Lung cancer prediction in Lambert-Eaton myasthenic syndrome in a prospective cohort

Paul Maddison,Bethan Lang,Paul Gozzard,Jan J Verschuuren,Girija Sadalage,Philip A Ambrose,Alexander F Lipka

doi:10.1038/s41598-020-67571-9

Abstract

To evaluate the Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumour Association Prediction (DELTA-P) score in a prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting. Clinical features from 87 patients with LEMS, occurring within three months from disease onset, were collated to produce a DELTA-P score for each patient. Lung cancer was detected in 44/87 (51%) LEMS patients. Weight loss ≥ 5%, tobacco use at LEMS onset and age at onset ≥ 50 years were independent predictors for the development of small-cell lung cancer (SCLC) in LEMS patients in multivariable analysis. Median DELTA-P scores were significantly higher in SCLC-LEMS patients (3.5, 95% CI 3 to 4) compared to non-tumour-LEMS (2, 95% CI 1 to 2) (P < 0.0001). Higher DELTA-P scores increased the risk of SCLC stepwise (score 0 = 0%, 1 = 18.8%, 2 = 45%, 3 = 55.5%, 4 = 85.7%, 5 = 87.5%, 6 = 100%). The area under the curve of the receiver operating curve was 82.5% (95% CI 73.9% to 91%). The DELTA-P cancer prediction score, calculated at the time of LEMS diagnosis, is an effective tool for cancer screening in an independent, prospective study setting.

Highlights

To evaluate the Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumour Association Prediction (DELTA-P) score in a prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting
The median time between LEMS diagnosis and small-cell lung cancer (SCLC) confirmation was 0.5 months: the tumour was diagnosed within six months in 91% and within 12 months in 98% of SCLC-LEMS patients
We have previously developed a highly effective clinical scoring system (DELTA-P) for predicting SCLC development in patients with newly diagnosed LEMS8, given that approximately half of all patients with LEMS develop this type of lung cancer

Summary

Introduction

To evaluate the Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumour Association Prediction (DELTA-P) score in a prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting. We have previously developed and validated a cancer prediction clinical scoring system in Dutch and UK cohorts of LEMS patients from retrospectively collected data (Dutch-English LEMS Tumour Association Prediction, or DELTA-P, score), which discriminated highly between SCLC-LEMS and NT-LEMS, applicable at the time of LEMS d iagnosis[8] The objective of this current study was to evaluate the DELTA-P score for cancer prediction in a new, prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting. Number Median age in years (range) at LEMS diagnosis Aged ≥ 50 years Proportion female Bulbar/neck weakness Sexual impotencea Male sexual impotence Weight loss ≥ 5% Smoking at LEMS onset Karnofsky performance score < 70 Dry mouthb Proximal upper limb weaknessc Median survival from LEMS diagnosis (months) (Log rank) Positive P/Q-type VGCC antibodies (median titre)

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