Persistence of Late Substantial Patient-Reported Symptoms (LAPERS) After Radiochemotherapy Including Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: A Report From the EMBRACE Study

A.S. Vittrup*, K. Tanderup, S.M. Bentzen, N.B.K. Jensen, S. Spampinato, L.U. Fokdal, J.C. Lindegaard, A. Sturdza, M. Schmid, B. Segedin, I.M. Jurgenliemk-Schulz, K. Bruheim, U. Mahantshetty, C. Haie-Meder, B. Rai, R. Cooper, E. Van der Steen-Banasik, M. Sundset, F. Huang, R.A. NoutE. Villafranca, E. Van Limbergen, B.R. Pieters, L. Tan, L.C.H.W. Lutgens, P. Hoskin, R. Potter, K. Kirchheiner, EMBRACE Collaborative Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC).Methods and Materials: Patient-reported symptoms (European Organization for Research and Treatment of Cancer [EORTC]-C30/CX24) and physician-assessed morbidity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were assessed at baseline and regular timepoints during follow-up. Patients with sufficient EORTC follow-up (baseline and >= 3 late follow-up visits) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms (quite a bit/very much) for at least half of the assessments (persistence) and progression beyond baseline condition (treatment-related). For each EORTC symptom, the ratio between LAPERS rates and crude incidence rates of substantial symptoms was calculated to represent the proportion of symptomatic patients with persisting symptoms. For 9 symptoms with a corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (grades 3-5) was evaluated.Results: Of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. The median follow-up was 59 months (interquartile range, 42-70 months). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range, 0.0% vaginal bleeding to 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stool, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of <1%. A median of 19% of symptomatic patients (interquartile range, 8.0%-28.5%) showed persistent long-term symptoms (LAPERS events). In symptoms with a corresponding EORTC/CTCAE assessment, 12% of LAPERS events were accompanied by a severe CTCAE event.Conclusions: Within this large cohort of survivors of LACC, a subgroup of patients with persistent symptoms (LAPERS events) was identified. For symptoms with a corresponding EORTC/CTCAE assessment, the vast majority of LAPERS events occurred in patients without corresponding severe physician-assessed morbidity. These findings emphasize the importance of distinguishing between transient and persisting symptoms in the aftercare of LACC survivors. (C) 2020 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)161-173
Number of pages13
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number1
Publication statusPublished - 1 Jan 2021


  • carcinoma
  • chemoradiation
  • clinical-trials
  • european-organization
  • gastrointestinal symptoms
  • incontinence
  • pelvic radiotherapy
  • quality-of-life
  • radiation-therapy
  • recommendations

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