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.

Forfattere Vittrup AS, Tanderup K, Bentzen SM, Jensen NBK, Spampinato S, Fokdal LU, Lindegaard JC, Sturdza A, Schmid M, Segedin B, Jürgenliemk-Schulz IM, Bruheim K, Mahantshetty U, Haie-Meder C, Rai B, Cooper R, van der Steen-Banasik E, Sundset M, Huang F, Nout RA, Villafranca E, Van Limbergen E, Pieters BR, Tan LT, Lutgens LCHW, Hoskin P, Pötter R, Kirchheiner K; EMBRACE Collaborative Group.
Kilde Int J Radiat Oncol Biol Phys. 2020 Aug 24;S0360-3016(20)34139-0. Publiceringsdato 24 aug 2020


This report describes persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional XXX study on MR image-guided adaptive brachytherapy in locally advanced cervical cancer (LACC).


Patient-reported symptoms (EORTC-C30/CX24) and physician-assessed morbidity (CTCAEv.3.0) were assessed at baseline and regular time points during follow-up. Patients with sufficient EORTC follow-up (baseline and ≥3 late follow-ups) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms ("quite a bit"/"very much") for at least half of 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 corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (G3-5) was evaluated.


Out of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. Median follow-up was 59 months (IQR 42-70). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range: 0.0% vaginal bleeding - 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stools, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of <1%. In median, 19% of symptomatic patients (IQR 8.0-28.5%) showed persistent long-term symptoms (LAPERS events). In symptoms with corresponding EORTC/CTCAE assessment, 12% of LAPERS events were accompanied by a severe CTCAE event.


Within this large cohort of LACC survivors, a subgroup of patients with persistent symptoms (LAPERS events) was identified. For symptoms with 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.