bluuebunny/crossref_metadata_2025 huggingface dataset:
Aclidinium bromide in fixed-dose combination with formoterol fumarate in the management of COPD: an update on the evidence base
Authors: D’Urzo Anthony D. , Singh Dave , Donohue James F. , Chapman Kenneth R.
Published: May 2019

Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 µg is a twice-daily long-acting muscarinic receptor antagonist and long-acting β2 agonist (LAMA/LABA) dual-bronchodilator maintenance therapy used to relieve symptoms and reduce future risk of exacerbations in adults with chronic obstructive pulmonary disease (COPD). To date, there have been several clinical studies and post hoc analyses of AB/FF, assessing treatment outcomes in patients with moderate-to-severe COPD. These studies have looked at a range of outcomes, including lung function parameters, patient-reported symptom scores, quality-of-life measures assessing impaired health and perceived well-being, and the frequency, duration, and severity of exacerbations. In light of the major 2017 revision to the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, and the subsequent updates, we present an update on the latest evidence supporting the efficacy and safety of AB/FF. This review discusses the clinical relevance of the improvements in lung function, symptoms, quality of life, and exacerbations in patients with COPD reported in the phase III and IV trials of AB/FF. Given the current concerns over unnecessary inhaled corticosteroid (ICS) use in COPD, we also touch briefly on the use of blood eosinophils as a biomarker for identifying those patients with COPD already using LAMA/LABA therapy for whom the addition of ICS might be of benefit.
New frontiers in the medical management of gastrointestinal stromal tumours
Authors: Mazzocca Alessandro , Napolitano Andrea , Silletta Marianna , Spalato Ceruso Mariella , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno
Published: May 2019

The tyrosine kinase inhibitor (TKI) imatinib has radically changed the natural history of KIT-driven gastrointestinal stromal tumours (GISTs). Approved second-line and third-line medical therapies are represented by the TKIs sunitinib and regorafenib, respectively. While imatinib remains the cardinal drug for patients with GISTs, novel therapies are being developed and clinically tested to overcome the mechanisms of resistance after treatments with the approved TKI, or to treat subsets of GISTs driven by rarer molecular events. Here, we review the therapy of GISTs, with a particular focus on the newest drugs in advanced phases of clinical testing that might soon change the current therapeutic algorithm.
Supporting Good Intentions With Good Evidence: How to Increase the Benefits of Diabetes Social Media
Authors: Reidy Claire , Klonoff David C. , Barnard-Kelly Katharine D.
Published: May 2019

Social media provides a platform for easily accessible, relevant health information and emotional and practical support at the touch of a button for millions of people with diabetes. Therein however lies a challenge. The accuracy and reliability of such information is often unknown and unverified, not all interactions are deemed supportive; practically or emotionally, and not all members of society have equitable access. Cyber bullying, requests for personal information and uninvited sharing are among the risks associated with social media, yet the use of online social media is increasing exponentially. Such reliance on web-based health information has given rise to concerns about patients’ ability to accurately assess the credibility of online sources as well as the potential detrimental effect on personal well-being and patient-provider relations. In addition, there are rising digital disparities for particular subpopulations. Further, these concerns apply to where and how health care professionals should engage or refer patients to in terms of platforms of online support. There is little doubt regarding the popularity of social media, both within and outside of the health arena but there are also concerns. This article outlines five key areas associated with social media use in people living with diabetes and presents potential considerations moving forward. We focus on (1) social media as a platform for information and support; (2) social media interactions that are not supportive; (3) lessons from the DOC; (4) concerns about accuracy, reliability, and accessibility of information; and (5) differing priorities of health care professionals and patients.
Differences in Stereoscopic Luster Evoked by Static and Dynamic Stimuli
Authors: Wendt Gunnar , Faul Franz
Published: May 2019

We compared the classic static stereoscopic luster phenomenon with a recently described dynamic variant (“counter modulation”) to investigate whether they are related to the same or different processes. In the experiments, we presented pairs of center-surround stimuli haploscopically and measured the effect of the contrast between center colors on perceived luster. The center colors were either static or temporally modulated. In addition, we examined five color conditions (one achromatic, two equiluminant, and two mixed conditions) and three background conditions that influence the channel-wise polarities of the contrast of the two centers to the common surround. The results for static and dynamic stimuli differed in several ways, suggesting that they depend on different mechanisms: Compared with the static version, in dynamic stimuli, luster was perceived at markedly lower contrasts, did not depend on the sign of the contrast polarities, and appeared more steady. However, both phenomena seem also similar in some respects: In both cases, equiluminant stimuli led to lustrous impressions that were considerably less strong than those evoked by stimuli containing luminance variation, and the strength of the perceived luster was generally boosted with reversed contrast polarities.
GraceKennedy Group: The new Chief Information Officer and IT Governance
Authors: Golding Paul , Facey-Shaw Lisa
Published: May 2019

Grace Kennedy Group was the fourth largest Jamaican company listed on the Jamaican Stock Exchange by market capitalization in 2016. The company operated in several market segments focusing mainly on foods and financial services industries. Geographically, GraceKennedy Group had a diversified revenue stream operating across the Caribbean, Central and North America, Europe and Africa. Diversification had led to a diverse set of Information Technology platforms to serve the needs of the various subsidiaries of GraceKennedy Group. With the emergence of new technological trends like big data, social and cloud computing, the Group’s Audit Committee in 2014 conducted a risk profile around the company’s IT governance structure. The Committee recommended a change in the decentralized model of IT governance and the hiring of a Chief Information Officer to inter alia, strategically using IT to create value and to coordinate system security. The Chief Information Officer position was externally advertised; however, after several interviews, the Chief Executive Officer decided to offer the position to Robert Sutherland the then general manager of one of its subsidiaries. Sutherland was a former chairman of the Business Technology (BizTech) Council which was established in 2006 to oversee the delivery of IT services within the group and to provide guidance to the business leadership on enterprise-wide related matters such as the strategic use of IT. The case focuses on the issues faced by a newly promoted Chief Information Officer, in an environment in which the Chief Executive Officer has articulated the need for a new, transformative, strategic and value creating vision for IT.
Health‐related quality of life in inflammatory bowel disease in a Danish population‐based inception cohort
Authors: Christiansen Lea K , Lo Bobby , Bendtsen Flemming , Vind Ida , Vester-Andersen Marianne K , Burisch Johan
Published: May 2019

Background

Crohn's disease (CD) and ulcerative colitis (UC) are associated with reduced health‐related quality of life (HRQoL), but findings differ between studies. The aim of this study was to analyse the impact of disease activity and social factors on HRQoL.

Method

A total of 513 patients diagnosed with UC and CD between 2003 and 2004, in a population‐based setting, were followed for 7 years. HRQoL was assessed using the Short Form‐12, the Short Inflammatory Bowel Disease (IBD) Questionnaire (SIBDQ), the Work Productivity and Activity Impairment Questionnaire: General Health and a national health survey. Associations were assessed using multiple linear regressions.

Results

A total of 185 of the eligible patients (UC: 107 (50.2%) and CD: 78 (50.3%)) were included. No differences in disease‐specific or generic HRQoL were found between CD and UC patients, and IBD patients did not differ compared with the background population. The majority of CD (73.1%) and UC (85.0%) patients had ‘good’ disease‐specific HRQoL using the SIBDQ. Unemployment for ≥ 3 months occurred more in CD vs UC patients(30.6 vs 15.5%, p = 0.03); however, sick leave for ≥ 3 months did not differ significantly (17.4 vs 11.4%, p = 0.4). Using multiple linear regressions, unemployment, sick leave and disease activity were the factors most frequently associated with reduced HRQoL.

Conclusion

In a population‐based cohort with 7 years of follow‐up, HRQoL did not differ between patients and the background population.
The combine will tell the truth: On precision agriculture and algorithmic rationality
Authors: Miles Christopher
Published: May 2019

Recent technological and methodological changes in farming have led to an emerging set of claims about the role of digital technology in food production. Known as precision agriculture, the integration of digital management and surveillance technologies in farming is normatively presented as a revolutionary transformation. Proponents contend that machine learning, Big Data, and automation will create more accurate, efficient, transparent, and environmentally friendly food production, staving off both food insecurity and ecological ruin. This article contributes a critique of these rhetorical and discursive claims to a growing body of critical literature on precision agriculture. It argues precision agriculture is less a revolution than an evolution, an effort to shore up and intensify the conventional farming system responsible for generating many of the social and environmental problems precision agriculture is presented as solving. While precision agriculture advocates portray it as a radical, even democratic epistemological break with the past, this paper locates truth claims surrounding datafication and algorithmic control in farming within deeper historical contexts of the capitalist rationalization of production and efforts to quantify and automate physical and mental labor. Abjuring the growing cultural tendency to treat algorithmic systems as revolutionary in favor of social and historical dimensions of precision agriculture, can help re-frame the discussion about its design and use around real, socially and ecologically oriented change in farming, and so ensure that the possibilities and benefits of precision agriculture are as evenly and effectively shared as possible.
“There Is a Lot of Community Spirit Going On.” Middle Managers' Stories of Innovation in Home Care Services
Authors: Sørly Rita , Krane Martin Sollund , Bye Geir , Ellingsen May-Britt
Published: May 2019

Background: There is a need for qualitative studies on imposed innovation in home care services in welfare societies. The municipalities are key actors in the field of innovation in the public sector. As innovations often are interpreted to be in conflict with values in health care, we need knowledge on how policy changes and imposed innovations are understood and handled by middle managers working in the sector. Aim: We aim to explore how middle managers react to imposed innovation in health services through their storytelling. The research question was “What can middle managers' stories of imposed innovation tell us about their role in, and some important prerequisites for, innovation processes in municipal health-care services?” Methods: A narrative study of experiences with municipal innovation among middle managers in Norway. In this article, we do a thematic analysis of interviews with seven female middle managers who work in a home care service department. Findings: The study develops an understanding of which frameworks are required within a home care service to meet constant demands for innovation. Innovations are understood by the managers as results of policy changes and new public management demands and as a troublesome burden. We find the prerequisites for implementing innovations to be (1) trust-based management, (2) flexibility and dynamics, (3) continuity of care, and (4) emphasis on competence. These prerequisites are further interpreted in relation to dominant discourses on innovation at the macro, meso, and micro levels within the storytelling contexts. Conclusion: Imposed innovations require a negotiating practice in cross-disciplinary environments at all levels in the organization.
A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL
Authors: Mato Anthony R. , Roeker Lindsey E. , Eyre Toby A. , Nabhan Chadi , Lamanna Nicole , Hill Brian T. , Brander Danielle M. , Barr Paul M. , Lansigan Frederick , Cheson Bruce D. , Singavi Arun K. , Yazdy Maryam Sarraf , Shah Nirav N. , Allan John N. , Bhavsar Erica B. , Rhodes Joanna , Kennard Kaitlin , Schuster Stephen J. , Williams AnnaLynn M. , Skarbnik Alan P. , Goy Andre H. , Goodfriend Julie M. , Dorsey Colleen , Coombs Catherine C. , Tuncer Hande , Ujjani Chaitra S. , Jacobs Ryan , Winter Allison M. , Pagel John M. , Bailey Neil , Schuh Anna , Shadman Mazyar , Sitlinger Andrea , Weissbrot Hanna , Muralikrishnan Sivraj , Zelenetz Andrew , Kirkwood Amy A. , Fox Christopher P.
Published: May 2019

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.
Solvent-mediated extraction of fatty acids in bilayer oil paint models: a comparative analysis of solvent application methods
Authors: Baij Lambert , Astefanei Alina , Hermans Joen , Brinkhuis Francine , Groenewegen Heleen , Chassouant Louise , Johansson Sofia , Corthals Garry , Tokarski Caroline , Iedema Piet , Keune Katrien
Published: May 2019

The impact of solvent exposure on oil paintings and the differences between solvent application methods are longstanding topics in cleaning studies. Solvent exposure is ideally kept to a minimum, because solvent swelling can lead to the extraction and displacement of reactive paint components. In particular, important concerns are fatty acids displacement resulting in metal soap formation and embrittlement of paint due to solvent exposure. In this study, the extraction of a saturated fatty acid (SFA) marker and the formation of zinc soaps were monitored to measure the impact of solvent cleaning on tailored bilayer model systems for aged oil paint. Three methods of solvent application were compared: cotton swab, rigid gel and Evolon tissue (with different solvent loading). The samples were analysed by surface acoustic wave nebulization mass spectrometry (SAWN-MS) and thermally-assisted hydrolysis and methylation pyrolysis gas chromatography mass spectrometry (THM-Py-GC/MS) by comparing the calculated margaric:palmitic acid (

$$\text {C}_{17}{:}\text {C}_{16}$$

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17

:

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16

) ratio determined in the extracts (taken from the swab, gel or Evolon tissue). We conclude that both swab cleaning and squeezed Evolon tissue application result in comparable SFA extraction. The rigid gel and Evolon with controlled solvent-loading limit the amount of SFA extraction. The distribution of

$$\text {C}_{17}$$

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17

after solvent application was visualised using static Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) on cross sections, showing that

$$\text {C}_{17}$$

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17

redistribution took place in all cases where solvent was applied. Crystalline zinc soaps formation was not observed after 5 min of ethanol exposure in the embedded cross-sections with imaging ATR-FTIR, indicating that solvent exposure does not immediately trigger the formation of crystalline metal soaps. However, significant zinc soap formation was found after 30 min of ethanol exposure using Evolon tissue without controlled loading. This study contributes to a better understanding of the impact of different methods of solvent application on oil paintings and highlights important differences between these methods.
Clinician Report of Oral Oncolytic Symptoms and Adherence Obtained via a Patient-Reported Outcome Measure (PROM)
Authors: Nachar Victoria R. , Farris Karen , Beekman Katie , Griggs Jennifer , Hough Shannon , Mackler Emily
Published: May 2019

PURPOSE

Patient-reported outcome measures (PROMs) for symptom monitoring during cancer therapy have been shown to have a positive impact on outcomes. These findings have primarily been shown for patients receiving intravenous chemotherapy. In addition, there is known discordance between physician reporting of symptoms and patient self-report. This initiative sought to describe patient-reported symptom burden and medication adherence and to indicate the degree of PROM results being discussed with the provider as indicated by documentation in the medical record for patients taking oral oncolytic therapy.

METHODS

The Michigan Oncology Quality Consortium (MOQC) PROM, which included symptom ratings, medication adherence, and patient confidence in self-management, was completed during outpatient visits and compared with corresponding data documented in the electronic medical record (EMR).

RESULTS

There were 82 completed PROMs. Approximately half included at least one symptom rated as severe (46%). Sixty-five percent of reported severe symptoms were documented in the EMR. Patient-reported moderate-to-severe pain was most likely to be documented in the EMR (100%), whereas patient-reported moderate-to-severe depression and anxiety were least likely to be documented (21%). Of the total symptoms documented, grading of symptom severity matched that of the patients’ own report for 11% of severe symptoms. Adherence to oral oncolytics was excellent for 63% of patients, and patient adherence was documented in 7% of provider notes.

CONCLUSION

Patients frequently reported moderate-to-severe symptoms, and approximately 40% of patients reported nonadherence. Clinician report (documented in the EMR) of the patient symptom burden, symptom severity, and adherence to oral oncolytic therapy was not consistent with the patients’ self-report. Use of a PROM for patients taking oral oncolytics has the opportunity to improve symptom management and medication adherence.
The Management and Prevention of Anal Squamous Cell Carcinoma
Authors: Eng Cathy , Messick Craig , Glynne-Jones Rob
Published: May 2019

Our aim is to discuss the current established management of care and associated prevention strategies of anal squamous cell carcinoma (SCCA). In general, the development of SCCA is commonly linked to a prior history of HPV. Unfortunately, HPV vaccination continues to be underutilized in the United States versus other countries. Increased acknowledgment of the importance of HPV vaccination as an anticancer vaccine should be encouraged. The present standard of care is primary chemoradiotherapy (CRT), which results in a high level of disease control for small, early-stage SCCA. More advanced cancers still fare poorly with this treatment, and the disease relapses locoregionally in the majority of cases (30%–50% of patients), resulting in an abdominoperineal resection. Current treatment recommendations are associated with substantial morbidity; alternative radiation doses and/or novel combinations of agents with CRT are needed to improve quality of life and oncologic outcomes. Cytotoxic chemotherapy remains the standard of care for treatment-naïve patients with metastatic disease, with a possible new treatment paradigm of carboplatin/weekly paclitaxel. In addition, immune checkpoint inhibition appears to have a promising role in the setting of patients with refractory disease. Several clinical trials with immunotherapeutic and vaccine approaches for locally advanced and metastatic anal cancer are ongoing, as are HPV-agnostic umbrella trials. Whenever possible, clinical trial enrollment is always encouraged for further therapeutic development in the setting of a rare cancer, given the potentially substantial global impact for other HPV-associated malignancies.
Translating IDEA to Practice and Beyond: Managing Stage II and III Colon Cancer
Authors: Gill Sharlene , Meyerhardt Jeffrey A. , Arun Monica , Veenstra Christine M.
Published: May 2019

Adjuvant fluoropyrimidine-based chemotherapy has been the standard of care for resected stage III colon cancer since the 1990s; the evolution from 12 to 6 months of fluoropyrimidine therapy and the addition of oxaliplatin to fluoropyrimidine therapy have led to the current accepted standard. However, controversies remain. What is the benefit of adjuvant chemotherapy in stage II disease, and in whom? What is the optimal duration of adjuvant chemotherapy? How should patients with early-stage colon cancer be followed after surgery and adjuvant treatment? Recent evidence has emerged to help inform these important questions, including the International Duration Evaluation of Adjuvant therapy (IDEA) collaboration, which is the largest, prospective study in colon cancer with 12,834 patients. This review discusses current and future risk stratification strategies in stage II disease: the optimal duration of adjuvant oxaliplatin-containing chemotherapy in stage II and III disease according to the IDEA study, and the recent evidence and updated recommendations for surveillance of early-stage colon cancer after resection.
Conceptual Framework for Therapeutic Development Beyond Anti–PD-1/PD-L1 in Urothelial Cancer
Authors: Grivas Petros , Drakaki Alexandra , Friedlander Terence W. , Sonpavde Guru
Published: May 2019

Platinum-based chemotherapy has been the standard of care in advanced urothelial cancer, but long-term outcomes have remained poor. Immune checkpoint inhibitors, with their favorable toxicity profiles and noteworthy efficacy, have steered a new era in advanced urothelial cancer, with five agents targeting the PD-1/PD-L1 pathway approved by the U.S. Food and Drug Administration (FDA). However, most patients do not achieve response, whereas immunotherapy-related adverse events may cause morbidity, increased health care use, and—rarely—mortality. Therefore, there is an urgent need for additional therapeutic modalities across the disease spectrum. A plethora of clinical trials are ongoing in various disease settings, including chemotherapy regimens, radiotherapy, antibody-drug conjugates, agents targeting additional immune checkpoint pathways, vaccine, cytokines, adoptive cell therapies, as well as targeted and anti-angiogenic agents. Two agents, enfortumab vedotin and erdafitinib, have breakthrough designation by the FDA but are not approved yet (at the time of this paper's preparation). Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials. Evaluation of new treatments has met with substantial challenges for many reasons, for example, molecular heterogeneity, clonal evolution, and genomic instability. In the era of precision molecular medicine, and because patients do not respond uniformly to current therapies, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. Here, we review current updates and future directions of experimental therapeutics in urothelial cancer, including examples (but not an exhaustive list) of ongoing clinical trials.
A Practical Guide to Geriatric Syndromes in Older Adults With Cancer: A Focus on Falls, Cognition, Polypharmacy, and Depression
Authors: Magnuson Allison , Sattar Schroder , Nightingale Ginah , Saracino Rebecca , Skonecki Emily , Trevino Kelly M.
Published: May 2019

Geriatric syndromes are multifactorial conditions that are prevalent in older adults. Geriatric syndromes are believed to develop when an individual experiences accumulated impairments in multiple systems that compromise their compensatory ability. In older adults with cancer, the presence of a geriatric syndrome is common and may increase the complexity of cancer treatment. In addition, the physiologic stress of cancer and cancer treatment may precipitate or exacerbate geriatric syndromes. Common geriatric syndromes include falls, cognitive syndromes and delirium, depression, and polypharmacy. In the oncology setting, the presence of geriatric syndromes is relevant; falls and cognitive problems have been shown to be predictive of chemotherapy toxicity and overall survival. Polypharmacy and depression are more common in older adults with cancer compared with the general geriatric population. Multiple screening tools exist to identify falls, cognitive problems, polypharmacy, and depression in older adults and can be applied to the oncology setting to identify patients at risk. When recognized, several interventions exist that could be considered for this vulnerable population. We review the available evidence of four geriatric syndromes in the oncology setting, including clinical implications, validated screening tools, potential supportive care, and therapeutic interventions.
Debating the Optimal Approach to Nodal Management After Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer
Authors: Carter Stacey , Neuman Heather , Mamounas Eleftherios P. , Bedrosian Isabelle , Moulder Stacy , Montero Alberto J. , Jagsi Reshma
Published: May 2019

Greater use of neoadjuvant chemotherapy in patients with breast cancer has led surgeons and radiation oncologists to have frequent encounters with women with upfront node-positive disease and a clinical complete response. These cases raise many important questions about what the optimal locoregional management should be to minimize recurrence risk while minimizing treatment-related toxicities. A particular point of debate is whether all patients who are known to have had node-positive disease before neoadjuvant chemotherapy should receive complete axillary lymph node dissection (ALND) if they have had a complete clinical and radiologic response. In this article, we present arguments and evidence in favor of and against axillary dissection after a complete response to neoadjuvant chemotherapy, followed by a brief data-driven review of implications for adjuvant radiotherapy in this context. We conclude that as trials continue to gather more evidence to guide decisions in the future, we must encourage patients to enroll in clinical trials when eligible, and otherwise support them to make decisions that are informed and congruent with their personal values in areas where there is clinical equipoise.
Updates in Local-Regionally Advanced Non–Small Cell Lung Cancer
Authors: Tsao Anne S. , Jolly Shruti , Lee Jay M.
Published: May 2019

The landscape for therapy in local-regionally advanced non–small cell lung cancer (NSCLC) has shifted dramatically in the last year as a result of the PACIFIC trial, which demonstrated a significant survival benefit with the addition of 1 year of durvalumab after concurrent chemoradiation. This is a new standard of care for unresectable local-regionally advanced NSCLC and is the first trial to show that immunotherapy can increase survival in earlier-stage NSCLC. Several clinical trials are underway or in development to explore the role of adding immunotherapy to concurrent chemoradiation, followed by a year of immunotherapy or to even replace chemotherapy in this treatment paradigm. In resectable disease, adjuvant chemotherapy is still the standard of care for stage IB (tumors ≥ 4 cm) through stage III disease. However, new studies are investigating the role of adding immunotherapy to neoadjuvant chemotherapy or as adjuvant therapy for 1 year after resection. Molecular profiling for early-stage disease is not currently the standard of care, but several national clinical trials are studying the benefit of adding adjuvant-targeted therapies. This article will detail the current standard practices in early-stage and local-regionally advanced NSCLC and describe the evolving strategies that are under investigation that may further refine our current practice.
Immunotherapy in Gynecologic Cancers: What We Know Now and Where We Are Headed
Authors: Levinson Kimberly , Dorigo Oliver , Rubin Krista , Moore Kathleen
Published: May 2019

Immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs), has been transformative in both solid tumor and hematologic malignancies. Patients with previously terminal illnesses have experienced profound responses of great durability with these agents, fueling excitement among patients and providers regarding their use. Unfortunately, the gains seen in some solid tumors have not been replicated in a large percentage of patients with gynecologic cancer. This review focuses on the clinical benefits seen to date, toxicities and management when using ICIs, ways to improve prediction of who should receive immunotherapy, and a discussion of next-generation immunotherapy with cellular therapeutics and how these might relate to gynecologic cancers.
The Impact of Big Data Research on Practice, Policy, and Cancer Care
Authors: Chambers David A. , Amir Eitan , Saleh Ramy R. , Rodin Danielle , Keating Nancy L. , Osterman Travis J. , Chen James L.
Published: May 2019

The concept of “big data” research—the aggregation and analysis of biologic, clinical, administrative, and other data sources to drive new advances in biomedical knowledge—has been embraced by the cancer research enterprise. Although much of the conversation has concentrated on the amalgamation of basic biologic data (e.g., genomics, metabolomics, tumor tissue), new opportunities to extend potential contributions of big data to clinical practice and policy abound. This article examines these opportunities through discussion of three major data sources: aggregated clinical trial data, administrative data (including insurance claims data), and data from electronic health records. We will discuss the benefits of data use to answer key oncology practice and policy research questions, along with limitations inherent in these complex data sources. Finally, the article will discuss overarching themes across data types and offer next steps for the research, practice, and policy communities. The use of multiple sources of big data has the promise of improving knowledge and providing more accurate data for clinicians and policy decision makers. In the future, optimization of machine learning may allow for current limitations of big data analyses to be attenuated, thereby resulting in improved patient care and outcomes.
Relapsed and Refractory Classical Hodgkin Lymphoma: Keeping Pace With Novel Agents and New Options for Salvage Therapy
Authors: Moskowitz Alison J. , Herrera Alex F. , Beaven Anne W.
Published: May 2019

The management of relapsed and refractory classic Hodgkin lymphoma (HL) has changed substantially since the approval of brentuximab vedotin (BV) and the checkpoint inhibitors nivolumab and pembrolizumab. For patients progressing after frontline treatment, second-line therapy followed by consolidation with autologous stem cell transplant (ASCT) remains the standard of care; however, although traditional combination chemotherapy regimens previously represented the only options for salvage, BV is now routinely incorporated into second-line therapy, and studies are evaluating checkpoint inhibitors in this setting as well. After ASCT, BV maintenance improves progression-free survival for patients at higher-risk, and studies are evaluating the role of post-ASCT maintenance with checkpoint inhibitors. Management of HL that progresses after ASCT remains a challenge. Although many patients achieve prolonged disease control with checkpoint inhibitors, the majority eventually progress and require additional therapy. Newer approaches, including CD30-directed chimeric antigen receptor–T-cell therapy, appear promising. Furthermore, allogeneic stem cell transplant remains an important consideration. Altogether, BV and checkpoint inhibitors have improved survival for patients with relapsed and refractory HL. However, the ideal place for these drugs in the treatment course of HL is still under investigation. Ongoing studies testing novel combinations and assessing for prognostic and predictive markers will ultimately define the optimal setting for these drugs in the treatment of relapsed and refractory HL.
Using Big Data and Predictive Analytics to Determine Patient Risk in Oncology
Authors: Parikh Ravi B. , Gdowski Andrew , Patt Debra A. , Hertler Andrew , Mermel Craig , Bekelman Justin E.
Published: May 2019

Big data and predictive analytics have immense potential to improve risk stratification, particularly in data-rich fields like oncology. This article reviews the literature published on use cases and challenges in applying predictive analytics to improve risk stratification in oncology. We characterized evidence-based use cases of predictive analytics in oncology into three distinct fields: (1) population health management, (2) radiomics, and (3) pathology. We then highlight promising future use cases of predictive analytics in clinical decision support and genomic risk stratification. We conclude by describing challenges in the future applications of big data in oncology, namely (1) difficulties in acquisition of comprehensive data and endpoints, (2) the lack of prospective validation of predictive tools, and (3) the risk of automating bias in observational datasets. If such challenges can be overcome, computational techniques for clinical risk stratification will in short order improve clinical risk stratification for patients with cancer.
Oligometastatic Prostate Cancer: A Shrinking Subset or an Opportunity for Cure?
Authors: Rao Arpit , Vapiwala Neha , Schaeffer Edward M. , Ryan Charles J.
Published: May 2019

Oligometastatic prostate cancer (OMPC), generally defined by presence of five or fewer metastatic sites on imaging, represents a transitional state between localized and widespread metastatic disease and encompasses a wide spectrum of disease biologies and clinical behaviors. A collaborative effort is ongoing to determine the genomics of OMPC. The prevalence of OMPC varies significantly in the literature and is likely to change further as substantial improvements in imaging improve our ability to reclassify a subset of patients with biochemical recurrence by conventional imaging as OMPC and another subset from OMPC to polymetastatic disease. The mainstay of OMPC treatment remains systemic therapy, either with androgen-deprivation therapy (ADT) alone or in combination with other agents (docetaxel, abiraterone, etc.). Focal therapies, including resection or radiotherapy (RT), to the primary tumor have demonstrated an improvement in outcomes, including failure-free survival in several retrospective studies. RT to the prostate has specifically demonstrated an overall survival (OS) advantage in patients with low-volume disease in a clinical trial. Improvement in outcomes has been observed with focal therapies for retroperitoneal and more distant metastatic sites in retrospective studies. Advancements in our understanding of the biology, imaging modalities, and treatments may allow for aggressive multimodality therapies in an effort to obtain deeper responses and, potentially, cures for selected patients with OMPC with favorable clinicopathologic characteristics. Participation in clinical trials or institutional registries is strongly encouraged for patients with OMPC who opt for an aggressive multimodality approach.
The Evolving Role of Prostate-Specific Membrane Antigen–Based Diagnostics and Therapeutics in Prostate Cancer
Authors: Dorff Tanya B. , Fanti Stefano , Farolfi Andrea , Reiter Robert E. , Sadun Taylor Y. , Sartor Oliver
Published: May 2019

Prostate-specific membrane antigen (PSMA)–based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, 68Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from 177Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.
Approaches to High-Risk Resected Stage II and III Melanoma
Authors: Yushak Melinda , Mehnert Janice , Luke Jason , Poklepovic Andrew
Published: May 2019

Over the last decade, several therapies, including both targeted and immune checkpoint inhibitors, have dramatically changed the treatment landscape for patients with metastatic melanoma. These same therapies are now being used in the adjuvant setting with the hope of delaying or preventing the development of metastatic disease. Although phase III trials have shown a clear benefit for patients with resected bulky nodal disease, treatment decisions for patients with earlier-stage (high-risk stage II and stage IIIA) melanoma in the adjuvant setting are less straightforward given the small number of patients studied so far. Among patients with stage IIIB and worse disease, both targeted and immune checkpoint inhibitors have shown benefit in recurrence-free survival. Although a head-to-head comparison has not been completed, patient and tumor characteristics can guide the optimal treatment of an individual.
Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?
Authors: Fares Charlene M. , Van Allen Eliezer M. , Drake Charles G. , Allison James P. , Hu-Lieskovan Siwen
Published: May 2019

The emergence of immune checkpoint blockade therapies over the last decade has transformed cancer treatment in a wide range of tumor types. Unprecedented and durable clinical responses in difficult-to-treat cancer histologies have been observed. However, despite these promising long-term responses, the majority of patients fail to respond to immune checkpoint blockade, demonstrating primary resistance. Additionally, many of those who initially respond to treatment eventually experience relapse secondary to acquired resistance. Both primary and acquired resistance are a result of complex and constantly evolving interactions between cancer cells and the immune system. Many mechanisms of resistance have been characterized to date, and more continue to be uncovered. By elucidating and targeting mechanisms of resistance, treatments can be tailored to improve clinical outcomes. This review will discuss the landscape of immune checkpoint blockade response data, different resistance mechanisms, and potential therapeutic strategies to overcome resistance.
Preparing Fellows for Graduation: Perspectives on Career Guidance
Authors: LaCasce Ann , Graff Stephanie , Gao Jennifer , Close Julia , Boulmay Brian
Published: May 2019

At the completion of a hematology/oncology fellowship, trainees are likely to enter into a career differing from the one modeled by the faculty providing mentorship and teaching during training. Fellows benefit from open communication with regard to career goals and opportunities starting early in training. To ensure honesty in the process, program directors must be accepting and supportive of house staff selecting careers different from those of the training environment. Following identification of a long-term career goal, program directors may facilitate a smooth transition to the early career through thoughtful inclusion of alternative experiences and additional mentors. Barriers exist, including funding and limited time in training while completing educational requirements, which may make inclusion of the experiences a challenge.
Community-Academic Partnerships: Approaches to Engagement
Authors: Noel Lailea , Phillips Farya , Tossas-Milligan Katherine , Spear Krista , Vanderford Nathan L. , Winn Robert A. , Vanderpool Robin C. , Eckhardt S. Gail
Published: May 2019

Current public health problems such as cancer have an expansive set of lifestyle and social circumstances that affect the cause and course of the disease. In response, over the past 7 years, the National Cancer Institute (NCI) has recognized the important role that cancer centers play in their community and has gradually increased the requirements and stringency of these sections in the Cancer Center Support Grant guidelines to include a plan for community outreach and engagement. Developing sustainable community-academic partnerships is an essential factor for the successful dissemination and implementation of promising interventions and programs aimed at decreasing barriers and improving cancer outcomes. Understanding how best to facilitate linkages and collaboration can expedite translation of research knowledge into practice and allow more evidence-based improvements to be implemented into practice as well as influence research agendas. This article will examine several examples of successful community-academic partnerships focused on cancer prevention and control and explore lessons learned.
Perceptions of Patients With Breast and Colon Cancer of the Management of Cancer-Related Pain, Fatigue, and Emotional Distress in Community Oncology
Authors: Smith Tenbroeck G. , Troeschel Alyssa N. , Castro Kathleen M. , Arora Neeraj K. , Stein Kevin , Lipscomb Joseph , Brawley Otis W. , McCabe Ryan M. , Clauser Steven B. , Ward Elizabeth
Published: May 2019

PURPOSE

Pain, fatigue, and distress are common among patients with cancer but are often underassessed and undertreated. We examine the prevalence of pain, fatigue, and emotional distress among patients with cancer, as well as patient perceptions of the symptom care they received.

PATIENTS AND METHODS

Seventeen Commission on Cancer–accredited cancer centers across the United States sampled patients with local/regional breast (82%) or colon (18%) cancer. We received 2,487 completed surveys (61% response rate).

RESULTS

Of patients, 76%, 78%, and 59% reported talking to a clinician about pain, fatigue, and distress, respectively, and 70%, 61%, and 54% reported receiving advice. Sixty-one percent of patients experienced pain, 74% fatigue, and 46% distress. Among those patients experiencing each symptom, 58% reported getting the help they wanted for pain, 40% for fatigue, and 45% for distress. Multilevel logistic regression models revealed that patients experiencing symptoms were significantly more likely to have talked about and received advice on coping with these symptoms. In addition, patients who were receiving or recently completed curative treatment reported more symptoms and better symptom care than did those who were further in time from curative treatment.

CONCLUSION

In our sample, 30% to 50% of patients with cancer in community cancer centers did not report discussing, getting advice, or receiving desired help for pain, fatigue, or emotional distress. This finding suggests that there is room for improvement in the management of these three common cancer-related symptoms. Higher proportions of talk and advice among those experiencing symptoms imply that many discussions may be patient initiated. Lower rates of talk and advice among those who are further in time from treatment suggest the need for more assessment among longer-term survivors, many of whom continue to experience these symptoms. These findings seem to be especially important given the high prevalence of these symptoms in our sample.
Unpredictable Injectate Spread of the Erector Spinae Plane Block in Human Cadavers
Authors: Dautzenberg Karin H. W. , Zegers Marissa J. , Bleeker Chris P. , Tan Edward C. T. H. , Vissers Kris C. P. , van Geffen Geert-Jan , van der Wal Selina E. I.
Published: May 2019

We performed bilateral ultrasound-guided erector spinae plane blocks at the second and eighth thoracic vertebrae in 11 fresh frozen cadavers. Methylene blue dye spread variably and extensively deep to the erector spinae muscles fascia with involvement of the spinal rami and paravertebral space in 1 of 11 cadavers when injected at the eighth thoracic vertebra, and in 4 of 11 cadavers at the second thoracic vertebra, with crossover to the contralateral side of the spine. Our study demonstrates that in cadavers, an erector spinae plane block follows the fascial planes with unpredictable spread, which might explain its varying clinical efficacy.