Image-guided adaptive brachytherapy (IGABT) for primary vaginal cancer: results of the international multicenter RetroEMBRAVE cohort study.

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Impact of interfractional target motion in locally advanced cervical cancer patients treated with spot scanning proton therapy using an internal target volume strategy

Background and purpose: The more localized dose deposition of proton therapy (PT) compared to photon therapy might allow a reduction in treatment-related side effects but induces additional challenges to address. The aim of this study was to evaluate the impact of interfractional motion on the target and organs at risk (OARs) in cervical cancer patients treated with spot scanning PT using an internal target volume (ITV) strategy. Methods and materials: For ten locally advanced cervical cancer patients, empty and full bladder planning computed tomography (pCT) as well as 25 daily cone beam CTs (CBCTs) were available. The Clinical Target Volume (CTV), the High Risk CTV (CTVHR) (gross tumor volume and whole cervix), the non-involved uterus as well as the OARs (bowel, bladder and rectum) were contoured on the daily CBCTs and transferred to the pCT through rigid bony match. Using synthetic CTs derived from pCTs, four-beam spot scanning PT plans were generated to target the patient-specific ITV with 45 Gy(RBE) in 25 fractions. This structure was defined based on pre-treatment MRI and CT to anticipate potential target motion throughout the treatment. D98% of the targets and V40Gy(RBE) of the OARs were extracted from the daily anatomies, accumulated and analyzed. In addition, the impact of bladder volume deviations from planning values on target and bowel dose was investigated. Results: The ITV strategy ensured a total accumulated dose >42.75 Gy(RBE) to the CTVHR for all ten patients. Two patients with large bladder-related uterus motion had accumulated dose to the non-involved uterus of 35.7 Gy(RBE) and 41.1 Gy(RBE). Variations in bowel V40Gy(RBE) were found to be correlated (Pearson r = −0.55; p-value <0.0001) with changes in bladder volume during treatment. Conclusion: The ITV concept ensured adequate dose to the CTVHR, but was insufficient for the non-involved uterus of patients subject to large target interfractional motion. CBCT monitoring and occasional replanning is recommended along the same lines as with photon radiotherapy in cervical cancer

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

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

Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future

Purpose: The purpose was to evaluate patient-and treatment-related risk factors for physician-assessed and patient-reported gastrointestinal (GI) symptoms after radio(chemo)therapy and image guided adaptive brachytherapy in locally advanced cervical cancer.Methods and Materials: Of 1416 patients from the EMBRACE-I study, 1199 and 1002 were prospectively evaluated using physician-assessed (Common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported (European Organization for Research and Treatment of Cancer [EORTC]) GI symptoms, respectively. CTCAE severe grade (grade [G] >3) events were pooled according to the location in the GI tract (anus/rectum, sigmoid, and colon/small bowel). CTCAE G >2 and EORTC "very much" and "quite a bit" plus "very much" scores (> "quite a bit") were analyzed for individual symptoms with Cox regression. Logistic regression was used for persistent G >1 and EORTC > "quite a bit" symptoms, defined if present in at least half of follow-ups.Results: The incidence of G >3 events was 2.8%, 1.8%, and 2.3% for G >3 anus/rectum, sigmoid, and colon/small bowel events, respectively. Among G >2 symptoms, diarrhea and flatulence were the most prevalent (8.5% and 9.9%, respectively). Among patient-related factors, baseline morbidity, increasing age, smoking status, and low body mass index were associated with GI symptoms to varying degrees. Among treatment-related factors, rectum D-2cm3 and the International Commission on Radiation Units and Measurements recto-vaginal reference point (ICRU RV-RP) correlated with G >3 anus/rectum events and moderate/persistent diarrhea, proctitis, bleeding, abdominal cramps, and difficulty in bowel control. Bowel D-2cm3 correlated with G >3 sigmoid and colon/small bowel events and moderate/persistent diarrhea and flatulence. For external beam radiation therapy (EBRT), prescription dose correlated with G >3 anus/rectum, diarrhea, and difficulty in bowel control. Patients with large lymph-node boost (V57Gy) were at higher risk for G >3 sigmoid events, moderate/persistent diarrhea, proctitis, and cramps.Conclusions: The analysis showed that both EBRT and image guided adaptive brachytherapy contribute to GI symptoms after locally advanced cervical cancer treatment. Rectum D-2cm3, ICRU RV-RP , and bowel D2cm3 are risk factors for GI morbidity. The risk for various symptoms was lower with an EBRT prescription of 45 Gy than 50 Gy and increased with larger V57Gy. (C) 2021 Elsevier Inc. All rights reserved