Neal J Meropol

Case Western Reserve University, Cleveland, Ohio, United States

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Publications (251)1697.7 Total impact

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    ABSTRACT: Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 3% of colorectal cancers are associated with Lynch Syndrome. Controversy exists regarding the optimal screening strategy for Lynch Syndrome. Using an individual level microsimulation of a population affected by Lynch syndrome over several years, effectiveness and cost-effectiveness of 21 screening strategies were compared. Modeling assumptions were based upon published literature, and sensitivity analyses were performed for key assumptions. In a two-step process, the number of Lynch syndrome diagnoses (Step 1) and life-years gained as a result of foreknowledge of Lynch syndrome in otherwise healthy carriers (Step 2) were measured. The optimal strategy was sequential screening for probands starting with a predictive model, then immunohistochemistry for mismatch repair protein expression (IHC), followed by germline mutation testing (incremental cost-effectiveness ratio [ICER] of $35 143 per life-year gained). The strategies of IHC + BRAF, germline testing and universal germline testing of colon cancer probands had ICERs of $144 117 and $996 878, respectively. This analysis suggests that the initial step in screening for Lynch Syndrome should be the use of predictive models in probands. Universal tumor testing and general population screening strategies are not cost-effective. When family history is unavailable, alternate strategies are appropriate. Documentation of family history and screening for Lynch Syndrome using a predictive model may be considered a quality-of-care measure for patients with colorectal cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    CancerSpectrum Knowledge Environment 04/2015; 107(4). DOI:10.1093/jnci/djv005 · 15.16 Impact Factor
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    ABSTRACT: Combination therapy with trabectedin and docetaxel was evaluated in patients with advanced malignancies. In this open-label phase 1 study, docetaxel (60 or 75 mg/m(2); 1-h intravenous infusion) was given on day 1 of a 21-day cycle in combination with escalating doses of trabectedin (0.4-1.3 mg/m(2) by 3-h intravenous infusion, 1 h after docetaxel) and prophylactic granulocyte colony-stimulating factor (G-CSF). Maximum tolerated dose (MTD) as primary objective and safety, plasma pharmacokinetics, and antitumor activity as secondary objectives were assessed. Patients (N = 49) received a median of four cycles of treatment. MTD was 1.3 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with limited and 1.1 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with unlimited prior chemotherapy. Dose-limiting toxicities (during cycle 1) included elevated alanine aminotransferase (ALT) and fatigue in patients with limited prior chemotherapy and elevated ALT and febrile neutropenia in those with unlimited prior chemotherapy. The most common drug-related adverse events were nausea (65 %), fatigue (63 %), and neutropenia (53 %). One patient achieved a complete response. Thirty patients had stable disease, and 11 had stable disease for ≥6 months. Pharmacokinetic results for trabectedin plus docetaxel were similar to those previously reported for the single agents. In patients with previously treated, advanced malignancies, the combination of therapeutic doses of trabectedin and docetaxel showed clinical activity and was tolerable with prophylactic G-CSF, with no evidence of clinically important drug interactions.
    Cancer Chemotherapy and Pharmacology 03/2015; DOI:10.1007/s00280-015-2705-z · 2.57 Impact Factor
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    ABSTRACT: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.British Journal of Cancer advance online publication 10 March 2015; doi:10.1038/bjc.2015.73 www.bjcancer.com.
    British Journal of Cancer 03/2015; DOI:10.1038/bjc.2015.73 · 4.82 Impact Factor
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    ABSTRACT: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m(2)/d Monday-Friday) plus irinotecan (50 mg/m(2)/wk × 4); and (2) capecitabine (1650 mg/m(2)/d Monday-Friday) plus oxaliplatin (50 mg/m(2)/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m(2); leucovorin 400 mg/m(2); 5-fluorouracil 400 mg/m(2); 5-fluorouracil 2400 mg/m(2)) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local-regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 11/2014; 91(1). DOI:10.1016/j.ijrobp.2014.09.031 · 4.18 Impact Factor
  • Lowell E Schnipper, Neal J Meropol
    Journal of Clinical Oncology 11/2014; 32(36). DOI:10.1200/JCO.2014.57.9573 · 17.88 Impact Factor
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    ABSTRACT: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer.
    Radiotherapy and Oncology 10/2014; 113(1). DOI:10.1016/j.radonc.2014.08.014 · 4.86 Impact Factor
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    ABSTRACT: Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice.
    Journal of Oncology Practice 07/2014; DOI:10.1200/JOP.2014.001439
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    ABSTRACT: Objective This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials. Methods The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N = 100) from the randomized trial. Results Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool's user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos. Conclusion The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice Implications. Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools.
    Patient Education and Counseling 07/2014; 96(1). DOI:10.1016/j.pec.2014.04.009 · 2.60 Impact Factor
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    ABSTRACT: Background:This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization.Methods:Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine.Results:Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively.Conclusions:This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.British Journal of Cancer advance online publication, 1 July 2014; doi:10.1038/bjc.2014.344 www.bjcancer.com.
    British Journal of Cancer 07/2014; DOI:10.1038/bjc.2014.344 · 4.82 Impact Factor
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    ABSTRACT: Background Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0-2 prior therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate. A Simon two-stage design was employed (null response rate of < 5% and response rate of ≥ 20% of interest). Results Twenty patients enrolled: bile duct/gallbladder cancer (14/6), prior treatments 0/1/2 (10/6/3). The trial was discontinued early due to lack of confirmed partial responses. No unanticipated adverse events were noted. There was one unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% CI 0.7-77.6 months). Median survival was 9 months (95% CI 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%. There was no difference in survival based on primary disease site. Conclusions Single agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.
    Clinical Colorectal Cancer 06/2014; 13(2). DOI:10.1016/j.clcc.2013.12.005 · 2.91 Impact Factor
  • Cheng E Chee, Neal J Meropol
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    ABSTRACT: The decision regarding adjuvant therapy for patients with stage II colon cancer remains a challenge. In contrast to stage III colon cancer, for which compelling clinical data support the use of adjuvant chemotherapy, the clinical benefit of systemic therapy in unselected patients with stage II disease is modest at best. Risk stratification based on clinicopathologic features and DNA mismatch repair status is commonly used in adjuvant therapy decisions, but these factors do not have a desired level of precision in identifying patients at high risk. Recently, gene expression platforms have been developed to further define risk and to assist in therapeutic decision making for patients with stage II disease. This review describes those platforms that are furthest along in clinical development, in an effort to place their potential clinical application in context.
    The Oncologist 05/2014; 19(7). DOI:10.1634/theoncologist.2013-0471 · 4.54 Impact Factor
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    ABSTRACT: Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42 %) had a personal cancer history, while 56 % had ≥1 first-degree relative with colorectal cancer. Overall, 21.3 % were willing to have testing only if paid by insurance, and 78.7 % were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p < 0.05). Subjects willing-to-pay a higher amount were male, more educated, had greater cancer worry, fewer relatives with colorectal cancer, and more positive attitudes toward genetic testing (all p < 0.05). Individuals seeking risk assessment are willing-to-pay out-of-pocket for genetic testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.
    Journal of Genetic Counseling 05/2014; 23(6). DOI:10.1007/s10897-014-9724-5 · 1.75 Impact Factor
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    ABSTRACT: Approximately one-third of those treated curatively for colorectal cancer (CRC) will experience recurrence. No evidence-based consensus exists on how best to follow patients after initial treatment to detect asymptomatic recurrence. Here, a new approach for simulating surveillance and recurrence among CRC survivors is outlined, and development and calibration of a simple model applying this approach is described. The model's ability to predict outcomes for a group of patients under a specified surveillance strategy is validated. We developed an individual-based simulation model consisting of two interacting submodels: a continuous-time disease-progression submodel overlain by a discrete-time Markov submodel of surveillance and re-treatment. In the former, some patients develops recurrent disease which probabilistically progresses from detectability to unresectability, and which may produce early symptoms leading to detection independent of surveillance testing. In the latter submodel, patients undergo user-specified surveillance testing regimens. Parameters describing disease progression were preliminarily estimated through calibration to match five-year disease-free survival, overall survival at years 1-5, and proportion of recurring patients undergoing curative salvage surgery from one arm of a published randomized trial. The calibrated model was validated by examining its ability to predict these same outcomes for patients in a different arm of the same trial undergoing less aggressive surveillance. Calibrated parameter values were consistent with generally observed recurrence patterns. Sensitivity analysis suggested probability of curative salvage surgery was most influenced by sensitivity of carcinoembryonic antigen assay and of clinical interview/examination (i.e. scheduled provider visits). In validation, the model accurately predicted overall survival (59% predicted, 58% observed) and five-year disease-free survival (55% predicted, 53% observed), but was less accurate in predicting curative salvage surgery (10% predicted; 6% observed). Initial validation suggests the feasibility of this approach to modeling alternative surveillance regimens among CRC survivors. Further calibration to individual-level patient data could yield a model useful for predicting outcomes of specific surveillance strategies for risk-based subgroups or for individuals. This approach could be applied toward developing novel, tailored strategies for further clinical study. It has the potential to produce insights which will promote more effective surveillance--leading to higher cure rates for recurrent CRC.
    BMC Medical Informatics and Decision Making 04/2014; 14(1):29. DOI:10.1186/1472-6947-14-29 · 1.50 Impact Factor
  • Journal of Clinical Oncology 03/2014; 32(12). DOI:10.1200/JCO.2013.53.8009 · 17.88 Impact Factor
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    ABSTRACT: Comparative effectiveness research aims to inform health-care decisions by patients, clinicians, and policy makers. However, questions related to what information is relevant, and how to view the relative attributes of alternative interventions have political, social, and medical considerations. In particular, questions about whether cost is a relevant factor, and whether cost-effectiveness is a desirable or necessary component of such research, have become increasingly controversial as the area has gained prominence. Debate has emerged about whether comparative effectiveness research promotes rationing of cancer care. At the heart of this debate are questions related to the role and limits of patient autonomy, physician discretion in health-care decision making, and the nature of scientific knowledge as an objective good. In this article, we examine the role of comparative effectiveness research in the USA, UK, Canada, and other health-care systems, and the relation between research and policy. As we show, all health systems struggle to balance access to cancer care and control of costs; comparative effectiveness data can clarify choices, but does not itself determine policy or promote rationing of care.
    The Lancet Oncology 02/2014; 15(3). DOI:10.1016/S1470-2045(13)70597-7 · 24.73 Impact Factor
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    ABSTRACT: Patient participation in cancer clinical trials is low. Little is known about attitudinal barriers to participation, particularly among patients who may be offered a trial during an imminent initial oncology consult. The aims of the present study were to confirm the presence of proposed subscales of a recently developed cancer clinical trial attitudinal barriers measure, describe the most common cancer clinical trials attitudinal barriers, and evaluate socio-demographic, medical and financial factors associated with attitudinal barriers. A total of 1256 patients completed a survey assessing demographic factors, perceived financial burden, prior trial participation and attitudinal barriers to clinical trials participation. Results of a factor analysis did not confirm the presence of the proposed four attitudinal barriers subscale/factors. Rather, a single factor represented the best fit to the data. The most highly-rated barriers were fear of side-effects, worry about health insurance and efficacy concerns. Results suggested that less educated patients, patients with non-metastatic disease, patients with no previous oncology clinical trial participation, and patients reporting greater perceived financial burden from cancer care were associated with higher barriers. These patients may need extra attention in terms of decisional support. Overall, patients with fewer personal resources (education, financial issues) report more attitudinal barriers and should be targeted for additional decisional support.
    European Journal of Cancer Care 01/2014; 24(1). DOI:10.1111/ecc.12180 · 1.76 Impact Factor
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    ABSTRACT: Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy.
    Cancer informatics 01/2014; 13:157-66. DOI:10.4137/CIN.S19454
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    ABSTRACT: This study used the Ottawa Decision Support Framework to evaluate a model examining associations between clinical trial knowledge, attitudinal barriers to participating in clinical trials, clinical trial self-efficacy, and clinical trial preparedness among 1256 cancer patients seen for their first outpatient consultation at a cancer center. As an exploratory aim, moderator effects for gender, race/ethnicity, education, and metastatic status on associations in the model were evaluated. . Patients completed measures of cancer clinical trial knowledge, attitudinal barriers, self-efficacy, and preparedness. Structural equation modeling (SEM) was conducted to evaluate whether self-efficacy mediated the association between knowledge and barriers with preparedness. . The SEM explained 26% of the variance in cancer clinical trial preparedness. Self-efficacy mediated the associations between attitudinal barriers and preparedness, but self-efficacy did not mediate the knowledge-preparedness relationship. . Findings partially support the Ottawa Decision Support Framework and suggest that assessing patients' level of self-efficacy may be just as important as evaluating their knowledge and attitudes about cancer clinical trials.
    Medical Decision Making 11/2013; 34(4). DOI:10.1177/0272989X13511704 · 2.27 Impact Factor
  • Neal J Meropol
    CancerSpectrum Knowledge Environment 11/2013; 105(23). DOI:10.1093/jnci/djt334 · 15.16 Impact Factor

Publication Stats

12k Citations
1,697.70 Total Impact Points

Institutions

  • 2010–2015
    • Case Western Reserve University
      • Case Comprehensive Cancer Center
      Cleveland, Ohio, United States
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 2009–2014
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
  • 1998–2014
    • Fox Chase Cancer Center
      • Department of Medical Oncology
      Filadelfia, Pennsylvania, United States
  • 2013
    • The Ohio State University
      Columbus, Ohio, United States
  • 1992–2009
    • University of Pennsylvania
      • Division of Hematology/Oncology
      Philadelphia, Pennsylvania, United States
    • Mount Sinai Hospital
      New York City, New York, United States
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2008
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 2004–2008
    • Duke University
      Durham, North Carolina, United States
  • 1993–2007
    • Hospital of the University of Pennsylvania
      • • Department of Radiation Oncology
      • • Division of Hematology/Oncology
      Philadelphia, Pennsylvania, United States
  • 2000–2004
    • Temple University
      Philadelphia, Pennsylvania, United States
  • 1994–1999
    • Roswell Park Cancer Institute
      • • Department of Surgical Oncology
      • • Department of Medicine
      Buffalo, New York, United States
  • 1991
    • University of Washington Seattle
      Seattle, Washington, United States