Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.

<h4>Background</h4>Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combi...

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Autores principales:	Brian D Nicholson, Paul Aveyard, Constantinos Koshiaris, Rafael Perera, Willie Hamilton, Jason Oke, F D Richard Hobbs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/f427d7562aed4ca499f261452b33e506
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spelling	oai:doaj.org-article:f427d7562aed4ca499f261452b33e5062021-12-02T19:55:37ZCombining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.1549-12771549-167610.1371/journal.pmed.1003728https://doaj.org/article/f427d7562aed4ca499f261452b33e5062021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1003728https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.<h4>Methods and findings</h4>We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.<h4>Conclusions</h4>Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.Brian D NicholsonPaul AveyardConstantinos KoshiarisRafael PereraWillie HamiltonJason OkeF D Richard HobbsPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 18, Iss 8, p e1003728 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Brian D Nicholson Paul Aveyard Constantinos Koshiaris Rafael Perera Willie Hamilton Jason Oke F D Richard Hobbs Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
description	<h4>Background</h4>Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.<h4>Methods and findings</h4>We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.<h4>Conclusions</h4>Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.
format	article
author	Brian D Nicholson Paul Aveyard Constantinos Koshiaris Rafael Perera Willie Hamilton Jason Oke F D Richard Hobbs
author_facet	Brian D Nicholson Paul Aveyard Constantinos Koshiaris Rafael Perera Willie Hamilton Jason Oke F D Richard Hobbs
author_sort	Brian D Nicholson
title	Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
title_short	Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
title_full	Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
title_fullStr	Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
title_full_unstemmed	Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
title_sort	combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: clinical risk score development, internal validation, and net benefit analysis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f427d7562aed4ca499f261452b33e506
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Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.

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