Citations

INTRODUCTION: The discontinuous BALAD and continuous BALAD-2 scores derived from bilirubin, albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) are effective in predicting HCC patient mortality, but have not been validated in North America. We validated the BALAD and BALAD-2 scores in North America. METHODS: Data from 148 HCC patients seen from 2000–2015 with results for all five biomarkers at diagnosis were abstracted. Hazard ratios (HR) and C-statistics were calculated. RESULTS: 75 of the 148 patients died during a median follow-up of 33 months (0.3-145 months),. The 1-year and 3-year survival rates were 70.8% and 47.6%, respectively. 114 (77%) patients had cirrhosis with a median MELD of 9.5 (range 6.4-29.5). HCC etiologies were HCV (34%), NASH (34%), alcohol (14%), and HBV (10%). Primary treatments were liver transplant, 21 (14%), surgical resection, 32 (22%), local ablation, 10 (7%), transarterial chemoembolization or radioembolization, 47 (32%), chemotherapy, 11 (7%), best supportive care, 9 (6%), and unknown treatment, 18 (12%). MELD, tumor size (cm), ≥2 tumors, tumor number, and neutrophil-lymphocyte ratio >4 significantly increased mortality with HR (95%CI) of 1.12 (1.06–1.18) per unit increase in MELD, 1.06 (1.0004–1.12) per cm increase in size, 1.21 (1.03–1.43) per number of tumor, and 1.93 (1.16–3.24). For the BALAD score analysis, 12, 49, 40, 31, 16 and 0 patients had BALAD scores of 0–5 respectively. The HR (95%CI) for death were 1.24 (0.42–3.67), 1.79 (0.61–5.26), 2.83 (0.95–8.38), and 7.19 (2.26–22.91) for BALAD scores 1, 2, 3, and 4 vs. BALAD 0. For the BALAD-2 analysis, 58, 35, 33, and 22 patients were BALAD-2 classes 1, 2, 3, and 4. The HR (95%CI) for death were 1.25 (0.65–2.40), 1.75 (0.94–3.23), and 6.20 (3.29–11.68) for BALAD-2 classes 2, 3, and 4 vs. BALAD-2 class 1. A multivariate model incorporating maximal tumor diameter, tumor number, neutrophil-lymphocyte ratio and BALAD had HR of 1.43 (1.14–1.81) per increase of 1 BALAD score. A similar multivariate model with BALAD-2 had HR of 1.50 (1.18–1.90) per increase of 1 BALAD-2 class. BALAD, BALAD-2 and BCLC had similar C-statistics of 0.69, 0.68, and 0.67. CONCLUSION: The BALAD score and BALAD-2 class at HCC diagnosis can predict survival of HCC patients in North America. AFP, AFP-L3, and DCP in the BALAD models incorporate HCC tumor biology and make the BALAD model distinguish from other previous predictive models.

OBJECTIVES: Cardiovascular (CV) disease is the top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Female sex is protective against CV disease. We aimed to determine whether female sex remains a protective factor against CV disease (myocardial infarction, angina, and stroke) in NAFLD. METHODS: We identified all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 and selected an age- and sex-matched (1:4) referent cohort from the general population. NAFLD was ascertained using a code-based algorithm with high validity tested by medical record review. The impact of female sex on incident CV events was examined using Cox proportional hazards regression analysis stratified by standard clinical risk factors. RESULTS: A total of 3,869 NAFLD and 15,209 age- and sex-matched referent subjects were identified. After a median follow-up time of 7 (range 1–20) years, 3,851 CV events were recorded. Female sex was protective for ischemic CV events in the general population (hazard ratio = 0.71, 95% confidence interval 0.62–0.80, P < 0.001), but the impact was significantly diminished among those with NAFLD (hazard ratio = 0.90, 95% confidence interval 0.74–1.08, P = 0.25), even after stratification by time-dependent CV risk factors and control for diagnostic testing (liver enzymes and ultrasound) during routine medical evaluations, as a surrogate of access to care. Among those with NAFLD, excess events were higher in women than in men: CV disease (18% vs 9%) and mortality (9% vs 6%). DISCUSSION: Women with NAFLD lose the CV protection conferred by the female sex, and their risk is underestimated by current estimating methods in clinical practice.

Objectives Treatment burden is the workload of healthcare for people with long-term conditions (LTC) and its impact on well-being. A method of measurement is required to identify those experiencing high burden and to measure intervention efficacy. Our aim was to identify, examine and appraise validated patient-reported measures (PRMs) of treatment burden in stroke. Here, stroke serves as an exemplar LTC of older adults. Design A systematic review of published studies that describe the development and validation of PRMs measuring treatment burden in stroke survivors. Data sources We searched MEDLINE, Embase, CINAHL and PsycINFO electronic databases. Eligibility criteria Studies published between January 2000 and 12 April 2019 inclusive, in English language. No restrictions were set based on clinical setting or geographical location. Data extraction and synthesis Screening, data extraction and quality appraisal were conducted by two independent reviewers. Content of the PRMs was compared with a published taxonomy of treatment burden. Quality appraisal was conducted using International Society for Quality of Life Research standards. Results From 3993 articles, 6 relevant PRMs were identified: 3 were stroke specific: The Satisfaction with Stroke Care questionnaire; The Stroke Patient-Reported Outcome Measure and The Barriers to Physical Activity after Stroke scale. Three were generic but validated in stroke: The WHO Quality of Life-100; The Patient’s Questionnaire on Participation in Discharge Planning and The Chao Perception of Continuity scale. None comprehensively measured treatment burden. Examples of omitted burdens included developing coping strategies, managing finances and returning to driving. The most notable issue regarding quality appraisal was that three PRMs lacked any underpinning qualitative research relevant to the sample. Conclusion There is a need to develop a comprehensive PRM of treatment burden for use in stroke, with potential for use in other older populations.

See Gordon and Tijms (doi:10.1093/brain/awz278) for a scientific commentary on this article. Jack et al. examine relationships between the bivariate distribution of β-amyloid and tau on PET and established neurocognitive clinical syndromes. Amyloidosis appears to be required for high levels of 3R/4R tau deposition. Whereas abnormal amyloid PET is compatible with normal cognition, highly abnormal tau PET is not.

Abstract BACKGROUND: It is well known that for patients with solitary metastatic disease in the brain, aggressive surgical treatment can prolong survival. However, there is a paucity of literature focusing on simultaneous resection of multiple metastatic brain tumors. METHODS: We analyzed 13 patients and 26 tumors between 2005–2019 who had simultaneous resection of at least 2 metastatic brain tumors via either one or two craniotomies. We independently analyzed those patients with simultaneous resection of metastatic disease in both the supra- and infratentorial compartments. RESULTS: Overall, 26 tumors were resected in a simultaneous fashion. There were 7 females (53.8%) and 6 males (46.2%) total. 5/13 (38.5%) patients had previously known brain metastases in which all 5 had previous adjuvant radiation. All 13 patients had 2 metastatic lesions resected during one operation. Gross total resection rate reached 88.5% with a median post-operative stay of 3 days. Complications presented in only 3 out of 13 cases (grade 2 and 3 according to CTCAE). Primary sites of metastatic disease were lung, breast, skin and renal. 12/13 (92.3%) had two distinct craniotomies and 23/26 (88.5%) tumors had gross total resection of both lesions. There were 11 frontal (42.3%), 7 parietal (26.9%), 2 temporal (7.7%), 1 occipital (3.8%) and 5 cerebellar (19.2%) tumors. There were three patients with both supra- and intratentorial tumors with simultaneous resection. All three patients had two craniotomies and two separate incisions. 1 of the 3 had pre-operative SRS. Overall, average local progression since surgery to at least one resected tumor bed was 88.3 days. CONCLUSIONS: Our results suggest that patients with multiple metastatic brain lesions have comparable outcomes and similar rates of surgical risk to those with solitary brain lesions. In patients with simultaneous supra- and infratentorial brain metastatic disease and indications for decompression, safe resection is feasible.

Abstract PURPOSE: Preoperative stereotactic radiosurgery (SRS) for symptomatic brain metastases has arisen as a therapeutic option for patients with brain lesions, potentially reducing radionecrosis risk, leptomeningeal disease risk, as well as delays in systemic therapy after craniotomy. The purpose of our work is to analyze the current evidence regarding 1-year local control (LC) and RN rates in the preoperative and postoperative settings. METHODS AND MATERIALS: Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (&gt;4 cm3 or &gt;2 cm in diameter) solely treated with preoperative or postoperative SRS and 1-year LC and/or rates of RN reported. Radiosurgery was stratified by timing: preoperatively or postoperatively. Random effects meta-analyses using timing of SRS relative to surgery as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size on the summary estimate, where the null hypothesis was rejected for p &lt; 0.05. RESULTS: Fifteen studies were included (of 314 screened), published between 2012 and 2018 with 854 brain metastases. Preoperative SRS was delivered in 229 lesions. The 1-year LC random effects estimate was 79.1% (95% confidence interval [CI]: 55.9–95.0%; I 2 = 80%) for preoperative SRS and 80.5% (95% CI: 66.3–91.5%; I 2 = 93%) for postoperative SRS (p=0.9). Radionecrosis incidence random effects estimate was 2.1% (95% CI: 0.1–8.6%; I 2 = 36%) for preoperative SRS and 6.3% (95% CI: 1.1–15.4%; I 2 = 90%) for postoperative SRS (p=0.52). CONCLUSIONS: Rates of 1-year LC and RN incidence are similar after preoperative SRS as compared to postoperative SRS for large brain metastases. Results from ongoing prospective clinical trials studying preoperative SRS are important to further investigate these two techniques.

Abstract Objectives: Biliary tract cancers (BTCs) comprise the second most common type of hepatobiliary cancer. Given the increase in global BTC incidence, with associated morbidity and mortality, together with the limited therapeutic options, there is increasing interest in strategies for disease prevention. We performed a population-based cohort study to determine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. Methods: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. Results: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00,p=0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94,p=0.03) and men (HR 0.47,0.28-0.80,p=0.01). Low dose aspirin (HR 0.76,0.60-0.97,p=0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93,p=0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. Conclusion: We performed the largest population-based cohort study evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype-and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. If randomized controlled clinical trials validate our findings and provide favorable evidence of the efficacy and safety of these drugs in the prevention of BTCs, our results could potentially be practice-changing, leading to improvements in the outcomes in this population. Citation Format: Lorena Marcano-Bonilla, Cathy D. Schleck, W. Scott Harmsen, Omid Sadr-Azodi, Mitesh J. Borad, Tushar Patel, Gloria M. Petersen, Terry M. Therneau, Lewis R. Roberts, Nele Brusselaers. Associations of aspirin, non-aspirin NSAIDs, statins, and metformin with risk of biliary tract cancer: A Swedish population-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5049.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.