TY - JOUR
T1 - 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
AU - Vittrup, A.S.
AU - Tanderup, K.
AU - Bentzen, S.M.
AU - Jensen, N.B.K.
AU - Spampinato, S.
AU - Fokdal, L.U.
AU - Lindegaard, J.C.
AU - Sturdza, A.
AU - Schmid, M.
AU - Segedin, B.
AU - Jurgenliemk-Schulz, I.M.
AU - Bruheim, K.
AU - Mahantshetty, U.
AU - Haie-Meder, C.
AU - Rai, B.
AU - Cooper, R.
AU - Van der Steen-Banasik, E.
AU - Sundset, M.
AU - Huang, F.
AU - Nout, R.A.
AU - Villafranca, E.
AU - Van Limbergen, E.
AU - Pieters, B.R.
AU - Tan, L.
AU - Lutgens, L.C.H.W.
AU - Hoskin, P.
AU - Potter, R.
AU - Kirchheiner, K.
AU - EMBRACE Collaborative Grp
N1 - Funding Information:
The EMBRACE study was supported by Elekta AB and Varian Medical System through unrestricted research grants and study sponsoring through the Medical University of Vienna . The work of this manuscript was supported via a research grant from the Danish Cancer Society (grant number R146-A9459-16-S2 ).
Funding Information:
Disclosures: A.V. and K.T. report grants from the Danish Cancer Society during the conduct of the study. K.T, M.Sc., and A.S. report grants from Elekta AB and Varian Medical Systems during the conduct of the study. S.S. and N.J. report grants from the Danish Cancer Society outside the submitted work. N.J. reports grants from the Danish Cancer Research Foundation outside the submitted work. J.L., R.N and R.P. report grants from Varian Medical Systems outside the submitted work. R.N., R.P., and M.Sc. report grants from Elekta AB outside the submitted work. R.N. reports grants from Accuray outside the submitted work. M.Sc. reports personal fees and nonfinancial support from Elekta AB outside the submitted work. A.S. reports grants from Stiftung Philanthropie Österreich, grants from Rosch, and personal fees from Elekta outside the submitted work.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - carcinoma
KW - chemoradiation
KW - clinical-trials
KW - european-organization
KW - gastrointestinal symptoms
KW - incontinence
KW - pelvic radiotherapy
KW - quality-of-life
KW - radiation-therapy
KW - recommendations
KW - PELVIC RADIOTHERAPY
KW - RADIATION-THERAPY
KW - GASTROINTESTINAL SYMPTOMS
KW - RECOMMENDATIONS
KW - INCONTINENCE
KW - CLINICAL-TRIALS
KW - CHEMORADIATION
KW - QUALITY-OF-LIFE
KW - EUROPEAN-ORGANIZATION
KW - CARCINOMA
U2 - 10.1016/j.ijrobp.2020.08.044
DO - 10.1016/j.ijrobp.2020.08.044
M3 - Article
C2 - 32853710
SN - 0360-3016
VL - 109
SP - 161
EP - 173
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -