Late, persistent, substantial, treatment-related symptoms after radiotherapy (LAPERS): A new method for longitudinal analysis of late morbidity - applied in the EMBRACE study

Forfattere Kirchheiner K, Pötter R, Nout RA, Schwartz-Vittrup A, Holzner B, Bentzen SM, Tanderup K
Kilde Int J Radiat Oncol Biol Phys. 2020 Feb 1;106(2):300-309 Publiceringsdato 25 okt 2019


Current incidence methods for reporting mild/moderate symptoms capture the (first) occurrence of an event and do not allow distinguishing between patients who suffer from long-lasting vs. transient morbidity. This paper introduces a new methodological approach which identifies cancer survivors who have clinically relevant, long-lasting symptoms (patients with late, persistent,  substantial and treatment-related symptoms, "LAPERS").


LAPERS can be evaluated in patients with baseline information and at least 3 late follow-up assessments after treatment. LAPERS identifies individual patients with a given symptom that is substantial (above a pre-defined clinically relevant threshold) and must be present in at least half of the follow-ups. Baseline morbidity is accounted for by requiring the median of the late symptom score to be worse than the baseline condition. The LAPERS approach was applied to four relevant patient-reported genito-urinary/gastro-intestinal symptoms (EORTC-QLQ) within the prospective, longitudinal XXX study (XXX for locally advanced cervical cancer, www.XXX). LAPERS was compared to crude incidence and prevalence rates.


Within the XXX cohort, 651/1044 patients (62%) had baseline and long-term follow-up available (median follow-up: 42 months). There was a considerable gap between LAPERS, crude incidence and prevalence rates. The proportion of patients with LAPERS events was 3.8-4.8 times lower than crude incidences. The highest prevalence rates across follow-up times were 1.8-2.6 times lower than crude incidences.


These findings indicate limitations of incidence methods for reporting substantial patient-reported symptoms, since a considerable proportion of patients with symptoms do not experience them persistently over time, as they may fluctuate or get successfully treated. In contrast, the LAPERS method for longitudinal analysis identifies patients with clinically relevant, long-lasting symptoms.