Publications by authors named "Jennifer Malin"

125 Publications

Neural specification, targeting, and circuit formation during visual system assembly.

Proc Natl Acad Sci U S A 2021 07;118(28)

Department of Biology, New York University, New York, NY 10003;

Like other sensory systems, the visual system is topographically organized: Its sensory neurons, the photoreceptors, and their targets maintain point-to-point correspondence in physical space, forming a retinotopic map. The iterative wiring of circuits in the visual system conveniently facilitates the study of its development. Over the past few decades, experiments in have shed light on the principles that guide the specification and connectivity of visual system neurons. In this review, we describe the main findings unearthed by the study of the visual system and compare them with similar events in mammals. We focus on how temporal and spatial patterning generates diverse cell types, how guidance molecules distribute the axons and dendrites of neurons within the correct target regions, how vertebrates and invertebrates generate their retinotopic map, and the molecules and mechanisms required for neuronal migration. We suggest that basic principles used to wire the fly visual system are broadly applicable to other systems and highlight its importance as a model to study nervous system development.
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http://dx.doi.org/10.1073/pnas.2101823118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285955PMC
July 2021

Neuronal diversity and convergence in a visual system developmental atlas.

Nature 2021 01 4;589(7840):88-95. Epub 2020 Nov 4.

Department of Biology, New York University, New York, NY, USA.

Deciphering how neuronal diversity is established and maintained requires a detailed knowledge of neuronal gene expression throughout development. In contrast to mammalian brains, the large neuronal diversity of the Drosophila optic lobe and its connectome are almost completely characterized. However, a molecular characterization of this neuronal diversity, particularly during development, has been lacking. Here we present insights into brain development through a nearly complete description of the transcriptomic diversity of the optic lobes of Drosophila. We acquired the transcriptome of 275,000 single cells at adult and at five pupal stages, and built a machine-learning framework to assign them to almost 200 cell types at all time points during development. We discovered two large neuronal populations that wrap neuropils during development but die just before adulthood, as well as neuronal subtypes that partition dorsal and ventral visual circuits by differential Wnt signalling throughout development. Moreover, we show that the transcriptomes of neurons that are of the same type but are produced days apart become synchronized shortly after their production. During synaptogenesis we also resolved neuronal subtypes that, although differing greatly in morphology and connectivity, converge to indistinguishable transcriptomic profiles in adults. Our datasets almost completely account for the known neuronal diversity of the Drosophila optic lobes, and serve as a paradigm to understand brain development across species.
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http://dx.doi.org/10.1038/s41586-020-2879-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790857PMC
January 2021

Real-World Outcomes and Value of First-Line Therapy for Metastatic Non-Small Cell Lung Cancer.

Cancer Invest 2020 Nov 27;38(10):608-617. Epub 2020 Oct 27.

Lee N. Newcomer Consulting, LLC, Minneapolis, Minnesota, USA.

Although physicians rely on clinical trial data to guide cancer treatment decisions, patient characteristics and outcomes often differ between real-world and clinical trial populations. We analyzed retrospective clinical data collected from a prior authorization (PA) tool linked with payer claims data to describe outcomes of first-line treatment for metastatic non-small cell lung cancer among 2,108 patients. Duration of therapy was shorter than observed in clinical trials. Healthcare costs and hospitalizations varied substantially by regimen. PA clinical data linked with administrative claims enable head-to-head comparisons of contemporary cancer treatments used in routine clinical practice, which are not available from clinical trials.
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http://dx.doi.org/10.1080/07357907.2020.1827415DOI Listing
November 2020

Measure Scan and Synthesis of Palliative and End-of-Life Process Quality Measures for Advanced Cancer.

JCO Oncol Pract 2021 02 6;17(2):e140-e148. Epub 2020 Aug 6.

Veterans Affairs Greater Los Angeles Health Care System, Center for the Study of Healthcare Innovation, Implementation and Policy, Los Angeles, CA.

Purpose: Monitoring and improving the quality of palliative and end-of-life cancer care remain pressing needs in the United States. Among existing measures that assess the quality of palliative and end-of-life care, many operationalize similar concepts. We identified existing palliative care process measures and synthesized these measures to aid stakeholder prioritization that will facilitate health system implementation in patients with advanced cancer.

Methods: We reviewed MEDLINE/PubMed-indexed articles for process quality measures related to palliative and end-of-life care for patients with advanced cancer, supplemented by expert input. Measures were inductively grouped into "measure concepts" and higher-level groups.

Results: Literature review identified 226 unique measures from 23 measure sources, which we grouped into 64 measure concepts within 12 groups. Groups were advance care planning (11 measure concepts), pain (7), dyspnea (9), palliative care-specific issues (6), other specific symptoms (17), comprehensive assessment (2), symptom assessment (1), hospice/palliative care referral (1), spiritual care (2), mental health (5), information provision (2), and culturally appropriate care (1).

Conclusion: Measure concepts covered the spectrum of care from acute symptom management to advance care planning and psychosocial needs, with variability in the number of measure concepts per group. This taxonomy of process quality measure concepts can be used by health systems seeking stakeholder input to prioritize targets for improving palliative and end-of-life care quality in patients with advanced cancer.
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http://dx.doi.org/10.1200/OP.20.00240DOI Listing
February 2021

Charting the Course: Use of Clinical Pathways to Improve Value in Cancer Care.

Authors:
Jennifer L Malin

J Clin Oncol 2020 02 5;38(4):367-371. Epub 2019 Dec 5.

UnitedHealthcare, Minnetonka, MN.

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http://dx.doi.org/10.1200/JCO.19.01482DOI Listing
February 2020

versus .

Elife 2018 03 27;7. Epub 2018 Mar 27.

Department of Biology, New York University, New York, United States.

A long non-coding RNA molecule called is a driver of tumor development.
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http://dx.doi.org/10.7554/eLife.36030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871327PMC
March 2018

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

J Natl Compr Canc Netw 2018 02;16(2):162-169

White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; =.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; =.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.
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http://dx.doi.org/10.6004/jnccn.2017.7033DOI Listing
February 2018

Smoking Status and Survival Among a National Cohort of Lung and Colorectal Cancer Patients.

Nicotine Tob Res 2019 03;21(4):497-504

Tobacco Research and Treatment Center, and the Mongan Institute for Health Policy Center, Massachusetts General Hospital, Boston, MA.

Introduction: The purpose of this study was to explore the association of smoking status and clinically relevant duration of smoking cessation with long-term survival after lung cancer (LC) or colorectal cancer (CRC) diagnosis. We compared survival of patients with LC and CRC who were never-smokers, long-term, medium-term, and short-term quitters, and current smokers around diagnosis.

Methods: We studied 5575 patients in Cancer Care Outcomes Research and Surveillance (CanCORS), a national, prospective observational cohort study, who provided smoking status information approximately 5 months after LC or CRC diagnosis. Smoking status was categorized as: never-smoker, quit >5 years prior to diagnosis, quit between 1-5 years prior to diagnosis, quit less than 1 year before diagnosis, and current smoker. We examined the relationship between smoking status around diagnosis with mortality using Cox regression models.

Results: Among participants with LC, never-smokers had lower mortality risk compared with current smokers (HR 0.71, 95% CI 0.57 to 0.89). Among participants with CRC, never-smokers had a lower mortality risk as compared to current smokers (HR 0.79, 95% CI 0.64 to 0.99).

Conclusions: Among both LC and CRC patients, current smokers at diagnosis have higher mortality than never-smokers. This effect should be further studied in the context of tumor biology. However, smoking cessation around the time of diagnosis did not affect survival in this sample.

Implications: The results from our analysis of patients in the CanCORS consortium, a large, geographically diverse cohort, show that both LC and CRC patients who were actively smoking at diagnosis have worse survival as compared to never-smokers. While current smoking is detrimental to survival, cessation upon diagnosis may not mitigate this risk.
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http://dx.doi.org/10.1093/ntr/nty012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609879PMC
March 2019

Effect and Efficiency of an Embedded Palliative Care Nurse Practitioner in an Oncology Clinic.

J Oncol Pract 2017 09 16;13(9):e792-e799. Epub 2017 Aug 16.

Greater Los Angeles Veterans Affairs Healthcare System; University of California at Los Angeles (UCLA); UCLA Center for Integrative Oncology; UCLA Health, Los Angeles, CA; and Anthem, Indianapolis, IN.

Purpose: To test a simultaneous care model for palliative care for patients with advanced cancer by embedding a palliative care nurse practitioner (NP) in an oncology clinic.

Methods: We evaluated the effect of the intervention in two oncologists' clinics beginning March 2014 by using implementation strategies, including use of a structured referral mechanism, routine symptom screening, integration of a psychology-based cancer supportive care center, implementation team meetings, team training, and a metrics dashboard for continuous quality improvement. After 1 year of implementation, we evaluated key process and outcome measures for supportive oncology and efficiency of the model by documenting tasks completed by the NP during a subset of patient visits and time-motion studies.

Results: Of approximately 10,000 patients with active cancer treated in the health system, 2,829 patients had advanced cancer and were treated by 42 oncologists. Documentation of advance care planning increased for patients of the two intervention oncologists compared with patients of the other oncologists. Hospice referral before death was not different at baseline, but was significantly higher for patients of intervention oncologists compared with patients of control oncologists (53% v 23%; P = .02) over the intervention period. Efficiency evaluation revealed that approximately half the time spent by the embedded NP potentially could have been completed by other staff (eg, a nurse, a social worker, or administrative staff).

Conclusion: An embedded palliative care NP model using scalable implementation strategies can improve advance care planning and hospice use among patients with advanced cancer.
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http://dx.doi.org/10.1200/JOP.2017.020990DOI Listing
September 2017

Physician variation in lung cancer treatment at the end of life.

Am J Manag Care 2017 Apr;23(4):216-223

Cedars-Sinai Medical Care Foundation, Los Angeles, CA. E-mail:

Objectives: To determine whether a treating oncologist's characteristics are associated with variation in use of chemotherapy for patients with advanced non-small cell lung cancer (aNSCLC) at the end of life.

Study Design: Retrospective cohort.

Methods: Using the 2009 Surveillance, Epidemiology, and End Results-Medicare database, we studied chemotherapy receipt within 30 days of death among Medicare enrollees who were diagnosed with aNSCLC between 1999 and 2006, received chemotherapy, and died within 3 years of diagnosis. A multilevel model was constructed to assess the contribution of patient and physician characteristics and geography to receiving chemotherapy within 30 days of death.

Results: Among 21,894 patients meeting eligibility criteria, 43.1% received chemotherapy within 30 days of death. In unadjusted bivariate analyses, female sex, Asian or black race, older age, and a greater number of comorbid diagnoses predicted lower likelihood of receiving chemotherapy at the end of life (P ≤.038 for all comparisons). Adjusting for patient and physician characteristics, physicians in small independent practices were substantially more likely than those employed in other practice models, particularly academic practices or nongovernment hospitals, to order chemotherapy for a patient in the last 30 days of life (P <.001 for all comparisons); female physicians were less likely than males to prescribe such treatment (P = .04).

Conclusions: Patients receiving care for aNSCLC in small independent oncology practices are more likely to receive chemotherapy in the last 30 days of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762116PMC
April 2017

Payer View of High-Quality Clinical Pathways for Cancer.

J Oncol Pract 2017 03;13(3):148-150

UnitedHealthcare, Minnetonka, MN.

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http://dx.doi.org/10.1200/JOP.2016.020503DOI Listing
March 2017

Reducing Overuse of Colony-Stimulating Factors in Patients With Lung Cancer Receiving Chemotherapy: Evidence From a Decision Support-Enabled Program.

J Oncol Pract 2017 04 4;13(4):e337-e345. Epub 2017 Mar 4.

HealthCore, Wilmington, DE; Anthem, Woodland Hills, CA; and AIM Specialty Health, Deerfield, IL.

Purpose: Colony-stimulating factors (CSFs) are frequently overused for the primary prevention of febrile neutropenia (FN) in patients receiving chemotherapy.

Methods: A retrospective cohort study design was used to analyze commercial claims data in adults with lung cancer initiated on chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented at oncology practices in phases across 14 US states. Patients were assigned to intervention and nonintervention states according to whether they resided in service areas where the tool had been implemented. Patients were followed up to 6 months after initiating chemotherapy. Difference in pre- and postimplementation CSF use and FN incidence rates were compared with the use of difference-in-differences (DID) models that were adjusted for baseline FN risk factors.

Results: The study population of 3,467 patients (intervention states: pre, 707; post, 1,150; nonintervention states: pre, 636; post, 974) showed no significant differences in FN risk factors at baseline. In adjusted results before and after implementation, CSF use decreased from 48.4% to 35.6% in the intervention states versus 43.2% to 44.4% in the nonintervention states (DID, -8.7%; 95% CI, -14.65% to -2.67%; P ≤ .001). The rates of FN were consistent for both groups in both periods, with no statistical difference in trend for the intervention (2.8% to 4.3%) versus the nonintervention (3.1% to 5.1%) states (DID, -0.13; 95% CI, -0.35 to 0.10; P = .927).

Conclusion: These findings demonstrate that a decision support-enabled utilization management tool can improve risk-appropriate, guideline-adherent CSF use in patients with lung cancer.
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http://dx.doi.org/10.1200/JOP.2017.020867DOI Listing
April 2017

Differences in Health Care Use and Costs Among Patients With Cancer Receiving Intravenous Chemotherapy in Physician Offices Versus in Hospital Outpatient Settings.

J Oncol Pract 2017 01 15;13(1):e37-e46. Epub 2016 Nov 15.

HealthCore, Wilmington, DE; Genentech, San Francisco, CA; Anthem, Indianapolis, IN; and New Mexico Cancer Center, Albuquerque, NM.

Purpose: The current shift in site of care from community oncology practices to the hospital outpatient department to deliver oncology services may have significant implications for the economic and clinical outcomes of cancer care. Therefore, this study compares health care use and costs among patients with cancer receiving intravenous (IV) chemotherapy in physician offices (PO) versus in hospital outpatient settings (HOP).

Methods: This retrospective study, which was based on medical and pharmacy claims data, included patients (age, 18 to 64 years) initiating IV chemotherapy/biologic treatment between January 1, 2006, and August 31, 2012, who were diagnosed with early or metastatic breast cancer, metastatic lung cancer, metastatic colorectal cancer, or non-Hodgkin lymphoma or chronic lymphocytic leukemia. Patients were assigned to PO or HOP groups on the basis of where they received > 95% of their IV cancer therapy.

Results: The study sample included 18,740 patients (12,899 PO; 5,841 HOP) who had a mean age of 51.6 years and a Deyo-Charlson Comorbidity Index score of 5.37. Overall office visits (21.8 ± 13.8 PO v 21.2 ± 12.9, P < .005) and outpatient services (50.8 ± 35.5 PO v 48.5 ± 33.6, P < .001) were higher in the PO group than in the HOP group. Cancer-related inpatient hospitalizations (0.6 ± 1.2 PO v 0.7 ± 1.4 HOP, P = .002) were lower in the PO group than in the HOP group. Although quality-of-care metrics were similar between the HOP and PO groups, follow-up all-cause costs ($82,773 PO v $122,473 HOP) and cancer-related health care costs ($69,037 PO v $108,177 HOP) were higher in the HOP group than in the PO group.

Conclusion: Despite similar resource use, all-cause and cancer-related health care costs in HOP were significantly higher compared with those in PO settings.
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http://dx.doi.org/10.1200/JOP.2016.012930DOI Listing
January 2017

Palliative Care Specialist Consultation Is Associated With Supportive Care Quality in Advanced Cancer.

J Pain Symptom Manage 2016 10 9;52(4):507-514. Epub 2016 Jul 9.

Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, USA; VA Palo Alto Healthcare System, Palo Alto, California, USA; Stanford School of Medicine, Stanford, California, USA.

Context: Although recent randomized controlled trials support early palliative care for patients with advanced cancer, the specific processes of care associated with these findings and whether these improvements can be replicated in the broader health care system are uncertain.

Objectives: The aim of this study was to evaluate the occurrence of palliative care consultation and its association with specific processes of supportive care in a national cohort of Veterans using the Cancer Quality ASSIST (Assessing Symptoms Side Effects and Indicators of Supportive Treatment) measures.

Methods: We abstracted data from 719 patients' medical records diagnosed with advanced lung, colorectal, or pancreatic cancer in 2008 over a period of three years or until death who received care in the Veterans Affairs Health System to evaluate the association of palliative care specialty consultation with the quality of supportive care overall and by domain using a multivariate regression model.

Results: All but 54 of 719 patients died within three years and 293 received at least one palliative care consult. Patients evaluated by a palliative care specialist at diagnosis scored seven percentage points higher overall (P < 0.001) and 11 percentage points higher (P < 0.001) within the information and care planning domain compared with those without a consult.

Conclusion: Early palliative care specialist consultation is associated with better quality of supportive care in three advanced cancers, predominantly driven by improvements in information and care planning. This study supports the effectiveness of early palliative care consultation in three common advanced cancers within the Veterans Affairs Health System and provides a greater understanding of what care processes palliative care teams influence.
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http://dx.doi.org/10.1016/j.jpainsymman.2016.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173291PMC
October 2016

The Symptom Experience in Rectal Cancer Survivors.

J Pain Symptom Manage 2016 11 30;52(5):709-718. Epub 2016 Sep 30.

Division of General Internal Medicine, University of California, Los Angeles, Los Angeles, California, USA; Anthem, Thousand Oaks, California, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.

Context: As the number of rectal cancer survivors grows, it is important to understand the symptom experience after treatment. Although data show that rectal cancer survivors experience a variety of symptoms after diagnosis, little has been done to study the way these symptoms are grouped and associated.

Objectives: To determine symptom prevalence and intensity in rectal cancer survivors and if clusters of survivors exist, who share similar symptom-defined survivor subgroups that may vary based on antecedent variables.

Methods: A secondary analysis of the Cancer Care and Outcomes Research and Surveillance database was undertaken. Cluster analysis was performed on 15-month postdiagnosis data to form post-treatment survivor subgroups, and these were examined for differences in demographic and clinical characteristics. Data were analyzed using cluster analysis, chi-square, and analysis of variance.

Results: A total of 275 rectal cancer survivors were included who had undergone chemotherapy, radiation therapy, and surgery. Most frequently reported symptoms included feeling "worn out" (87%), feeling "tired" (85%), and "trouble sleeping" (66%). Four symptom-defined survivor subgroups (minimally symptomatic n = 40, tired and trouble sleeping n = 138, moderate symptoms n = 42, and highly symptomatic n = 55) were identified with symptom differences existing among each subgroup. Age and being married/partnered were the only two antecedents found to differ across subgroups.

Conclusion: This study documents differences in the symptom experience after treatment. The identification of survivor subgroups allows researchers to further investigate tailored, supportive care strategies to minimize ongoing symptoms in those with the greatest symptom burden.
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http://dx.doi.org/10.1016/j.jpainsymman.2016.05.027DOI Listing
November 2016

Risk of Neutropenia-Related Hospitalization in Patients Who Received Colony-Stimulating Factors With Chemotherapy for Breast Cancer.

J Clin Oncol 2016 11 30;34(32):3872-3879. Epub 2016 Sep 30.

Abiy Agiro, Qinli Ma, Sze-jung Wu, and John J. Barron, HealthCore, Wilmington, DE; Anupama Kurup Acheson, Providence Cancer Center, Portland, OR; Debra A. Patt, Texas Oncology, Austin; Debra A. Patt, The US Oncology Network, Houston, TX; Jennifer L. Malin, Anthem, Woodland, CA; Alan Rosenberg, Anthem, Chicago, IL; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; and Gary H. Lyman, Hutchinson Institute for Cancer Outcomes Research and University of Washington, Seattle, WA.

Purpose To describe outcomes after granulocyte colony-stimulating factor (G-CSF) prophylaxis in patients with breast cancer who received chemotherapy regimens with low-to-intermediate risk of induction of neutropenia-related hospitalization. Patients and Methods We identified 8,745 patients age ≥ 18 years from a medical and pharmacy claims database for 14 commercial US health plans. This retrospective analysis included patients with breast cancer who began first-cycle chemotherapy from 2008 to 2013 using docetaxel and cyclophosphamide (TC); docetaxel, carboplatin, and trastuzumab (TCH); or doxorubicin and cyclophosphamide (conventional-dose AC) regimens. Primary prophylaxis (PP) was defined as G-CSF administration within 5 days of beginning chemotherapy. Outcome was neutropenia, fever, or infection-related hospitalization within 21 days of initiating chemotherapy. Multivariable regressions and number-needed-to-treat analyses were used. Results A total of 4,815 patients received TC (2,849 PP; 1,966 no PP); 2,292 patients received TCH (1,444 PP; 848 no PP); and 1,638 patients received AC (857 PP; 781 no PP) regimen. PP was associated with reduced risk of neutropenia-related hospitalization for TC (2.0% PP; 7.1% no PP; adjusted odds ratio [AOR], 0.29; 95% CI, 0.22 to 0.39) and TCH (1.3% PP; 7.1% no PP; AOR, 0.19; 95% CI, 0.12 to 0.30), but not AC (4.7% PP; 3.8% no PP; AOR, 1.21; 95% CI, 0.75 to 1.93) regimens. For the TC regimen, 20 patients (95% CI, 16 to 26) would have to be treated for 21 days to avoid one neutropenia-related hospitalization; with the TCH regimen, 18 patients (95% CI, 13 to 25) would have to be treated. Conclusion Primary G-CSF prophylaxis was associated with low-to-modest benefit in lowering neutropenia-related hospitalization in patients with breast cancer who received TC and TCH regimens. Further evaluation is needed to better understand which patients benefit most from G-CSF prophylaxis in this setting.
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http://dx.doi.org/10.1200/JCO.2016.67.2899DOI Listing
November 2016

Public Reporting of Hospital-Level Cancer Surgical Volumes in California: An Opportunity to Inform Decision Making and Improve Quality.

J Oncol Pract 2016 10;12(10):e944-e948

Cancer Prevention Institute of California, Fremont; Stanford University, Stanford; University of California, Pacific Business Group on Health, and Consumers Union of US, San Francisco; California Office of Statewide Health Planning and Development, and Covered California, Sacramento; Anthem, Woodland Hills; University of California, Los Angeles; California Health Care Foundation, Oakland; and Independent Health Policy Consultant, Berkeley, CA; Northwestern University, Chicago, IL; and Cynosure Health, Westford, MA.

Purpose: Most patients, providers, and payers make decisions about cancer hospitals without any objective data regarding quality or outcomes. We developed two online resources allowing users to search and compare timely data regarding hospital cancer surgery volumes.

Methods: Hospital cancer surgery volumes for all California hospitals were calculated using ICD-9 coded hospital discharge summary data. Cancer surgeries included (bladder, brain, breast, colon, esophagus, liver, lung, pancreas, prostate, rectum, and stomach) were selected on the basis of a rigorous literature review to confirm sufficient evidence of a positive association between volume and mortality. The literature could not identify threshold numbers of surgeries associated with better or worse outcomes. A multidisciplinary working group oversaw the project and ensured sound methodology.

Results: In California in 2014, about 60% of surgeries were performed at top-quintile-volume hospitals, but the per-hospital median numbers of surgeries for esophageal, pancreatic, stomach, liver, or bladder cancer surgeries were four or fewer. At least 670 patients received cancer surgery at hospitals that performed only one or two surgeries for a particular cancer type; 72% of those patients lived within 50 miles of a top-quintile-volume hospital.

Conclusion: There is clear potential for more readily available information about hospital volumes to help patient, providers, and payers choose cancer surgery hospitals. Our successful public reporting of hospital volumes in California represents an important first step toward making publicly available even more provider-specific data regarding cancer care quality, costs, and outcomes, so those data can inform decision-making and encourage quality improvement.
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http://dx.doi.org/10.1200/JOP.2016.010819DOI Listing
October 2016

Defining High-Quality Palliative Care in Oncology Practice: An American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine Guidance Statement.

J Oncol Pract 2016 09 16;12(9):e828-38. Epub 2016 Aug 16.

White River Junction VA Medical Center; Geisel School of Medicine at Dartmouth, White River Junction, VT; Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center, Boston, MA; Duke University Medical Center, Durham, NC; American Academy of Hospice and Palliative Medicine, Glenview, IL; Partnership for Health Analytic Research, Beverly Hills, CA; Mt Sinai Ichan School of Medicine, New York, NY; Providence Cancer Center, Portland, OR; Anthem, Indianapolis, IN; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; and Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: Integrated into routine oncology care, palliative care can improve symptom burden, quality of life, and patient and caregiver satisfaction. However, not all oncology practices have access to specialist palliative medicine. This project endeavored to define what constitutes high-quality primary palliative care as delivered by medical oncology practices.

Methods: An expert steering committee outlined 966 palliative care service items, in nine domains, each describing a candidate element of primary palliative care delivery for patients with advanced cancer or high symptom burden. Using modified Delphi methodology, 31 multidisciplinary panelists rated each service item on three constructs: importance, feasibility, and scope within medical oncology practice.

Results: Panelists endorsed the highest proportion of palliative care service items in the domains of End-of-Life Care (81%); Communication and Shared Decision Making (79%); and Advance Care Planning (78%). The lowest proportions were in Spiritual and Cultural Assessment and Management (35%) and Psychosocial Assessment and Management (39%). In the largest domain, Symptom Assessment and Management, there was consensus that all symptoms should be assessed and managed at a basic level, with more comprehensive management for common symptoms such as nausea, vomiting, diarrhea, dyspnea, and pain. Within the Appropriate Palliative Care and Hospice Referral domain, there was consensus that oncology practices should be able to describe the difference between palliative care and hospice to patients and refer patients appropriately.

Conclusion: This statement describes the elements comprising high-quality primary palliative care for patients with advanced cancer or high symptom burden, as delivered by oncology practices. Oncology providers wishing to enhance palliative care delivery may find this information useful to inform operational changes and quality improvement efforts.
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http://dx.doi.org/10.1200/JOP.2016.010686DOI Listing
September 2016

Transcriptional control of non-apoptotic developmental cell death in C. elegans.

Cell Death Differ 2016 12 29;23(12):1985-1994. Epub 2016 Jul 29.

Laboratory of Developmental Genetics, The Rockefeller University, New York, NY, USA.

Programmed cell death is an essential aspect of animal development. Mutations in vertebrate genes that mediate apoptosis only mildly perturb development, suggesting that other cell death modes likely have important roles. Linker cell-type death (LCD) is a morphologically conserved cell death form operating during the development of Caenorhabditis elegans and vertebrates. We recently described a molecular network governing LCD in C. elegans, delineating a key role for the transcription factor heat-shock factor 1 (HSF-1). Although HSF-1 functions to protect cells from stress in many settings by inducing expression of protein folding chaperones, it promotes LCD by inducing expression of the conserved E2 ubiquitin-conjugating enzyme LET-70/UBE2D2, which is not induced by stress. Following whole-genome RNA interference and candidate gene screens, we identified and characterized four conserved regulators required for LCD. Here we show that two of these, NOB-1/Hox and EOR-1/PLZF, act upstream of HSF-1, in the context of Wnt signaling. A third protein, NHR-67/TLX/NR2E1, also functions upstream of HSF-1, and has a separate activity that prevents precocious expression of HSF-1 transcriptional targets. We demonstrate that the SET-16/mixed lineage leukemia 3/4 (MLL3/4) chromatin regulation complex functions at the same step or downstream of HSF-1 to control LET-70/UBE2D2 expression. Our results identify conserved proteins governing LCD, and demonstrate that transcriptional regulators influence this process at multiple levels.
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http://dx.doi.org/10.1038/cdd.2016.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136488PMC
December 2016

Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status?

J Oncol Pract 2016 07 7;12(7):653-62. Epub 2016 Jun 7.

California State University Fullerton; Anthem, Woodland Hills; David Geffen School of Medicine, University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; National Cancer Institute, Bethesda, MD; Patient-Centered Outcomes Research Institute, Washington, DC; and University of Texas Medical Branch Health, Galveston, TX.

Purpose: Chemotherapy prolongs survival in patients with advanced non-small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists' recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations.

Methods: We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients' performance status and symptoms and physicians' demographic and practice characteristics with chemotherapy recommendations.

Results: Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P < .001). Compared with patient factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses.

Conclusion: Strong consensus among oncologists exists for chemotherapy in patients with advanced non-small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk-benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care.
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http://dx.doi.org/10.1200/JOP.2015.008425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957251PMC
July 2016

Lower Patient Ratings of Physician Communication Are Associated With Unmet Need for Symptom Management in Patients With Lung and Colorectal Cancer.

J Oncol Pract 2016 06 24;12(6):e654-69. Epub 2016 May 24.

David Geffen School of Medicine at University of California Los Angeles; Veterans Affairs Greater Los Angeles Healthcare System; UCLA Fielding School of Public Health, Los Angeles; RAND Corporation, Santa Monica; Kaiser Permanente Center for Effectiveness and Safety Research, Pasadena; California State University, Fullerton, CA; Brigham and Women's Hospital; Harvard Medical School; Dana-Farber Cancer Institute, Boston, MA; Johns Hopkins Kimmel Cancer Center, Baltimore, MD; Patient-Centered Outcomes Research Institute, Washington, DC.

Purpose: Little is known about factors associated with unmet needs for symptom management in patients with cancer.

Methods: Patients with a new diagnosis of lung and colorectal cancer from the diverse nationally representative Cancer Care Outcomes Research and Surveillance cohort completed a survey approximately 5 months after diagnosis (N = 5,422). We estimated the prevalence of unmet need for symptom management, defined as patients who report that they wanted help for at least one common symptom (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, diarrhea) during the 4 weeks before the survey but did not receive it. We identified patient factors associated with unmet need by using logistic regression with random effects to account for clustering within study sites.

Results: Overall, 15% (791 of 5,422) of patients had at least one unmet need for symptom management. Adjusting for sociodemographic and clinical factors, African American race, being uninsured or poor, having early-stage lung cancer, and the presence of moderate to severe symptoms were associated with unmet need (all P < .05). Furthermore, patients who rated their physician's communication score < 80 (on a 0 to 100 scale) had adjusted rates of an unmet need for symptom management that were more than twice as high as patients who rated their physicians with a perfect communication score (23.1% v 10.0%; P < .001).

Conclusion: A significant minority of patients with newly diagnosed lung and colorectal cancer report unmet needs for symptom management. Interventions to improve symptom management should consider the importance of physician communication to the patient's experience of disease.
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http://dx.doi.org/10.1200/JOP.2015.005538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957255PMC
June 2016

HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans.

Elife 2016 Mar 8;5. Epub 2016 Mar 8.

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States.

Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis. However, the details of LCD execution are not known. Here we delineate a molecular-genetic pathway governing LCD in C. elegans. Redundant activities of antagonistic Wnt signals, a temporal control pathway, and mitogen-activated protein kinase kinase signaling control heat shock factor 1 (HSF-1), a conserved stress-activated transcription factor. Rather than protecting cells, HSF-1 promotes their demise by activating components of the ubiquitin proteasome system, including the E2 ligase LET-70/UBE2D2 functioning with E3 components CUL-3, RBX-1, BTBD-2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.
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http://dx.doi.org/10.7554/eLife.12821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821803PMC
March 2016

Putting Cancer Care on the Right Path.

Manag Care 2015 Oct;24(10):48-9, 54-5

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October 2015

Cell Death in C. elegans Development.

Curr Top Dev Biol 2015 9;114:1-42. Epub 2015 Sep 9.

Laboratory of Developmental Genetics, The Rockefeller University, New York, USA. Electronic address:

Cell death is a common and important feature of animal development, and cell death defects underlie many human disease states. The nematode Caenorhabditis elegans has proven fertile ground for uncovering molecular and cellular processes controlling programmed cell death. A core pathway consisting of the conserved proteins EGL-1/BH3-only, CED-9/BCL2, CED-4/APAF1, and CED-3/caspase promotes most cell death in the nematode, and a conserved set of proteins ensures the engulfment and degradation of dying cells. Multiple regulatory pathways control cell death onset in C. elegans, and many reveal similarities with tumor formation pathways in mammals, supporting the idea that cell death plays key roles in malignant progression. Nonetheless, a number of observations suggest that our understanding of developmental cell death in C. elegans is incomplete. The interaction between dying and engulfing cells seems to be more complex than originally appreciated, and it appears that key aspects of cell death initiation are not fully understood. It has also become apparent that the conserved apoptotic pathway is dispensable for the demise of the C. elegans linker cell, leading to the discovery of a previously unexplored gene program promoting cell death. Here, we review studies that formed the foundation of cell death research in C. elegans and describe new observations that expand, and in some cases remodel, this edifice. We raise the possibility that, in some cells, more than one death program may be needed to ensure cell death fidelity.
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http://dx.doi.org/10.1016/bs.ctdb.2015.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206663PMC
July 2016

Complications Associated With Use of Long-Term Central Venous Catheters Among Commercially Insured Women With Breast Cancer.

J Oncol Pract 2015 Nov 11;11(6):505-10. Epub 2015 Aug 11.

Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, NY; HealthCore, Wilmington DE; and Anthem, Indianapolis, IN.

Purpose: Despite some advantages to their use, long-term central venous catheters (CVCs) are associated with complications for patients who require chemotherapy. Understanding of these risks in commercially insured populations is limited. This information can inform medical policies that ensure the appropriate use of venous access devices. This study's objectives were to assess the extent of variation in use of long-term CVCs in a cohort of commercially insured women with breast cancer, and to assess risks of associated complications.

Methods: Retrospective cohort analysis was conducted using health insurance claims between January 2006 and October 2013. The cohort included commercially insured women age ≥ 18 years diagnosed with breast cancer who received infusion chemotherapy (N = 31,047). We conducted matched and case-mix adjusted Cox proportional hazard modeling to assess differences in bloodstream infections and thrombovascular complications between patients using long-term CVCs and those using temporary intravenous catheters.

Results: Approximately two thirds of the cohort had a long-term CVC, although rates varied across regions (57% to 75%), health plans (65% to 70%), and insurance coverage (63% to 68%). After propensity score matching, the adjusted hazard ratio for infection was 2.70 (95% CI, 2.31 to 3.16) and thrombovascular complications, 2.61 (95% CI, 2.33 to 2.93) in patients with long-term CVCs compared with those with temporary intravenous catheters.

Conclusion: Although long-term CVCs may have benefits, they are associated with increased morbidity. Regional and health plan variation in long-term CVC insertion suggests that some of their use reflects provider- or institution-driven variation in practice. Evidence-based guidelines and tools may help decrease discretionary use of long-term CVCs.
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http://dx.doi.org/10.1200/JOP.2015.004796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647067PMC
November 2015

NCCN Roundtable:Value-Based Decision-Making at the Bedside.

J Natl Compr Canc Netw 2015 May;13(5 Suppl):659-61

As part of the NCCN 20th Annual Conference: Advancing the Standard of Cancer Care, a distinguished and diverse group of experts on value-based decision-making in oncology discussed guidelines and pathways and how their use has impacted bedside evidence-based decision-making for both physicians and patients. Moderated by Clifford Goodman, PhD, the roundtable also reflected on the criteria used to assess shared decision-making and the relationship between outcomes and cost when determining value.
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http://dx.doi.org/10.6004/jnccn.2015.0196DOI Listing
May 2015

NCCN Roundtable: What Are the Characteristics of an Optimal Clinical Practice Guideline?

J Natl Compr Canc Netw 2015 May;13(5 Suppl):640-2

Much has changed in the treatment of cancer since the first NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) were rolled out for 8 different tumor types in November 1996. NCCN Guidelines now include involved algorithms often containing multiple treatment alternatives and detailed pathways of care that depend on more-specific patient characteristics and molecular tumor diagnostics. With 47 different individual NCCN panels, all members of the cancer care team are now better informed than ever to guide patients through the often complex decision-making required to improve the odds of successful outcomes. At the NCCN 20th Annual Conference, a distinguished panel assembled to take a closer look at these invaluable clinical practice guidelines, first glancing backward to how it all started and then forward to explore the key ingredients of trustworthy guidelines.
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http://dx.doi.org/10.6004/jnccn.2015.0190DOI Listing
May 2015

Quality of supportive care for patients with advanced lung cancer in the Veterans Health Administration.

J Community Support Oncol 2014 Oct;12(10):361-9

Veterans Administration Greater Los Angeles Healthcare System, West Los Angeles, Los Angeles, California, USA; and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.

Background: Morbidity related to cancer and its treatment remains a significant source of human suffering and a challenge to the delivery of high-quality care.

Objectives: To develop and apply quality indicators to evaluate quality of supportive care for advanced lung cancer in the Veterans Health Administration (VHA) and examine facility-level predictors of quality.

Methods: We evaluated supportive care quality using 12 quality indicators. Data were taken from VHA electronic health records for incident lung cancer cases occurring during 2007. Organizational characteristics of 111 VHA facilities were examined for association with receipt of care.

Limitations: Not all supportive care was evaluated. Care processes identified as present at facilities may not have been applied to cohort patients. Facility-level results may be influenced by errors in attributing a patient's care to the correct facility.

Conclusions: Quality indicators for supportive cancer care can be developed and applied in large evaluations using electronic health record review. This study confirmed high-quality supportive care, while identifying significant facility-level variation in VHA.
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http://dx.doi.org/10.12788/jcso.0079DOI Listing
October 2014

Hypofractionated whole breast irradiation for early-stage breast cancer--reply.

JAMA 2015 Apr;313(13):1371

Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia.

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http://dx.doi.org/10.1001/jama.2015.1644DOI Listing
April 2015
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