Publications by authors named "Neal J Meropol"

214 Publications

The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials.

J Geriatr Oncol 2021 Oct 27. Epub 2021 Oct 27.

Memorial Sloan Kettering Cancer Center, USA.

Purpose: Expected toxicity from chemoradiation (CRT) is an important factor in treatment decisions but is poorly understood in older adults with lower gastrointestinal (GI) malignancies. Our objective was to compare acute adverse events (AAEs) of older and younger adults with lower GI malignancies treated on NRG studies.

Methods: Data from 6 NRG trials, testing combined modality therapy in patients with anal or rectal cancer, were used to test the hypothesis that older age was associated with increased AAEs. AAEs and compliance with protocol-directed therapy were compared between patients aged ≥70 and < 70. Categorical variables were compared across age groups using the chi-square test. The association of age on AAEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value <0.01 was considered statistically significant.

Results: There were 2525 patients, including 380 patients ≥70 years old (15%) evaluable. Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p = 0.001), but otherwise baseline characteristics were similar. Older patients were less likely to complete their chemotherapy (78% vs. 87%, p < 0.001), but had similar RT duration. On univariate analysis, older patients were more likely to experience grade ≥ 3 GI AAEs (36% vs. 23%, p < 0.001), and less likely to experience grade ≥ 3 skin AAEs (8% vs. 14%, p = 0.002). On multivariable analysis, older age was associated with grade ≥ 3 GI AAE (OR 1.93, 95% CI: 1.52, 2.47, p < 0.001) after adjusting for sex, race, PS, and disease site.

Conclusions: Older patients with lower GI cancers who underwent CRT were less likely to complete chemotherapy and had higher rates of grade 3+ GI AAEs. These results can be used to counsel older adults prior to treatment and manage expected toxicities throughout pelvic CRT.
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http://dx.doi.org/10.1016/j.jgo.2021.10.008DOI Listing
October 2021

Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in + NSCLC.

J Comp Eff Res 2021 Dec 24;10(17):1271-1282. Epub 2021 Aug 24.

F. Hoffmann-La Roche Ltd, Hexagon Place, Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, UK.

Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Entrectinib-treated adults with advanced fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65). Primary end point, time-to-treatment discontinuation (TTD); secondary end points, PFS and OS. Median (95% CI) weighted TTD: 12.9 (9.9-17.4) months for entrectinib; 8.8 (6.2-9.9) months for crizotinib (weighted hazard ratio: 0.72 [0.51-1.02]). Median OS with entrectinib was not reached, weighted median OS with crizotinib was 18.5 (15.1-19.9) months. Entrectinib administered in clinical trials may be associated with longer TTD than a real-world crizotinib population.
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http://dx.doi.org/10.2217/cer-2021-0131DOI Listing
December 2021

ACA Medicaid expansion association with racial disparity reductions in timely cancer treatment.

Am J Manag Care 2021 07;27(7):274-281

Flatiron Health, Inc, 233 Spring St, Fifth Fl, New York, NY 10025. Email:

Objectives: Racial disparities in cancer care and outcomes remain a societal challenge. Medicaid expansion through the Affordable Care Act was intended to improve health care access and equity. This study aimed to assess whether state Medicaid expansions were associated with a reduction in racial disparities in timely treatment among patients diagnosed with advanced cancer.

Study Design: This difference-in-differences study analyzed deidentified electronic health record-derived data. Patients aged 18 to 64 years with advanced or metastatic cancers diagnosed between January 1, 2011, and January 31, 2019, and receiving systemic therapy were included.

Methods: The primary end point was receipt of timely treatment, defined as first-line systemic therapy starting within 30 days after diagnosis of advanced or metastatic disease. Racial disparity was defined as adjusted percentage-point (PP) difference for Black vs White patients, adjusted for age, sex, practice setting, cancer type, stage, insurance marketplace, and area unemployment rate, with time and state fixed effects.

Results: The study included 30,310 patients (12.3% Black race). Without Medicaid expansion, Black patients were less likely to receive timely treatment than White patients (43.7% vs 48.4%; adjusted difference, -4.8 PP; P < .001). With Medicaid expansion, this disparity was diminished and lost significance (49.7% vs 50.5%; adjusted difference, -0.8 PP; P = .605). The adjusted difference-in-differences estimate was a 3.9 PP reduction in racial disparity (95% CI, 0.1-7.7 PP; P = .045).

Conclusions: Medicaid expansion was associated with reduced Black-White racial disparities in receipt of timely systemic treatment for patients with advanced or metastatic cancers.
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http://dx.doi.org/10.37765/ajmc.2021.88700DOI Listing
July 2021

A Grant-Based Experiment to Train Clinical Investigators: The AACR/ASCO Methods in Clinical Cancer Research Workshop.

Clin Cancer Res 2021 Oct 26;27(20):5472-5481. Epub 2021 Jul 26.

University of Geneva Faculty of Medicine, Geneva, Switzerland.

To address the need for clinical investigators in oncology, American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) established the Methods in Clinical Cancer Research Workshop (MCCRW). The workshop's objectives were to: (i) provide training in the methods, design, and conduct of clinical trials; (ii) ensure that clinical trials met federal and international ethical guidelines; (iii) evaluate the effectiveness of the workshop; and (iv) create networking opportunities for young investigators with mentoring senior faculty. Educational methods included: (i) didactic lectures, (ii) Small Group Discussion Sessions, (iii) Protocol Development Groups, and (iv) one-on-one mentoring. Learning focused on the development of an Institutional Review Board (IRB)-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (i) pre- and postworkshop tests, (ii) students' workshop evaluations, (iii) faculty's ratings of protocol development, (iv) students' productivity in clinical research after the workshop, and (v) an independent assessment of the workshop. From 1996 to 2014, 1,932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the postworkshop exams ( < 0.001). Across the classes, student evaluations were very favorable. At the end of the workshop, faculty rated 92% to 100% of the students' protocols as ready for IRB submission. Intermediate and long-term follow-ups indicated that more than 92% of students were actively involved in patient-related research, and 66% had implemented five or more protocols. This NCI-sponsored MCCRW has had a major impact on the training of clinicians in their ability to design and implement clinical trials in cancer research.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530870PMC
October 2021

A pilot study of a low glycemic load diet in patients with stage I-III colorectal cancer.

J Gastrointest Oncol 2021 Jun;12(3):910-920

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Background: Consumption of a diet with high glycemic indices has been associated with inferior cancer-specific outcomes in patients with early-stage colorectal cancer, but there is limited prospective evidence that alterations in dietary habits improves cancer outcomes. This study aimed to determine the feasibility and acceptability of following a low glycemic load (GL) diet in patients with stage I-III colorectal cancer.

Methods: Patients with stage I-III colorectal cancer, who completed definitive therapy, and consumed an average daily GL >150 participated in a 12-week tailored face-to-face dietary intervention with a target GL. This study followed a 2-stage design, with 4 planned cohorts, each with an assigned GL target and dietary intervention intensity. The primary endpoint of feasibility was determined by participant compliance, defined as an individual following the assigned GL ≥75% of the time. Compliance was determined using 24-hour telephone recalls. A cohort was deemed feasible if at least 67% of participants were compliant. Secondary endpoints included acceptability of the diet, nutritional support resources necessary to follow the diet, and evaluation of the effect of the diet on physical measures and correlative laboratories.

Results: Only cohort 1 was required as the primary endpoint of feasibility was met (stringent GL target, low intensity dietary support). The majority of participants experienced a decrease in body mass index (BMI) and waist circumference, 29% experiencing meaningful weight loss (≥5%). The dietitian spent an average of 6.97 hours (SD 2.18) face-to-face time and 1.58 hours (SD 0.68) by phone with each participant. Significant decreases were seen in total cholesterol, very-low-density lipoprotein (VLDL) and triglycerides (all P<0.05). All participants liked the foods and were satisfied with the diet. All participants felt the in-person meetings were helpful, and 62% did not feel a virtual meeting (e.g., Skype, etc.) could replace in-person meetings.

Conclusions: Patients with stage I-III colorectal cancer can follow a low GL diet with a 12-week in-person dietary intervention. Significant changes in physical and laboratory measures suggest relevant biologic effects of the dietary intervention. This study establishes feasibility, and warrants a larger scale prospective intervention trial to evaluate the impact of a low GL diet on cancer outcomes.
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http://dx.doi.org/10.21037/jgo-20-330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261320PMC
June 2021

Progress in the Application of Machine Learning Algorithms to Cancer Research and Care.

JAMA Netw Open 2021 Jul 1;4(7):e2116063. Epub 2021 Jul 1.

Flatiron Health, New York, New York.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.16063DOI Listing
July 2021

Randomized trial of a web-based nurse education intervention to increase discussion of clinical trials.

Contemp Clin Trials Commun 2021 Jun 4;22:100789. Epub 2021 Jun 4.

Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.

Background: Clinical trials are a critical source of evidence for oncology care, yet very few patients participate. Among healthcare providers, nurses spend the most time with cancer patients and are the most highly trusted professionals. We developed and evaluated an educational program for oncology nurses targeting knowledge, attitudes, self-efficacy and perceived norms to facilitate discussion about clinical trials and support patient decision making.

Methods: A nationwide sample of oncology nurses were randomly assigned to receive general clinical trials education delivered as text (attention control) vs. tailored video vignettes (intervention) in a web-based continuing education program. Participants completed a baseline assessment and follow up assessments immediately after the educational program and three months later. The primary outcome was intention to discuss clinical trials with patients. Secondary outcomes were knowledge and attitudes about clinical trials, self-efficacy, and perceived norms.

Results: 1393 nurses enrolled and completed the educational program and post-intervention assessment (720 control, 673 video). Both text education and tailored video education increased intention to discuss clinical trials with patients, with a greater effect in the video group (p < .0001). Likewise, knowledge, attitudes, perceived behavioral control, and perceived norms were all improved with education in both groups, and the magnitude of benefit was greater (p < .001) for the video group in all outcomes except knowledge.

Conclusion: A one-time online educational program for oncology nurses improves knowledge, attitudes, self-efficacy and intention to engage patients in discussions about clinical trials. A tailored video format was associated with a greater effect than standard text only material.
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http://dx.doi.org/10.1016/j.conctc.2021.100789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209078PMC
June 2021

A randomized controlled trial of structured palliative care versus standard supportive care for patients enrolled in phase 1 clinical trials.

Cancer Med 2021 07 25;10(13):4312-4321. Epub 2021 May 25.

Department of Medicine, University Hospitals Cleveland Medical Center, Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, USA.

Purpose: Patients enrolled in Phase 1 clinical trials have typically exhausted standard therapies and often are choosing between a clinical trial and hospice care. Significant symptom burden can result in early trial discontinuation and confound trial outcomes. This study aimed to examine differences in study duration, symptom burden, adverse events (AE), and quality of life (QOL) between those receiving structured palliative care versus usual supportive care.

Patients And Methods: Sixty-eight patients enrolled in phase 1 clinical trials and 39 of their CGs were randomly assigned to receive structured palliative care or usual supportive care. Patient QOL was measured monthly using the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale. The Quality of Life in Life-Threatening Illness-Family Care Version and Caregiver Reaction Assessment were used for CGs. AEs and use of palliative care resources were compared between arms.

Results: Mean duration of the phase 1 study was 142 days in the palliative care arm versus 116 days in the usual care arm (p = 0.55). Although not statistically significant, patients in the palliative care arm experienced fewer AEs and better QOL, as did their CGs, compared to those receiving usual care.

Conclusions: Phase 1 patients and their CGs have physical and psychosocial needs warranting palliative care services. Results suggest that structured palliative care is associated with the increased duration of the study and improved patient and CG QOL.
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http://dx.doi.org/10.1002/cam4.3971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267138PMC
July 2021

Adherence to and determinants of guideline-recommended biomarker testing and targeted therapy in patients with gastroesophageal adenocarcinoma: Insights from routine practice.

Cancer 2021 Jul 17;127(14):2562-2570. Epub 2021 Mar 17.

Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Anti human epidermal growth factor receptor 2 (anti-HER2) therapy with trastuzumab improves overall survival in patients with advanced, HER2-positive gastroesophageal adenocarcinoma (GEA) and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine practice.

Methods: The authors performed a cross-sectional study of patients who had advanced GEA diagnosed between January 2011 and June 2019 in a nationwide electronic health record-derived database. The annual prevalences of both timely HER2 testing (defined within 21 days after advanced diagnosis) and timely trastuzumab initiation (defined within 14 days after a positive HER2 result) were calculated. Log-binomial regressions estimated adjusted prevalence ratios comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics.

Results: In total, the cohort included 6032 patients with advanced GEA of whom 1007 were HER2-positive. Between 2011 and 2019, timely HER2 testing increased from 22.4% to 44.5%, whereas timely trastuzumab initiation remained stable at 16.3%. No appreciable differences in timely testing or trastuzumab initiation were noted by age, sex, race, or insurance status. Compared with patients who had metastatic disease at diagnosis, patients who had early stage GEA who did not undergo surgery were less likely to receive timely HER2 testing and trastuzumab initiation (testing prevalence ratio, 0.69; 95% CI, 0.64-0.75; treatment prevalence ratio, 0.32; 95% CI, 0.18-0.56), as were patients with early stage disease who subsequently developed a distant recurrence (testing prevalence ratio, 0.56; 95% CI, 0.47-0.65; treatment prevalence ratio, 0.61; 95% CI, 0.24-1.55).

Conclusions: In patients with advanced GEA, guideline-recommended HER2 testing and anti-HER2 therapy remain underused. Uptake may improve with universal HER2 testing regardless of stage.
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http://dx.doi.org/10.1002/cncr.33514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249344PMC
July 2021

Using electronic health record data to identify comparator populations for comparative effectiveness research.

J Med Econ 2020 Dec 10;23(12):1618-1622. Epub 2020 Nov 10.

Flatiron Health, Inc, New York, NY, USA.

Electronic health records (EHRs) can define real world patient populations with high levels of clinical specificity, potentially addressing some of the shortcomings of other types of real world data (RWD) when informing decisions about the comparative effectiveness of medical technologies. An important but under-recognized concern for EHR-derived RWD, however, is that the rich clinical data permits creation of very homogenous subpopulations from the larger group of eligible patients, thereby reducing the representativeness of the cohort relative to clinical practice. In this article, we discuss the tradeoffs between choosing clinical specificity versus representativeness in population sampling for comparative effectiveness research. Using EHR-derived RWD, we provide an example in non-small cell lung cancer to illustrate the concepts, showing wide variation in outcomes among potential comparator cohorts. We close with several recommendations for selecting comparator populations from EHRs that address the balance between matching clinical guidelines and capturing practice variability in comparative effectiveness research.
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http://dx.doi.org/10.1080/13696998.2020.1840113DOI Listing
December 2020

5-Fluorouracil Enhances the Antitumor Activity of the Glutaminase Inhibitor CB-839 against -Mutant Colorectal Cancers.

Cancer Res 2020 11 9;80(21):4815-4827. Epub 2020 Sep 9.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.

encodes the p110α catalytic subunit of PI3K and is frequently mutated in human cancers, including ∼30% of colorectal cancer. Oncogenic mutations in render colorectal cancers more dependent on glutamine. Here we report that the glutaminase inhibitor CB-839 preferentially inhibits xenograft growth of -mutant, but not wild-type (WT), colorectal cancers. Moreover, the combination of CB-839 and 5-fluorouracil (5-FU) induces -mutant tumor regression in xenograft models. CB-839 treatment increased reactive oxygen species and caused nuclear translocation of Nrf2, which in turn upregulated mRNA expression of uridine phosphorylase 1 (UPP1). UPP1 facilitated the conversion of 5-FU to its active compound, thereby enhancing the inhibition of thymidylate synthase. Consistently, knockout of UPP1 abrogated the tumor inhibitory effect of combined CB-839 and 5-FU administration. A phase I clinical trial showed that the combination of CB-839 and capecitabine, a prodrug of 5-FU, was well tolerated at biologically-active doses. Although not designed to test efficacy, an exploratory analysis of the phase I data showed a trend that -mutant patients with colorectal cancer might derive greater benefit from this treatment strategy as compared with WT patients with colorectal cancer. These results effectively demonstrate that targeting glutamine metabolism may be an effective approach for treating patients with -mutant colorectal cancers and warrants further clinical evaluation. SIGNIFICANCE: Preclinical and clinical trial data suggest that the combination of CB-839 with capecitabine could serve as an effective treatment for -mutant colorectal cancers.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642187PMC
November 2020

Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors.

Invest New Drugs 2021 02 17;39(1):142-151. Epub 2020 Jun 17.

Case Comprehensive Cancer Center, Case Western Reserve University, University Hospitals Seidman Cancer Center, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH, 44106, USA.

Temozolomide (TMZ) generates DNA adducts that are repaired by direct DNA and base excision repair mechanisms. Methoxyamine (MX, TRC-102) potentiates TMZ activity by binding to apurinic and apyrimidinic (AP) sites after removal of N-methyladenine and N-methylguanine, inhibiting site recognition of AP endonuclease. We conducted a phase I trial to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of intravenous MX when given with oral TMZ. Patients with advanced solid tumors and progression on standard treatment were enrolled to a standard 3 + 3 dose escalation trial assessing escalating doses of TMZ and MX. Tumor response was assessed per RECIST and adverse events (AEs) by CTCAEv3. Pharmacokinetics (PK) of MX and COMET assays on peripheral blood mononuclear cells were performed. 38 patients were enrolled-median age 59.5 years (38-76), mean number of cycles 2.9 [1-13]. No DLTs were observed. Cycle 1 grade 3 AEs included fatigue, lymphopenia, anemia, INR, leukopenia, neutropenia, allergic reaction, constipation, psychosis and paranoia. Cycle 2-13 grade 4 AEs included thrombocytopenia and confusion. A partial response was seen in 1 patient with a pancreatic neuroendocrine tumor (PNET) and six additional patients, each with different tumor types, demonstrated prolonged stable disease. MX PK was linear with dose and was not affected by concomitant TMZ. TMZ 200 mg/m daily × 5 may be safely administered with MX 150 mg/m intravenously once on day 1 with minimal toxicity. Further studies assessing this drug combination in select tumor types where temozolomide has activity may be warranted.
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http://dx.doi.org/10.1007/s10637-020-00962-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744386PMC
February 2021

Evaluating the Impact of Oncology Care Model Reporting Requirements on Biomarker Testing and Treatment.

JCO Oncol Pract 2020 10 4;16(10):e1216-e1221. Epub 2020 Jun 4.

Flatiron Health, New York, NY.

Purpose: The Oncology Care Model (OCM) is Medicare's first alternative payment model program for patients with cancer. As of October 2017, participating practices were required to report biomarker testing of patients with advanced non-small-cell lung cancer (aNSCLC). Our objective was to evaluate the effect of this OCM reporting requirement on quality of care.

Methods: We selected patients with aNSCLC receiving care in practices in a nationwide de-identified electronic health record-derived database. We used an adjusted difference-in-differences (DID) logistic regression model to compare changes in biomarker testing rates (EGFR, ROS1, and ALK) and receipt of biomarker-guided therapy between patients in OCM versus non-OCM practices, before and after OCM implementation.

Results: The analysis included 14,048 patients from 45 OCM practices (n = 8,151) and 105 non-OCM practices (n = 5,897). The overall unadjusted rates for biomarker testing and receipt of biomarker-guided therapy increased over the study period (2011-2018) in both OCM (55.5% 71.6%; 89.8% 94.6%, respectively) and non-OCM (55.2% 69.7%; 90.1% 95.2%, respectively) practices. In the adjusted DID model, the rates of biomarker testing (odds ratio [OR], 1.09 [95% CI, 0.88 to 1.34]; = .45) and receipt of biomarker-guided therapy (OR, 0.87 [95% CI, 0.52 to 1.45]; = .58) were similar between OCM and non-OCM practices.

Conclusion: OCM biomarker documentation and reporting requirements did not appear to increase the proportions of patients with aNSCLC who underwent testing or who received biomarker-guided therapy in OCM versus non-OCM practices.
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http://dx.doi.org/10.1200/JOP.19.00747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564129PMC
October 2020

Quality Measurement in Cancer Care: A Review and Endorsement of High-Impact Measures and Concepts.

J Natl Compr Canc Netw 2020 03;18(3):250-259

National Comprehensive Cancer Network, Plymouth Meeting, Pennsylvania.

Although oncology care has evolved, outcome assessment remains a key challenge. Outcome measurement requires identification and adoption of a succinct list of metrics indicative of high-quality cancer care for use within and across healthcare systems. NCCN established an advisory committee, the NCCN Quality and Outcomes Committee, consisting of provider experts from NCCN Member Institutions and other stakeholders, including payers and patient advocacy, community oncology, and health information technology representatives, to review the existing quality landscape and identify contemporary, relevant cancer quality and outcomes measures by reevaluating validated measures for endorsement and proposing new measure concepts to fill crucial gaps. This manuscript reports on 22 measures and concepts; 15 that align with existing measures and 7 that are new.
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http://dx.doi.org/10.6004/jnccn.2020.7536DOI Listing
March 2020

Prognostic Significance of Patient-Reported Outcomes in Cancer.

JCO Oncol Pract 2020 04 9;16(4):e313-e323. Epub 2020 Jan 9.

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

Purpose: Performance status (PS), an established prognostic surrogate of cancer survival, is a physician-synthesized metric of patient symptoms and mobility that is prone to bias and subjectivity. The National Cancer Institute (NCI) Patient-Reported Outcomes Measurement Information System-Cancer (PROMIS-Ca) Bank, a patient-centric patient-reported outcome (PRO) evaluation of physical function (PF), fatigue, depression, anxiety, and pain, shares subject matter with PS and, therefore, may also be prognostic while eliminating physician interpretation.

Methods: Patients at Huntsman Cancer Institute were assessed using the NCI PROMIS-Ca Bank. Using tablets at routine office visits, PF, fatigue, depression, anxiety, and pain scores were collected from patients with advanced melanoma, non-small-cell lung cancer, colorectal cancer, and breast cancer. A PRO score collected at a single time point within 6 months of metastatic diagnosis for each patient was merged with curated clinical outcome data. The association of PROs, overall survival (OS), and hospitalization-free survival (HFS) were assessed in multivariable analysis that included sex and cancer type.

Results: Two hundred eighty-two complete sets of patient data were available for analysis. All 5 PRO domains were strongly prognostic of OS and HFS. While the PRO domains were interrelated with moderate to strong correlations (0.40-0.79), multivariable regression suggested that PF was most strongly associated with the clinical outcomes of OS ( < .001) and HFS ( < .001).

Conclusion: NCI PROMIS-Ca PROs may be prognostic of both cancer survival and likelihood of hospitalization. Future prospective studies are needed for all major prognostic factors to fully understand the independent prognostic value of PROs.
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http://dx.doi.org/10.1200/JOP.19.00329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846047PMC
April 2020

Developing and Sustaining an Effective and Resilient Oncology Careforce: Opportunities for Action.

J Natl Cancer Inst 2020 07;112(7):663-670

Division of Hematology & Oncology, Perelman School of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Advances in cancer care have led to improved survival, which, coupled with demographic trends, have contributed to rapid growth in the number of patients needing cancer care services. However, with increasing caseload, care complexity, and administrative burden, the current workforce is ill equipped to meet these burgeoning new demands. These trends have contributed to clinician burnout, compounding a widening workforce shortage. Moreover, family caregivers, who have unique knowledge of patient preferences, symptoms, and goals of care, are infrequently appreciated and supported as integral members of the oncology "careforce." A crisis is looming, which will hinder access to timely, high-quality cancer care if left unchecked. Stemming from the proceedings of a 2019 workshop convened by the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine, this commentary characterizes the factors contributing to an increasingly strained oncology careforce and presents multilevel strategies to improve its efficiency, effectiveness, and resilience. Together, these will enable today's oncology careforce to provide high-quality care to more patients while improving the patient, caregiver, and clinician experience.
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http://dx.doi.org/10.1093/jnci/djz239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357321PMC
July 2020

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).

Oncologist 2020 05 18;25(5):e798-e807. Epub 2019 Dec 18.

Northwestern University, Chicago, Illinois, USA.

Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum.

Subjects, Materials, And Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles.

Results: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue.

Conclusion: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer.

Implications For Practice: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.
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http://dx.doi.org/10.1634/theoncologist.2019-0437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216434PMC
May 2020

First-line immune checkpoint inhibitor use in cisplatin-eligible patients with advanced urothelial carcinoma: a secular trend analysis.

Future Oncol 2020 Jan 16;16(2):4341-4345. Epub 2019 Dec 16.

Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

 Standard first-line treatment of advanced urothelial cell carcinoma involves cisplatin-based chemotherapy, with carboplatin or immune checkpoint inhibitor therapy (ICI) reserved for cisplatin-ineligible individuals. Using a large de-identified electronic health record-derived database of patients with advanced urothelial cell carcinoma in the USA, we examined trends in utilization of first-line systemic therapies in cisplatin-eligible patients from 1 January 2015 to 31 March 2018. Among 1181 cisplatin-eligible patients, the quarterly proportion who received first-line ICI increased from 1 to 42% (p <0.001), while the proportion who received cisplatin-based chemotherapy decreased from 53 to 33% (p = 0.018). Patients receiving ICI were older than those receiving cisplatin (median age: 75 vs 68). Our analysis suggests rising off-label ICI use in cisplatin-eligible individuals, potentially because of ICI's favorable toxicity profile.
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http://dx.doi.org/10.2217/fon-2019-0578DOI Listing
January 2020

Recruitment Strategies for Nurse Enrollment in an Online Study.

Nurs Res 2020 Jan/Feb;69(1):69-73

Jessica Surdam, MPH, is Research Project Director, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio. Barbara Daly, PhD, RN, FAAN, is Professor, School of Medicine, Case Western Reserve University, Cleveland, Ohio. Sarah Fulton, MA, is Research Operations Manager, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio. Seunghee Margevicius, PhD, is Research Associate, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio. Mark Schluchter, PhD, is Professor, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio. Susan Flocke, PhD, is Professor of Family Medicine, School of Medicine, Oregon Health & Science University, Portland, Ohio. Sharon Manne, PhD, is Professor, Robert Wood Johnson Medical School, Rutgers, State University of New Jersey, New Brunswick. Neal J. Meropol, MD, is Vice President, Research Oncology, Flatiron Health, New York, New York, and Adjunct Professor, Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio.

Background: Although there is a great deal of literature regarding effective recruitment and challenges of recruiting specific patient populations, there is less known about best practices for recruitment of nurses as study subjects.

Objectives: The purpose of this article is to report our experience with recruitment and retention for a randomized trial of an online educational program to prepare oncology nurses to discuss oncology clinical trials with patients.

Methods: The study population included currently employed oncology nurses with direct patient interaction. There were three phases of this study: (1) qualitative interviews, (2) a pilot test, and (3) the randomized trial. Phase 3 was rolled out in five waves of recruitment. The distinct phases of the study-and the gradual roll out of recruitment during Phase 3-allowed us to test and refine our recruitment and retention methods for the randomized trial. Upon analysis of our response rate and attrition after the first wave of recruitment in Phase 3, we made several changes to improve recruitment and retention, including adding incentives, shortening the survey, and increasing the number of reminders to complete the program.

Results: The response rate was higher when we used both e-mail and U.S. postal mail solicitations. After the first wave of recruitment in the final phase, changes in our strategies did not increase our overall response rate significantly; however, the rate of attrition following baseline declined.

Discussion: Recruitment planning is an important component of successful clinical research. The use of the Internet for both recruitment of subjects and testing of interventions remains a cost-effective and potentially high yield methodology. Our research demonstrated several successful approaches to yield increased participation and retention of subjects, including seeking formal relationships with professional organizations as sponsors or supporters, providing meaningful incentives to participants, keeping surveys or questionnaires as short as possible, and planning multiple follow-up contacts from the outset.
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http://dx.doi.org/10.1097/NNR.0000000000000393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911026PMC
April 2020

Validation of diagnosis codes to identify side of colon in an electronic health record registry.

BMC Med Res Methodol 2019 08 19;19(1):177. Epub 2019 Aug 19.

Flatiron Health, New York, NY, USA.

Background: The use of real-world data to generate evidence requires careful assessment and validation of critical variables before drawing clinical conclusions. Prospective clinical trial data suggest that anatomic origin of colon cancer impacts prognosis and treatment effectiveness. As an initial step in validating this observation in routine clinical settings, we explored the feasibility and accuracy of obtaining information on tumor sidedness from electronic health records (EHR) billing codes.

Methods: Nine thousand four hundred three patients with metastatic colorectal cancer (mCRC) were selected from the Flatiron Health database, which is derived from de-identified EHR data. This study included a random sample of 200 mCRC patients. Tumor site data derived from International Classification of Diseases (ICD) codes were compared with data abstracted from unstructured documents in the EHR (e.g. surgical and pathology notes). Concordance was determined via observed agreement and Cohen's kappa coefficient (κ). Accuracy of ICD codes for each tumor site (left, right, transverse) was determined by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and corresponding 95% confidence intervals, using abstracted data as the gold standard.

Results: Study patients had similar characteristics and side of colon distribution compared with the full mCRC dataset. The observed agreement between the ICD codes and abstracted data for tumor site for all sampled patients was 0.58 (κ = 0.41). When restricting to the 62% of patients with a side-specific ICD code, the observed agreement was 0.84 (κ = 0.79). The specificity (92-98%) of structured data for tumor location was high, with lower sensitivity (49-63%), PPV (64-92%) and NPV (72-97%). Demographic and clinical characteristics were similar between patients with specific and non-specific side of colon ICD codes.

Conclusions: ICD codes are a highly reliable indicator of tumor location when the specific location code is entered in the EHR. However, non-specific side of colon ICD codes are present for a sizable minority of patients, and structured data alone may not be adequate to support testing of some research hypotheses. Careful assessment of key variables is required before determining the need for clinical abstraction to supplement structured data in generating real-world evidence from EHRs.
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http://dx.doi.org/10.1186/s12874-019-0824-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700780PMC
August 2019

Effectiveness of First-line Immune Checkpoint Blockade Versus Carboplatin-based Chemotherapy for Metastatic Urothelial Cancer.

Eur Urol 2019 10 28;76(4):524-532. Epub 2019 Jul 28.

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Background: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown.

Objective: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy.

Design, Setting, And Participants: We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database.

Outcome Measurements And Statistical Analysis: The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness.

Results And Limitations: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0-45.3%] vs 46.1% [95% CI 43.4-48.8%]) but higher at 36 mo (28.3% [95% CI 21.8-34.7%] vs 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding.

Conclusions: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy.

Patient Summary: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.
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http://dx.doi.org/10.1016/j.eururo.2019.07.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822167PMC
October 2019

Cost Effectiveness of Multigene Panel Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer.

JCO Clin Cancer Inform 2019 06;3:1-10

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: Compared with single-marker genetic testing (SMGT), multigene panel sequencing (MGPS) has the potential to identify more patients with cancer who could benefit from targeted therapies, but the effects on outcome and total cost of care are uncertain. Our goal was to estimate the clinical and cost effectiveness of MGPS versus SMGT among patients with advanced non-small-cell lung cancer (aNSCLC).

Methods: Patients with aNSCLC-stage IIIB or metastatic-who were diagnosed between 2011 and 2016 were identified from the Flatiron Health database. After stratifying patients into MGPS or SMGT cohorts, we analyzed the percentage of patients who received targeted treatment, survival, and total costs of care. SMGT included epidermal growth factor receptor () and anaplastic lymphoma kinase testing. MGPS also allowed for the detection of mutations. Cost data sources were the Centers for Medicare & Medicaid Services Fee Schedule and 2017 average sales price drug cost. We estimated the incremental cost-effectiveness ratio from a US payer perspective over a lifetime horizon using a decision model.

Results: We identified 5,688 patients with aNSCLC who received MGPS (n = 875) or SMGT (n = 4,813), of which 22% tested positive for epidermal growth factor receptor (18.5% MGPS; 17.3% SMGT) or anaplastic lymphoma kinase (3.59% MGPS; 3.78% SMGT). Among MGPS-tested patients, an additional 8% were found to have mutations. Of MGPS-tested patients, 21% received treatments that were targeted to the specific mutations versus 19% with SMGT. Expected survival was 1.14 life years (LYs) in SMGT versus 1.20 LYs in MGPS. Lifetime total costs were $8,814 higher per patient for MGPS. The incremental cost-effectiveness ratio of MGPS versus SMGT was $148,478 per LY gained.

Conclusion: On the basis of data from a nationwide oncology patient database, MGPS is shown to have moderate cost effectiveness compared with SMGT in patients with aNSCLC.
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http://dx.doi.org/10.1200/CCI.19.00002DOI Listing
June 2019

Development and validation of a model to predict outcomes of colon cancer surveillance.

Cancer Causes Control 2019 Jul 25;30(7):767-778. Epub 2019 May 25.

Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Purpose: Clinical trials suggest that intensive surveillance of colon cancer (CC) survivors to detect recurrence increases curative-intent treatment, although any survival benefit of surveillance as currently practiced appears modest. Realizing the potential of surveillance will require tools for identifying patients likely to benefit and for optimizing testing regimens. We describe and validate a model for predicting outcomes for any schedule of surveillance in CC survivors with specified age and cancer stage.

Methods: A Markov process parameterized based on individual-level clinical trial data generates natural history events for simulated patients. A utilization submodel simulates surveillance and diagnostic testing. We validate the model against outcomes from the follow-up after colorectal surgery (FACS) trial.

Results: Prevalidation sensitivity analysis showed no parameter influencing curative-intent treatment by > 5.0% or overall five-year survival (OS5) by > 1.5%. In validation, the proportion of recurring subjects predicted to receive curative-intent treatment fell within FACS 95% CI for carcinoembryonic antigen (CEA)-intensive, computed tomography (CT)-intensive, and combined CEA+CT regimens, but not for a minimum surveillance regimen, where the model overestimated recurrence and curative treatment. The observed OS5 fell within 95% prediction intervals for all regimens.

Conclusion: The model performed well in predicting curative surgery for three of four FACS arms. It performed well in predicting OS5 for all arms.
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http://dx.doi.org/10.1007/s10552-019-01187-xDOI Listing
July 2019

Comparative Effectiveness of Carboplatin/Pemetrexed With Versus Without Bevacizumab for Advanced Nonsquamous Non-Small Cell Lung Cancer.

J Natl Compr Canc Netw 2019 05;17(5):469-477

Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, and.

Background: Despite recent advances in targeted therapy and immunotherapy for advanced non-small cell lung cancer (NSCLC), carboplatin/pemetrexed/bevacizumab remains a commonly used first-line regimen. However, it is unknown whether the addition of bevacizumab to carboplatin/pemetrexed improves overall survival (OS).

Materials And Methods: Using nationally representative curated electronic health record data from Flatiron Health, we performed a retrospective cohort study of patients diagnosed with advanced nonsquamous NSCLC who received ≥1 cycle of carboplatin/pemetrexed ± bevacizumab as initial systemic therapy for stage IV or metastatic/recurrent disease. The OS impact of adding bevacizumab to carboplatin/pemetrexed was assessed using a Cox proportional hazards model to adjust for age, sex, race, original tumor stage, time between diagnosis of metastatic disease and start of chemotherapy, and performance status. In a secondary analysis of patients at a single academic institution, we also adjusted for the presence of brain metastases, hemoptysis, and anticoagulation.

Results: A total of 4,724 patients were included, of which 2,759 patients (58%) received carboplatin/pemetrexed and 1,965 (42%) received carboplatin/pemetrexed/bevacizumab. Median OS was 12.1 months (95% CI, 11.2-12.9 months) in the carboplatin/pemetrexed/bevacizumab group compared with 8.6 months (95% CI, 8.1-9.1 months) in the carboplatin/pemetrexed group (P<.001). Bevacizumab use remained associated with improved OS in a multivariate model (hazard ratio, 0.80; 95% CI, 0.75-0.86; P<.001). In the secondary, institutional analysis (N=539), the effect of bevacizumab was unchanged (hazard ratio, 0.75; 95% CI, 0.59-0.96; P=.02).

Conclusions: In this large, real-world dataset, the addition of bevacizumab to first-line carboplatin/pemetrexed for metastatic nonsquamous NSCLC was associated with improved OS.
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http://dx.doi.org/10.6004/jnccn.2018.7102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661525PMC
May 2019

Recommendations of Active Surveillance for Intermediate-risk Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists.

Eur Urol Oncol 2019 03 31;2(2):189-195. Epub 2018 Aug 31.

Cancer Outcomes and Public Policy Effectiveness Research Center, Yale University, New Haven, CT, USA; Department of Medicine, Yale University, New Haven, CT, USA.

Background: While active surveillance (AS) for intermediate-risk prostate cancer (PCa) remains controversial, perceptions of AS and treatment recommendations among PCa specialists are largely unknown. Thus, we performed a national survey of radiation oncologists (ROs) and urologists (UROs) to elicit attitudes and AS recommendations for intermediate-risk PCa.

Objective: To determine whether AS for PCa is becoming readily accepted by PCa specialists in the USA.

Design, Setting, And Participants: From January to July 2017, we conducted a national survey of 915 ROs and 940 UROs on perceptions of AS and its use among patients with intermediate-risk PCa.

Outcome Measurements And Statistical Analysis: Perceived effectiveness and comfort with AS and recommendation of AS from case presentations represented the primary outcomes. Pearson chi-square and multivariable logistic regression analyses were used to identify physician characteristics associated with primary outcomes.

Results And Limitations: Overall, the response rate was 37.3% (n=692) and was similar for ROs and UROs (35.7% vs 38.7%; p=0.18). For intermediate-risk PCa, both UROs and ROs expressed limited favorable views that AS is effective (39.8% vs 33.0%; p=0.06) and felt comfortable recommending it (37.6% vs 25.9%; p=0.001). From clinical scenarios, both specialties infrequently recommended AS for a healthy patient diagnosed with intermediate-risk PCa. For a healthy 55-yr-old patient with PSA of 8ng/ml and Gleason 3+4 PCa, few ROs and UROs recommended AS (2.8% vs 4.3%; adjusted odds ratio [AOR] 0.42; p=0.12). AS was more likely to be recommended equally by ROs and UROs for a healthy 75-yr-old with the same clinicopathologic characteristics (29.0% vs 35.4%; AOR 0.68; p=0.09). Limitations include a modest response rate for our survey.

Conclusions: Our national survey revealed that many ROs and UROs do not believe that AS is effective or feel comfortable recommending it or selecting it as an option for younger patients with intermediate-risk PCa.

Patient Summary: We performed a national survey of radiation oncologists and urologists to assess attitudes regarding active surveillance (AS) and its use among patients with intermediate-risk prostate cancer. Our study demonstrates that radiation oncologists and urologists are not yet comfortable with recommending AS and rarely endorse its use for younger patients.
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http://dx.doi.org/10.1016/j.euo.2018.08.004DOI Listing
March 2019

Trends in Checkpoint Inhibitor Therapy for Advanced Urothelial Cell Carcinoma at the End of Life: Insights from Real-World Practice.

Oncologist 2019 06 3;24(6):e397-e399. Epub 2019 Apr 3.

Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Several immune checkpoint inhibitor therapies (CPIs) have been approved to treat metastatic urothelial cell carcinoma (mUC). Because of the favorable toxicity profile of CPI compared with chemotherapy, oncologists may have a low threshold to prescribe CPI to patients near the end of life. We evaluated trends in initiation of end-of-life systemic therapy in 1,637 individuals in the Flatiron Health Database who were diagnosed with mUC between 2015 and 2017 and who died. Rates of systemic therapy initiation in the last 30 and 60 days of life were 17.0% and 29.8%, respectively. The quarterly proportion of patients who initiated CPI within 60 days of death increased from 1.0% to 23% during the study period ( < .001). After CPI approval, end-of-life CPI initiation significantly increased among patients with poor performance status ( = .020) and did not significantly change among individuals with good performance status. The quarterly proportion of patients who initiated any systemic therapy at the end of life doubled (17.4% to 34.8%) during the study period, largely explained by increased CPI use. These findings suggest a dramatic rise in CPI use at the end of life in patients with mUC, a finding that may have important guideline and policy implications.
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http://dx.doi.org/10.1634/theoncologist.2019-0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656487PMC
June 2019

Disease Control With FOLFIRI Plus Ziv-aflibercept (zFOLFIRI) Beyond FOLFIRI Plus Bevacizumab: Case Series in Metastatic Colorectal Cancer (mCRC).

Front Oncol 2019 14;9:142. Epub 2019 Mar 14.

Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, PA, United States.

The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. The utility of zFOLFIRI after bevacizumab+FOLFIRI is unknown and not recommended in NCCN guidelines. We explored whether zFOLFIRI may be active beyond progression on bevacizumab+FOLFIRI. We undertook a retrospective analysis of patients treated in routine clinical practice. A chart review was conducted for a cohort ( = 19) of advanced cancer patients (18 mCRC) who received zFOLFIRI from 2014 to 2018 at Fox Chase Cancer Center (FCCC). Analysis included time on zFOLFIRI, PFS, OS, CEA trends and adverse events. A second mCRC cohort ( = 26) from the Flatiron Health EHR-derived database treated with zFOLFIRI after prior bevacizumab+FOLFOX and bevacizumab+FOLFIRI was analyzed for time-on-treatment and overall survival. Median age of mCRC cohort at zFOLFIRI treatment was 54 (FCCC; = 18) and 62 (Flatiron Health-cohort; = 26). Of 18 FCCC mCRC patients, 1 patient had prior bevacizumab+FOLFOX and ramucirumab+irinotecan prior to zFOLFIRI for 8.5 months. Of 17 FCCC mCRC patients with prior bevacizumab+FOLFIRI who received zFOLFIRI, 13 had mutant-KRAS, 3 WT-KRAS, and one BRAF-V600E. The patient with BRAF-V600E mutation achieved stable disease on zFOLFIRI after multiple BRAF-targeted therapies. One patient (WT-KRAS mCRC) remained on zFOLFIRI for 14 months. Of 14 patients with mutated-KRAS, 8 remained on zFOLFIRI for >5 months including 3 for >15 months. The rate-of-change in CEA measures on zFOLFIRI was significantly different ( = 0.004) between rapid progressors and those with PFS>4 months. For mCRC patients treated with zFOLFIRI in the 3rd line or greater ( = 18), median PFS was 7.1 months (214 days) and median OS was 13.8 months (416 days). Median time-on-treatment with zFOLFIRI in the Flatiron Health cohort was 4.4 months, median OS was 7.8 months, and longest time-on-treatment with zFOLFIRI was 266 days. In these small real-world cohorts, clinical meaningful stable disease and overall survival on zFOLFIRI beyond progression on bevacizumab+FOLFIRI was observed in patients with mCRC. Further exploration of this approach is warranted.
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http://dx.doi.org/10.3389/fonc.2019.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426764PMC
March 2019

Opportunities for using big data to advance cancer care.

Authors:
Neal J Meropol

Clin Adv Hematol Oncol 2018 Dec;16(12):807-809

Flatiron Health, New York, New York.

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December 2018

A National Study of Oncology Nurses Discussing Cancer Clinical Trials With Patients.

West J Nurs Res 2019 12 19;41(12):1747-1760. Epub 2019 Feb 19.

Case Western Reserve University, Cleveland, OH, USA.

In the United States less than 10% of cancer patients engage in clinical trials. Although most oncology nurses have multiple opportunities to discuss clinical trials with patients, barriers including attitudes and social norms may impede these discussions. Guided by the Theory of Planned Behavior, we developed and evaluated measures for attitudes, subjective norms, and perceived behavioral control of nurses for discussing clinical trials with cancer patients. Of the 18,000 Oncology Nurse Society members invited, 1,964 completed the survey. Structural equation modeling and internal consistency reliability were used to evaluate items and constructs. We found that overall model fit and reliability was good: Confirmatory Fit Index (CFI) = 0.91, Root Mean Square Error of Approximation (RMSEA) = 0.05; attitudes, 21 items, alpha = 0.84; perceived behavioral control, 10 items, alpha = 0.85; and subjective norms, 9 items, alpha = 0.89. These measures of attitudes, subjective norms, and perceived behavioral control show good reliability and initial evidence of validity.
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http://dx.doi.org/10.1177/0193945919829145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699918PMC
December 2019
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