Summary Background The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. Methods We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. Findings 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to Interpretation Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder. Funding The National Breast Cancer Foundation, Australia.

Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis

In the United States, approximately 14 million people have had cancer and more than 1.6 million new cases are diagnosed each year. However, more than a decade after the Institute of Medicine (IOM) first studied the quality of cancer care, the barriers to achieving excellent care for all cancer patients remain daunting. Care often is not patient-centered, many patients do not receive palliative care to manage their symptoms and side effects from treatment, and decisions about care often are not based on the latest scientific evidence. The cost of cancer care also is rising faster than many sectors of medicine--having increased to $125 billion in 2010 from $72 billion in 2004--and is projected to reach $173 billion by 2020. Rising costs are making cancer care less affordable for patients and their families and are creating disparities in patients' access to high-quality cancer care. There also are growing shortages of health professionals skilled in providing cancer care, and the number of adults age 65 and older--the group most susceptible to cancer--is expected to double by 2030, contributing to a 45 percent increase in the number of people developing cancer. The current care delivery system is poorly prepared to address the care needs of this population, which are complex due to altered physiology, functional and cognitive impairment, multiple coexisting diseases, increased side effects from treatment, and greater need for social support. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis presents a conceptual framework for improving the quality of cancer care. This study proposes improvements to six interconnected components of care: (1) engaged patients; (2) an adequately staffed, trained, and coordinated workforce; (3) evidence-based care; (4) learning health care information technology (IT); (5) translation of evidence into clinical practice, quality measurement and performance improvement; and (6) accessible and affordable care. This report recommends changes across the board in these areas to improve the quality of care. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis provides information for cancer care teams, patients and their families, researchers, quality metrics developers, and payers, as well as HHS, other federal agencies, and industry to reevaluate their current roles and responsibilities in cancer care and work together to develop a higher quality care delivery system. By working toward this shared goal, the cancer care community can improve the quality of life and outcomes for people facing a cancer diagnosis.

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Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis

A detailed understanding of the mechanisms by which tumors acquire resistance to targeted anticancer agents should speed the development of treatment strategies with lasting clinical efficacy. RAF inhibition in BRAF-mutant melanoma exemplifies the promise and challenge of many targeted drugs; although response rates are high, resistance invariably develops. Here, we articulate overarching principles of resistance to kinase inhibitors, as well as a translational approach to characterize resistance in the clinical setting through tumor mutation profiling. As a proof of principle, we performed targeted, massively parallel sequencing of 138 cancer genes in a tumor obtained from a patient with melanoma who developed resistance to PLX4032 after an initial dramatic response. The resulting profile identified an activating mutation at codon 121 in the downstream kinase MEK1 that was absent in the corresponding pretreatment tumor. The MEK1 C121S mutation was shown to increase kinase activity and confer robust resistance to both RAF and MEK inhibition in vitro. Thus, MEK1 C121S or functionally similar mutations are predicted to confer resistance to combined MEK/RAF inhibition. These results provide an instructive framework for assessing mechanisms of acquired resistance to kinase inhibition and illustrate the use of emerging technologies in a manner that may accelerate personalized cancer medicine. J Clin Oncol 29:3085-3096. © 2011 by American Society of Clinical Oncology

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Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.

The goal of this paper is to update a more extensive review and guidelines paper published in 2012 [1] . Gen-erally, any pertinent update pertaining to the diagnosis and staging of individual prima ...

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016;66:290-308. © 2016 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21340

Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities

Importance The incidence and prevalence of neuroendocrine tumors (NETs) are thought to be rising, but updated epidemiologic data are lacking. Objective To explore the evolving epidemiology and investigate the effect of therapeutic advances on survival of patients with NETs. Design, Setting, and Participants A retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results (SEER) program was conducted to evaluate 64 971 patients with NETs from 1973 to 2012. Associated population data were used to determine annual age-adjusted incidence, limited-duration prevalence, and 5-year overall survival (OS) rates. Trends in survival from 2000 to 2012 were evaluated for the entire cohort as well as specific subgroups, including distant-stage gastrointestinal NETs and pancreatic NETs. Analyses were conducted between December 2015, and February 2017. Main Outcomes and Measures Neuroendocrine tumor incidence, prevalence, and OS rates. Results Of the 64 971 cases of NETs, 34 233 (52.7%) were women. The age-adjusted incidence rate increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000). This increase occurred across all sites, stages, and grades. In the SEER 18 registry grouping (2000-2012), the highest incidence rates were 1.49 per 100 000 in the lung, 3.56 per 100 000 in gastroenteropancreatic sites, and 0.84 per 100 000 in NETs with an unknown primary site. The estimated 20-year limited-duration prevalence of NETs in the United States on January 1, 2014, was 171 321. On multivariable analyses, the median 5-year OS rate varied significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis. The OS rate for all NETs improved from the 2000-2004 period to the 2009-2012 period (hazard ratio [HR], 0.79; 95% CI, 0.73-0.85). Even larger increases in OS between these periods were noted in distant-stage gastrointestinal NETs (HR, 0.71; 95% CI, 0.62-0.81) and distant-stage pancreatic NETs (HR, 0.56; 95% CI, 0.44-0.70). Conclusions and Relevance The incidence and prevalence of NETs are steadily rising, possibly owing to detection of early-stage disease and stage migration. Survival for all NETs has improved over time, especially for distant-stage gastrointestinal NETs and pancreatic NETs in particular, reflecting improvement in therapies. These data will help to prioritize future research directions.

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Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States.

Purpose This study estimated the economic burden of breast cancer–related lymphedema (BCRL) among working-age women, the incidence of lymphedema, and associated risk factors. Methods We used claims data to study an incident cohort of breast cancer patients for the 2 years after the initiation of cancer treatment. A logistic regression model was used to ascertain factors associated with lymphedema. We compared the medical costs and rate of infections likely associated with lymphedema between a woman with BCRL and a matched control. We performed nonparametric bootstrapping to compare the unadjusted cost differences and estimated the adjusted cost differences in regression analysis. Results Approximately 10% of the 1,877 patients had claims indicating treatment of lymphedema. Predictors included treatment with full axillary node dissection (odds ratio [OR] = 6.3, P < .001) and chemotherapy (OR = 1.6, P = .01). A geographic variation was observed; women who resided in the West were more likely to have lymphed...

Incidence, Treatment Costs, and Complications of Lymphedema After Breast Cancer Among Women of Working Age: A 2-Year Follow-Up Study

Summary Background Neuroendocrine tumours (NETs) can secrete bioactive amines into the bloodstream, causing carcinoid syndrome, with symptoms including flushing and diarrhoea. However, carcinoid syndrome frequency in the NET population has never been rigorously assessed, nor has its relationship to presenting clinicopathological characteristics. This analysis assessed the proportion of patients with NETs and carcinoid syndrome in the USA and associated clinical factors. Methods We identified patients (≥65 years of age) from the Surveillance, Epidemiology, and End Results-Medicare database, excluding those with pancreatic tumours or small-cell or large-cell lung cancer, as well as those without complete data. We assessed the incidence of patients with at least two insurance claims of flushing, diarrhoea, or carcinoid syndrome during the 3 months before and after NET diagnosis. We compared demographic and clinical characteristics between patients with and without carcinoid syndrome using χ 2 tests. We used the Cochran-Armitage trend test to identify trends in carcinoid syndrome incidence and Cox regression to assess the relationship between carcinoid syndrome and survival. Findings Between April 1, 2000, and Dec 31, 2011, 9512 eligible patients were diagnosed with NETs, of whom 1786 (19%) had carcinoid syndrome. The number of patients with NETs and carcinoid syndrome increased from 50 (11%) of 465 patients in 2000 to 160 (19%) of 854 in 2011 (p Interpretation This population-based analysis reveals that carcinoid syndrome is significantly associated with tumour grade, stage, and primary tumour site, and leads to shorter survival compared with those patients without carcinoid syndrome. An improved understanding of the heterogeneity of presenting symptoms among patients with NETs might permit more tailored assessment and management than at present and enable future research into the effect of carcinoid syndrome control on patient survival. Funding Ipsen.

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Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study

Context Brachytherapy is a radiation treatment that uses an implanted radioactive source. In recent years, use of breast brachytherapy after lumpectomy for early breast cancer has increased substantially despite a lack of randomized trial data comparing its effectiveness with standard whole-breast irradiation (WBI). Because results of long-term randomized trials will not be reported for years, detailed analysis of clinical outcomes in a nonrandomized setting is warranted. Objective To compare the likelihood of breast preservation, complications, and survival for brachytherapy vs WBI among a nationwide cohort of older women with breast cancer with fee-for-service Medicare. Design Retrospective population-based cohort study of 92 735 women aged 67 years or older with incident invasive breast cancer, diagnosed between 2003 and 2007 and followed up through 2008. After lumpectomy 6952 patients were treated with brachytherapy vs 85 783 with WBI. Main Outcome Measures Cumulative incidence and adjusted risk of subsequent mastectomy (an indicator of failure to preserve the breast) and death were compared using the log-rank test and proportional hazards models. Odds of postoperative infectious and noninfectious complications within 1 year were compared using the χ 2 test and logistic models. Cumulative incidences of long-term complications were compared using the log-rank test. Results Five-year incidence of subsequent mastectomy was higher in women treated with brachytherapy (3.95%; 95% CI, 3.19%-4.88%) vs WBI (2.18%; 95% CI, 2.04%-2.33%; P  Conclusion In a cohort of older women with breast cancer, treatment with brachytherapy compared with WBI was associated worse with long-term breast preservation and increased complications but no difference in survival.

https://jamanetwork.com/journals/jama/articlepdf/1150095/joc120007_1827_1837.pdf

Association Between Treatment With Brachytherapy vs Whole-Breast Irradiation and Subsequent Mastectomy, Complications, and Survival Among Older Women With Invasive Breast Cancer

BACKGROUND.

Chemotherapy-induced nausea and vomiting (CINV) is among the most feared side effects of cancer treatment. Poorly controlled CINV may lead to additional office visits or emergency room admissions, thus increasing the overall costs of cancer care. The objective of the project was to estimate the societal costs of uncontrolled CINV among working-age cancer patients.



METHODS.

The 1997–2002 Health and Productivity Management database, a proprietary database linking medical claims to work loss information, was used. The study population consisted of employees or their spouses who were cancer patients treated with highly or moderately emetogenic chemotherapy regimens. Costs of uncontrolled CINV were estimated by comparing the direct medical costs and indirect costs between those with and without uncontrolled CINV; all costs were normalized as monthly costs and updated to 2006 US dollars. The Wilcoxon Mann-Whitney test was used to compare the costs differences in univariate analyses, followed by multivariate analyses.



RESULTS.

In all, 2018 patients were identified; 1771 (88%) received 5-HT3 receptor antagonists, and uncontrolled CINV was found in 563 (28%). The estimated monthly medical costs associated with uncontrolled CINV were approximately $1300 higher for cancer patients at working ages. Subgroup analysis concluded that indirect costs per patient per month were $433 higher for those in the uncontrolled CINV group.



CONCLUSIONS.

Despite a prevalent use of the 5-HT3 receptor antagonists, uncontrolled CINV remained a common and costly problem among cancer patients treated with highly or moderately emetogenic chemotherapy. Cancer 2007. © 2007 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.22823

Costs of uncontrolled chemotherapy-induced nausea and vomiting among working-age cancer patients receiving highly or moderately emetogenic chemotherapy.

Ying Xu

Papers

Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States.

Incidence, Treatment Costs, and Complications of Lymphedema After Breast Cancer Among Women of Working Age: A 2-Year Follow-Up Study

Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study

Association Between Treatment With Brachytherapy vs Whole-Breast Irradiation and Subsequent Mastectomy, Complications, and Survival Among Older Women With Invasive Breast Cancer

Costs of uncontrolled chemotherapy-induced nausea and vomiting among working-age cancer patients receiving highly or moderately emetogenic chemotherapy.