics were assessed by questionnaire among 357 adult 5-year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]-only group, CT and radiotherapy [RT] group) were analyzed. Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P<.01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1-0.6], 0.5 [0.3-0.9], and 0.4 [0.2-0.9], respectively). Survivors in the CT-only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function. Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.

Development and validation of a novel nomogram predicting 10-year actual survival after curative hepatectomy for hepatocellular carcinoma

IntroductionAlthough hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), the associated 10-year long-term actual survival are rarely reported. This study aims to develop and validate a predictive nomogram for 10-year actual survivors with HCC. Materials and methodsFrom 2004 to 2009, 753 patients with curative hepatectomy for HCC (development set, n = 325; validation set, n = 428) were included. In development set, comparison of clinic-pathological data was made between patients surviving ≥10 years and those surviving <10 years. Good independent prognostic factors identified by multivariate analysis were involved in a nomogram development, which was validated internally and externally using validation set. ResultsOn multivariate analysis, five independent good prognostic factors for 10-year survival were identified, including young age (OR = 0.943), good ASA status (≤2) (OR = 2.794), higher albumin level (OR = 1.116), solitary tumor (OR = 2.531) and absence of microvascular invasion (OR = 3.367). A novel nomogram was constructed with C-index of 0.801 (95% CI 0.762–0.864). A cut-off point of 167.5 had a sensitivity of 0.794 and specificity of 0.730. Internal validation using bootstrap sampling and external validation using validation set revealed C-index of 0.792 (95% CI, 0.741–0.853) and 0.761 (95% CI, 0.718–0.817). ConclusionA novel nomogram for 10-year HCC survivor using age, ASA status, preoperative albumin, tumor number and presence of microvascular tumor invasion was developed and validated with high accuracy.

Physical fitness and modifiable cardiovascular disease risk factors in survivors of childhood cancer: A report from the SURfit study.

Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors. The authors analyzed cross-sectional data from ≥5-year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high-density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1-minute sit-to-stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy. This study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome. Better aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance. This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease. Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors. This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease.

Fine Particulate Matter Air Pollution and Mortality Risk Among US Cancer Patients and Survivors.

BackgroundExposure to fine particulate matter (PM2.5) air pollution has been linked to increased risk of mortality, especially cardiopulmonary and lung cancer mortality. It is unknown if cancer patients and survivors are especially vulnerable to PM2.5 air pollution exposure. This study evaluates PM2.5 exposure and risk for cancer and cardiopulmonary mortality in cohorts of US cancer patients and survivors.MethodsA primary cohort of 5 591 168 of cancer patients and a 5-year survivor cohort of 2 318 068 was constructed using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, linked with county-level estimates of long-term average concentrations of PM2.5. Cox proportional hazards models were used to estimate PM2.5-mortality hazard ratios controlling for age-sex-race combinations and individual and county-level covariables.ResultsOf those who died, 26% died of noncancer causes, mostly from cardiopulmonary disease. Minimal PM2.5-mortality associations were observed for all-cause mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00 to 1.03) per 10 µg/m3 increase in PM2.5. Substantial adverse PM2.5-mortality associations were observed for cardiovascular (HR = 1.32, 95% CI = 1.26 to 1.39), chronic obstructive pulmonary disease (HR = 1.10, 95% CI = 1.01 to 1.20), influenza and pneumonia (HR = 1.55, 95% CI = 1.33 to 1.80), and cardiopulmonary mortality combined (HR = 1.25, 95% CI = 1.21 to 1.30). PM2.5-cardiopulmonary mortality hazard ratio was higher for cancer patients who received chemotherapy or radiation treatments.ConclusionsAir pollution is adversely associated with cardiopulmonary mortality for cancer patients and survivors, especially those who received chemotherapy or radiation treatment. Given ubiquitous and involuntary air pollution exposures and large numbers of cancer patients and survivors, these results are of substantial clinical and public health importance.

Actual long-term survival after resection of stage III soft tissue sarcoma

BackgroundActuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS.MethodsWe retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years.ResultsMultivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95, p = 0.047], histological grade of 2 (OR 8.12, p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25, p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival.ConclusionsActual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.

Development of Nomogram Predicting 10-Year Survivors after Curative Hepatectomy for Hepatocellular Carcinoma

Background: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), clinical outcome and predictive factors of 10-year long-term survivors are rarely reported in the literature. Aim of study: To analyze the clinico-pathological factors of 10-year long-term survivors following curative hepatectomy for HCC and to develop a predictive nomogram for 10-year survivors. Methods: From 2004 to 2009, 325 patients with HCC underwent curative hepatectomy. There were 95 patients (29.2%) surviving 10 years or more (group 1), whereas 230 patients (70.8%) surviving < 10 years (group 2). Comparison of clinic-pathological data was made between two groups. Good prognostic factors identified by multivariate analysis were used to construct a nomogram predicting 10-year survivors. Internal validation using bootstrap sampling was also performed. Results: Group 1 was younger, had more asymptomatic tumor, had more hepatitis B carriers, better functional status, better preoperative liver function, and higher albumin level, compared with group 2. Group 1 had smaller tumor, more solitary tumor, more tumor with microvascular invasion and rupture than Group 2. Independent good prognostic factors predicting 10-year survivor were young age, ASA status (≤ 2), high albumin, solitary tumor and no microvascular tumor invasion. A nomogram is constructed (Figure 1) with C-index of 0.801. Internal validation using bootstrap sampling reveals C-index of 0.792. Conclusion: There are 29.2% patients with curative hepatectomy for HCC can survive up to or more than 10 years. Nomogram using age, ASA status, preoperative albumin, solitary tumor and microvascular tumor invasion can accurately predict 10-year survivor.

The Incidence of Breast Cancer Recurrence 10-32 Years After Primary Diagnosis

Background: Extended, more effective breast cancer (BC) treatments have increased the prevalence of long term survivors. We investigated the risk of late breast cancer recurrence (BCR), 10 years or more after primary diagnosis, and associations between patient and tumor characteristics at primary diagnosis and late BCR up to 32 years after primary BC diagnosis. Methods: Using the Danish Breast Cancer Group clinical database, we identified all women with an incident early (non-distant metastatic) BC diagnosed during 1987–2004. We restricted to women who survived 10 years without a recurrence or second cancer (10-year disease-free survivors) and followed them from 10 years after BC diagnosis date until death, emigration, second cancer, or December 31, 2018. We calculated incidence rates (IRs) per 1,000 person-years and cumulative incidences for late BCR, stratifying by follow-up time, patient- and tumor characteristics. Using Cox regression, we calculated adjusted hazard ratios for late BCR accounting for competing risks. Findings: Among 36,924 women with BC, 20,315 became 10-year disease-free survivors. Of these, 2,595 developed late BCR (IR=15·5 per 1,000 person-years, 95%CI=14·9-16·1; cumulative incidence=17%) from year 10 to 32 after primary diagnosis. The rate of late BCR was highest 10-12 years after diagnosis (IR=22·1 per 1,000 person-years, 95%CI=20·9-23·4). Tumor size >20mm, lymph node positive disease, grade I/II, and estrogen receptor positive (ER+) tumors were associated with increased cumulative incidences and hazards for late BCR. Interpretation: The risk of late BCR was highest in year 10-12 after primary diagnosis, but recurrences continued to occur up to 32 years after primary diagnosis. Particularly women with high lymph node burden, larger tumor size, lower grade, and an estrogen receptor positive tumor had increased risk of late recurrence. Funding Statement: The Danish Cancer Society (“Knaek Cancer” R147-A10100) and Aarhus University. Declaration of Interests: Dr. Ejlertsen reports: Nanostring Technologies, Inc. (grant: institutional), Novartis (grant:294 institutional), and Roche (grant: institutional), Astrazeneca (grant: institutional), Oncology Venture (grant: institutional), Pfizer (grant: institutional), Samsung (grant: institutional). Dr. Christiansen reports personal fees from Roche Denmark, non-financial support from Roche Denmark, outside the submitted work. Dr. Lash reports personal fees from Amgen, non-financial support from Amgen, outside the submitted work. Dr. Mellemkjaer reports an immediate family member has an employment at Novo Nordisk. An immediate family member owns stocks in Novo Nordisk. No other potential conflicts of interest were reported. Ethics Approval Statement: This study was approved by the Danish Breast Cancer Group and the Danish Data Protection Agency (Aarhus University, J. no. 2016-051-00001, record number 552) and adheres to the General Data Protection Regulations. The study is based on routinely collected registry data and according to Danish regulations does therefore not require separate ethical approval.

The University of North Carolina Heart-Lung Transplant Experience: Historical Perspective and Notes on Surveillance for Very Long-Term Survivors

Background: The University of North Carolina (UNC) pioneered heart-lung transplant (HLT) in the state of North Carolina in 1991. Specific guidelines for surveillance of very long-term survivors of HLT are non-existent. We report historical context for the UNC 30-year experience with HLT, complexity of subsequent medical care, and a standardized approach to follow-up. Methods: The medical and UNOS records for all patients who underwent HLT at UNC were reviewed. Demographics, perioperative details, and post-transplant medication regimens were abstracted. Early (30 day) and late (>30 days post HLT) morbidity was described, and Kaplan-Meier curves estimated long-term survival. Results: Overall, 15 patients (67% male, 73% adults) underwent HLT, and 80% had congenital heart disease. Five-, twenty-, and twenty-five-year survival was 40% (n=6), 27% (n=4), and 20% (n=3), respectively. All 15-year survivors (n=5) experienced late complications (infections-100%; chronic kidney disease-60%; malignancies-40%; and pulmonary allograft rejection-60%). None had cardiac graft rejection. Dedicated transplant cardiologists and pulmonologists directed long-term care, and survivors were followed every 6-12 months with non-invasive cardiopulmonary testing. Invasive testing with cardiac catheterization and/or bronchoscopy was performed every 2-3 years. Limitations: Limitations of the study include small sample size typical of a single-center study. However, this historicallysignificant series represents the entire HLT experience at UNC. Conclusion: UNC pioneered HLT in the state of North Carolina in 1991. HLT remains a rarely-performed, but viable option for end-staged cardiopulmonary failure as evidenced by favorable long-term survival. Late complications are common and warrant close surveillance and ongoing coordinated care by a specialized multi-disciplinary team.

Impact of Preoperative Serum Tumor Markers in Patients with Lung Squamous Cell Carcinoma

Background: Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefulness of serum tumor markers for lung squamous cell carcinoma (SQ). We aimed to examine the significance of serum tumor markers for lung SQ. Methods: Eighty-five lung SQ patients who underwent surgery and followed more than 5-year were included. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors, including tumor markers, were compared. We also compared the clinicopathologic factors between central type and peripheral type SQ. Results: The majority of patients were male gender and current/ former smokers. Age, pN status, cytokeratin-19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and comorbid interstitial pneumonia (IP) were associated with the ratio of 5-year survivors significantly. When patients were compared based on tumor location, high p-stage and CYFRA 21-1 were related to central type SQ. Conclusion: Both SCC and CYFRA 21-1 appeared to be useful prognostic markers for patients with lung SQ. Furthermore, CYFRA 21-1 was related to central type SQ.

Early sST2 Liberation after Implantation of a Left Ventricular Assist Device in Patients with Advanced Heart Failure.

Background The use of left ventricular assist device (LVAD) has increased considerably over the past decade; however, there is limited literature to assist in patient selection and monitoring. The frequency of adverse events remains high. We examined the early expression of circulating soluble ST2 (sST2), a biomarker with immunosuppressive and profibrotic activity, and assessed the risk of death at 1 year in patients receiving LVAD implant. Methods We prospectively enrolled 20 heart failure patients and measured sST2, IL-33, and IL-6 serum concentrations over three weeks after LVAD implantation. We compared the kinetics of IL-6, sST2, and IL-33 release in survivors with those of nonsurvivors using mixed model two-way analysis of variance for repeated measures. We also collected data on hemodynamic parameters (i.e., cardiac output) and frequency of infections during the hospital stay. Results LVAD therapy led to an immediate and significant improvement of the hemodynamic parameters in 1-year survivors and nonsurvivors alike. The 1-year survival rate was 65%. IL-6 concentrations showed a significant (p = 0.03) peak at admission to the intensive care unit following LVAD implantation, whereas sST2 levels were massively increased (p < 0.0003) on day 1. While 1-year survivors had persistently lower sST2 values compared to nonsurvivors during the first 3 weeks after LVAD implantation (p = 0.012), no differences were observed in the temporal pattern of IL-6 or IL-33. The odds of detecting Candida species in the bronchoalveolar lavage fluid were 14 times higher in nonsurvivors than in survivors (OR 13.7, CI 1.4-127, p = 0.02). Conclusion In patients implanted with LVAD, circulating sST2 levels and frequency of Candida colonisation were associated with higher mortality. Awareness of this early immune response can guide physicians in risk-benefit analysis.

Risk of Lymphoproliferative Disorders After Bone Marrow Transplantation: A Multi-Institutional Study

We evaluated 18,014 patients who underwent allogeneic bone marrow transplantation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders (PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years. Incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among >/=1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P <.0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P =.02) and with conditioning regimens that included radiation (RR = 2.9, P =.02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P =.009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P =.01). Rates of PTLD among patients with 2 or >/=3 major risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD.

Twenty-year survival following orthotopic heart transplantation in the United States.

This study evaluated 20-year survival after adult orthotopic heart transplantation (OHT). The United Network of Organ Sharing Registry database was queried to study adult OHT recipients between 1987 and 1998 with over 20-year posttransplant follow-up. The primary and secondary outcomes were 20-year survival and cause of death after OHT, respectively. Multivariable logistic regression was used to identify significant independent predictors of long-term survival, and long-term survival was compared among cohorts stratified by number of predictors using Kaplan Meier survival analysis. 20,658 patients undergoing OHT were included, with a median follow-up of 9.0 (IQR, 3.2-15.4) years. Kaplan-Meier estimates of 10-, 15-, and 20-year survival were 50.2%, 30.1%, and 17.2%, respectively. Median survival was 10.1 (IQR, 3.9-16.9) years. Increasing recipient age (>65 years), increasing donor age (>40 years), increasing recipient body mass index (>30), black race, ischemic cardiomyopathy, and longer cold ischemic time (>4 h) were adversely associated with a 20-year survival. Of these 6 negative predictors, presence of 0 risk factors had the greatest 10-year (59.7%) and 20-year survival (26.2%), with decreasing survival with additional negative predictors. The most common cause of death in 20-year survivors was renal, liver, and/or multisystem organ failure whereas graft failure more greatly impacted earlier mortality. This study identifies six negative preoperative predictors of 20-year survival with 20-year survival rates exceeding 25% in the absence of these factors. These data highlight the potential for very long-term survival after OHT in patients with end-stage heart failure and may be useful for patient selection and prognostication.

LINC-07. PREVALENCE AND SPECTRUM OF EARLY ENDOCRINE DISORDERS IN SURVIVORS OF PEDIATRIC EMBRYONAL BRAIN TUMORS (PEBT): EXPERIENCE FROM INDIA

BACKGROUNDSurvivors of pediatric brain tumors are at high risk of developing endocrine disorders, potentially impacting growth,development and quality of life.METHODSetrospective audit of 2-year survivors of PEBT(3-18years at diagnosis)viz. medulloblastoma(MB),Central nervous system Primitive neuro-ectodermal tumors(CNS-PNET) and atypical teratoid/rhabdoid tumor(ATRT) treated January 2006-December 2017 at Tata Memorial Centre,Mumbai, with surgery, cranio-spinal irradiation(CSI; 35Gy in high-risk MB,CNS-PNET,ATRT and 23.4Gy in average-risk MB with tumor boost 19.8Gy)and six cycles of adjuvant chemotherapy(cyclophosphamide,cisplatin and vincristine).Patients were followed up by a paediatric endocrinology team specialized in management of PEBT.RESULTSOf 249 PEBT treated during this period,88 are alive in remission >2 years (69-MB, 15-CNS PNET,4-ATRT),median age at diagnosis 6 years. At a median follow-up of 5.6 years (range 3- 12.5years),63 patients(72%) had at least one endocrine disorder,26(29.%)≥2 hormonal deficiencies. The most common endocrine disorders were central hypothyroidism(57%),growth hormone deficiency(40%), central hypogonadism(5%)and central hypoadrenalism (3.5%).The median time to develop hypothyroidism was 2.8 years(range 5months to 8.5 years) from CSI. Growth hormone replacement therapy began after a median period of 4.2 years(range-1.5 to 11.5years) from CSI. Higher dose of CSI was associated with development of endocrine disorder (odds ratio [OR] 2.71; 95% CI, 1.03 to 7.04,p-0.04).CONCLUSIONSThe high incidence of endocrine deficits in survivors of PEBT necessitates early and lifelong monitoring. Early and appropriate management is crucial to achieve full growth potential.

EPID-30. PREDICTORS ASSOCIATED WITH LONG-TERM SURVIVORSHIP FOR PATIENTS WITH GLIOBLASTOMA USING THE NATIONAL CANCER DATABASE (NCDB)

Abstract OBJECTIVES To investigate the long-term survival rates and the related predictors in patients with glioblastoma (GBM) using NCDB. METHODS A total of 51570 GBM patients were derived from the NCDB from 2004 to 2011. Three long-term survival measures were defined as patients who lived for at least 3-year, 5-year, or 10-year after diagnosis, respectively. Multivariable binary logistic regressions were performed to identify predictors in relation to 3-year, 5-year, and 10-year survival rates. The relative importance of each survival predictors was calculated, and random forest method was performed to validate the variable importance and decision tree as well. RESULTS A total of 4782 (9.3%), 1481 (3.9%), and 51 (0.9%) GBM patients survived at least 3-year, 5-year, and 10-years, respectively. Significant predictors related to both 3-year and 5-year survival rates from multivariable logistic regression included tumor resection, recent year of diagnosis, age &amp;lt; 65 years, private insurance, adjuvant therapy, non-whites, female, treatment at facility located in South regions or academic facilities, higher income, and non-comorbidity. Moreover, patients who traveled &amp;gt;50 miles for treatment and received care transition were significantly more likely to survival at least 3 years. However, only five predictors were associated with 10-year survivorship: residence-hospital distance &amp;gt;20 miles, non-whites, age &amp;lt; 65 years, resection, and higher income. Based on the calculations of relative importance and random forest method, the most important five factors to predict long-term survival were age, tumor resection, year of diagnosis, comorbidity, and adjuvant therapy (3-year survival); age, tumor resection, comorbidity, gender, and insurance (5-year survival); and age, race, residence-hospital distance, income, and comorbidity (10-year survival), respectively. CONCLUSIONS This study identifies non-molecular factors predicting long-term survivorship among GBM patients using NCDB dataset. Our findings suggested that 3-year and 5-year survivors share similar determinants, while 10-year survivors could be more different in socio-demographics and clinical features.