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      The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting

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          Abstract

          Background

          Despite the availability of effective antiemetics and evidence-based guidelines, up to 40% of cancer patients receiving chemotherapy fail to achieve complete nausea and vomiting control. In addition to type of chemotherapy, several patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) have been identified. To incorporate these factors into the optimal selection of prophylactic antiemetics, a repeated measures cycle-based model to predict the risk of ≥ grade 2 CINV (≥2 vomiting episodes or a decrease in oral intake due to nausea) from days 0 to 5 post-chemotherapy was developed.

          Patients and methods

          Data from 1198 patients enrolled in one of the five non-interventional CINV prospective studies were pooled. Generalized estimating equations were used in a backwards elimination process with the P-value set at <0.05 to identify the relevant predictive factors. A risk scoring algorithm (range 0–32) was then derived from the final model coefficients. Finally, a receiver-operating characteristic curve (ROCC) analysis was done to measure the predictive accuracy of the scoring algorithm.

          Results

          Over 4197 chemotherapy cycles, 42.2% of patients experienced ≥grade 2 CINV. Eight risk factors were identified: patient age <60 years, the first two cycles of chemotherapy, anticipatory nausea and vomiting, history of morning sickness, hours of sleep the night before chemotherapy, CINV in the prior cycle, patient self-medication with non-prescribed treatments, and the use of platinum or anthracycline-based regimens. The ROC analysis indicated good predictive accuracy with an area-under-the-curve of 0.69 (95% CI: 0.67–0.70). Before to each cycle of therapy, patients with risk scores ≥16 units would be considered at high risk for developing ≥grade 2 CINV.

          Conclusions

          The clinical application of this prediction tool will be an important source of individual patient risk information for the oncology clinician and may enhance patient care by optimizing the use of the antiemetics in a proactive manner.

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          Most cited references31

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.

            The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model. Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects. We evaluated several variants of split-sample, cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infarction. Random samples with a size between n = 572 and n = 9165 were drawn from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in data sets with between 5 and 80 events per variable. Independent performance was determined on the remaining subjects. Performance measures included discriminative ability, calibration and overall accuracy. We found that split-sample analyses gave overly pessimistic estimates of performance, with large variability. Cross-validation on 10% of the sample had low bias and low variability, but was not suitable for all performance measures. Internal validity could best be estimated with bootstrapping, which provided stable estimates with low bias. We conclude that split-sample validation is inefficient, and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model.
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              2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.

              To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.
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                Author and article information

                Journal
                Ann Oncol
                Ann. Oncol
                annonc
                Annals of Oncology
                Oxford University Press
                0923-7534
                1569-8041
                June 2017
                07 April 2017
                07 April 2017
                : 28
                : 6
                : 1260-1267
                Affiliations
                [1 ]The Ottawa Hospital Regional Cancer Centre, Ottawa, Canada;
                [2 ]Hong Kong Polytechnic University, Hong Kong;
                [3 ]UC San Diego Moores Cancer Center, La Jolla;
                [4 ]The West Clinic, Memphis, USA;
                [5 ]Institut de Cancérologie Gustave Roussy, Villejuif, France;
                [6 ]Department of Medicine V, University of Heidelberg, Heidelberg, Germany;
                [7 ]Cancer Research Center, University of Warwick, Conventry, UK;
                [8 ]Cancer Center, Clinique de Genolier, Genolier, Switzerland
                Author notes
                [* ] Correspondence to: Dr George Dranitsaris, The Ottawa Hospital Regional Cancer Centre, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6. Tel: +1-416-461-2720; Fax: +1-416-461-4735; E-mail: george.dranitsaris@ 123456gmail.com
                Article
                mdx100
                10.1093/annonc/mdx100
                5452068
                28398530
                8b4ecc0d-e044-4369-b14e-24ab7a1c69b6
                © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Page count
                Pages: 8
                Categories
                Original Articles
                Supportive Care
                Editor's Choice

                Oncology & Radiotherapy
                emesis,nausea,risk,prediction,cancer,cinv
                Oncology & Radiotherapy
                emesis, nausea, risk, prediction, cancer, cinv

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