Risk of childhood cancer with symptoms in primary care: a population-based case-control study

Guidelines describing symptoms in children that should alert GPs to consider cancer have been developed, but without any supporting primary-care research. To identify symptoms and signs in primary care that strongly increase the likelihood of childhood cancer, to assist GPs in selection of children for investigation. A population-based case-control study in UK general practice. Using electronic primary care records from the UK General Practice Research Database, 1267 children aged 0-14 years diagnosed with childhood cancer were matched to 15 318 controls. Clinical features associated with subsequent diagnosis of cancer were identified using conditional logistic regression, and likelihood ratios and positive predictive values (PPVs) were estimated for each. Twelve symptoms were associated with PPVs of ≥0.04%, which represents a greater than tenfold increase in prior probability. The six symptoms with the highest PPVs were pallor (odds ratio, OR = 84; PPV = 0.41% (95% confidence interval [CI] = 0.12% to 1.34%), head and neck masses (OR = 17; PPV = 0.30%; 95% CI = 0.10% to 0.84%), masses elsewhere (OR = 22; PPV = 0.11%; 95% CI = 0.06% to 0.20%), lymphadenopathy (OR = 10; PPV = 0.09%; 95% CI = 0.06% to 0.13%), symptoms/signs of abnormal movement (OR = 16; PPV = 0.08%; 95% CI = 0.04% to 0.14%), and bruising (OR = 12; PPV = 0·08%; 95% CI = 0.05% to 0.13%). When each of these 12 symptoms was combined singly with at least three consultations in a 3-month period, the probability of cancer was between 11 and 76 in 10 000. Twelve features of childhood cancers were identified, each of which increased the risk of cancer at least tenfold. These symptoms, particularly when combined with multiple consultations, warrant careful evaluation in general practice.