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The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.
Copyright © 2018 by the National Comprehensive Cancer Network.

Cardiovascular disease (CVD), which includes cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction, is a major concern for long-term survivors of childhood cancer. There is clear evidence of increased risk of CVD largely attributable to treatment exposures at a young age, most notably anthracycline chemotherapy and chest-directed radiation therapy, and compounded by traditional cardiovascular risk factors accrued during decades after treatment exposure. Preclinical studies are limited; thus, it is a high priority to understand the pathophysiology of CVD as a result of anticancer treatments, taking into consideration the growing and developing heart. Recently developed personalized risk prediction models can provide decision support before initiation of anticancer therapy or facilitate implementation of screening strategies in at-risk survivors of cancer. Although consensus-based screening guidelines exist for the application of blood and imaging biomarkers of CVD, the most appropriate timing and frequency of these measures in survivors of childhood cancer are not yet fully elucidated. Longitudinal studies are needed to characterize the prognostic importance of subclinical markers of cardiovascular injury on long-term CVD risk. A number of prevention trials across the survivorship spectrum are under way, which include primary prevention (before or during cancer treatment), secondary prevention (after completion of treatment), and integrated approaches to manage modifiable cardiovascular risk factors. Ongoing multidisciplinary collaborations between the oncology, cardiology, primary care, and other subspecialty communities are essential to reduce therapeutic exposures and improve surveillance, prevention, and treatment of CVD in this high-risk population.

BACKGROUND - Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment.
METHODS - In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders.
FINDINGS - Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01).
INTERPRETATION - Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation.
FUNDING - National Institutes of Health and the Department of Veterans Affairs.
Copyright © 2018 Elsevier Ltd. All rights reserved.

OBJECTIVES - Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness.
DESIGN - Secondary analysis of a prospective cohort study.
SETTING - Medical/surgical ICU of a U.S. tertiary care medical center.
PATIENTS - Three hundred seventeen participants with respiratory failure and/or shock.
INTERVENTIONS - None.
MEASUREMENTS AND MAIN RESULTS - Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed.
CONCLUSIONS - Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes.

Many cancer survivors experience menopausal symptoms, including female survivors taking aromatase inhibitors or with a history of oophorectomy or chemotherapy, and male survivors who received or are receiving androgen-ablative therapies. Sexual dysfunction is also common in cancer survivors. Sexual dysfunction and menopause-related symptoms can increase distress and have a significant negative impact on quality of life. This portion of the NCCN Guidelines for Survivorship provide recommendations for screening, evaluation, and treatment of sexual dysfunction and menopausal symptoms to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period.
Copyright © 2017 by the National Comprehensive Cancer Network.

Our purpose was to characterize the clinical influences, genetic risk factors, and gene mechanisms contributing to persistent cisplatin-induced peripheral neuropathy (CisIPN) in testicular cancer survivors (TCSs). TCS given cisplatin-based therapy completed the validated EORTC QLQ-CIPN20 questionnaire. An ordinal CisIPN phenotype was derived, and associations with age, smoking, excess drinking, hypertension, body mass index, diabetes, hypercholesterolemia, cumulative cisplatin dose, and self-reported health were examined for 680 TCS. Genotyping was performed on the Illumina HumanOmniExpressExome chip. Following quality control and imputation, 5.1 million SNPs in 680 genetically European TCS formed the input set. GWAS and PrediXcan were used to identify genetic variation and genetically determined gene expression traits, respectively, contributing to CisIPN. We evaluated two independent datasets for replication: Vanderbilt's electronic health database (BioVU) and the CALGB 90401 trial. Eight sensory items formed a subscale with good internal consistency (Cronbach α = 0.88). Variables significantly associated with CisIPN included age at diagnosis (OR per year, 1.06; = 2 × 10), smoking (OR, 1.54; = 0.004), excess drinking (OR, 1.83; = 0.007), and hypertension (OR, 1.61; = 0.03). CisIPN was correlated with lower self-reported health (OR, 0.56; = 2.6 × 10) and weight gain adjusted for years since treatment (OR per Δkg/m, 1.05; = 0.004). PrediXcan identified lower expressions of and and higher expression as associated with CisIPN ( value for each < 5 × 10) with replication of meeting significance criteria (Fisher combined = 0.0089). CisIPN is associated with age, modifiable risk factors, and genetically determined expression level of Further study of implicated genes could elucidate the pathophysiologic underpinnings of CisIPN. .
©2017 American Association for Cancer Research.

To assess the effect of chemotherapy on mitochondrial genome mutations in cancer survivors and their offspring, a study sequenced the full mitochondrial genome and determined the mitochondrial DNA heteroplasmic (mtDNA) mutation rate. To build a model for counts of heteroplasmic mutations in mothers and their offspring, bivariate Poisson regression was used to examine the relationship between mutation count and clinical information while accounting for the paired correlation. However, if the sequencing depth is not adequate, a limited fraction of the mtDNA will be available for variant calling. The classical bivariate Poisson regression model treats the offset term as equal within pairs; thus, it cannot be applied directly. In this research, we propose an extended bivariate Poisson regression model that has a more general offset term to adjust the length of the accessible genome for each observation. We evaluate the performance of the proposed method with comprehensive simulations, and the results show that the regression model provides unbiased parameter estimations. The use of the model is also demonstrated using the paired mtDNA dataset.

INTRODUCTION - Survivors of thrombotic thrombocytopenic purpura (TTP) have high rates of chronic morbidities including neurocognitive complications and depression. There is limited information regarding the psychological consequences of TTP. We conducted this cross sectional study to estimate the prevalence of symptoms of PTSD and depression in survivors of TTP.
METHODS - An online survey tool comprising demographic and clinical information and two validated self-administered questionnaires, the PTSD checklist for DSM-5 (PCL-5) and Beck Depression Inventory-II (BDI-II), was distributed to individuals with TTP. Multivariable regression was used to identify clinical and demographic associations of depression and PTSD.
RESULTS - A total of 236 individuals completed either the BDI II or PCL-5 and were included in the analysis. Median age was 44years and 87.3% were female. Median time from diagnosis was 80months. BDI-II scores >13 indicating at least mild depressive symptoms were present in 80.8% individuals (15.8%, 28.2%, and 36.8% with mild, moderate and severe symptoms, respectively) and 35.1% had a positive screen for PTSD (PCL-5 score≥38). A previous diagnosis of depression [OR 3.65 (95% CI 1.26-10.57); p=0.017] and unemployment attributed to TTP [OR 5.86 (95% CI 1.26-27.09); p=0.024] were associated with depression. Younger age (p=0.017), a pre-existing anxiety disorder [OR 3.57 (95% CI 1.76-7.25), p<0.001], and unemployment attributable to TTP [OR 6.42 (95% CI 2.75-415.00), p<0.001] were associated with PTSD.
CONCLUSION - We report a high prevalence of PTSD and depression in TTP survivors. These results are concerning and indicate a need for further investigation to better define this association and its consequences.
Copyright © 2017 Elsevier Ltd. All rights reserved.

Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.