Quantifying the risk of non-Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a large case-control study using electronic records

Abstract

Background: Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in the UK; approximately 35 people are diagnosed and 13 die from the disease daily.

Aim: To identify the primary care clinical features of NHL and quantify their risk in symptomatic patients.

Design and setting: Matched case-control study using Clinical Practice Research Datalink patient records.

Method: Putative clinical features of NHL were identified in the year before diagnosis. Results were analysed using conditional logistic regression and positive predictive values (PPVs).

Results: A total of 4362 patients aged ≥40 years, diagnosed with NHL between 2000 and 2009, and 19 468 age, sex, and general practice-matched controls were studied. Twenty features were independently associated with NHL. The five highest risk symptoms were lymphadenopathy, odds ratio (OR) 263 (95% CI = 133 to 519), head and neck mass not described as lymphadenopathy OR 49 (95% CI = 32 to 74), other mass OR 12 (95% CI = 10 to 16), weight loss OR 3.2 (95% CI = 2.3 to 4.4), and abdominal pain OR 2.5 (95% CI = 2.1 to 2.9). Lymphadenopathy has a PPV of 13% for NHL in patients ≥60 years. Weight loss in conjunction with repeated back pain or raised gamma globulin had PPVs >2%.

Conclusion: Unexplained lymphadenopathy in patients aged ≥60 years produces a very high risk of NHL in primary care. These patients warrant urgent investigation, potentially sooner than 6 weeks from initial presentation where the GP is particularly concerned.

Keywords: cancer; clinical features; diagnosis; lymphadenopathy; non-Hodgkin lymphoma; primary health care.

Figure 1.

Non-Hodgkin lymphoma exclusion data.

Figure 2.

Positive predictive values for non-Hodgkin lymphoma symptoms in patients aged ≥ 60 years, for single and paired features. Notes: The positive predictive value (PPV) is shown on the first line of each cell with the 95% CIs shown underneath. PPVs were not calculated if < 5 cases had the feature. Where < 10 cases or controls had the combined features, CIs were omitted. Where no control had the combination of paired symptoms a label of > 5 or > 10 was given; although strictly undefined, these PPVs are likely very high. The yellow shaded cells indicate a PPV of 1.0–1.9%; orange cells 2.0–4.9%; and red cells ≥ 5%. The cells showing the same feature vertically and horizontally represent a second attendance with the same investigation.

Figure 3.

Positive predictive values for non-Hodgkin lymphoma blood tests with symptoms in patients aged ≥ 60 years: risk estimate for single investigations and paired with symptoms. Notes: The positive predictive value (PPV) is shown on the first line of each cell with the 95% CIs shown underneath. PPVs were not calculated if < 5 cases had the feature. Where < 10 cases or controls had the combined features, CIs were omitted. Where no control had the combination of paired symptoms a label of > 5 or > 10 was given; although strictly undefined, these PPVs are likely very high. The yellow shaded cells indicate a PPV of 1.0–1.9%; orange cells 2.0–4.9%; and red cells ≥ 5%. The cells showing the same feature vertically and horizontally represent a second attendance with the same investigation.