Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy.

OBJECTIVE: The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer. METHODS: Eligible patients had stage IB1-IIIB cervical cancer with ≤5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual questionnaires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coefficients. RESULTS: 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vaginal changes and PRO sexual satisfaction differed significantly (p ≤ .05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found. CONCLUSIONS: Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachytherapy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone.

Impact of transitioning to an online course - A report from the ESTRO gyn teaching course.

INTRODUCTION: In 2020, the ESTRO course on image-guided radiotherapy and chemotherapy in gynaecological cancer was converted into an online version due to the COVID-19 pandemic. This paper describes the change process and evaluates the impact on participants compared with previous live courses. METHODS AND MATERIALS: The 2019 live course contained 41 h of educational content, comprising 33 h of synchronous activities (lectures, interactive activities, videos) and 8 h of homework (contouring, dose planning). For the online course, the lectures were provided as pre-course material (11 mandatory, 22 optional). Contouring/dose planning homework was unchanged. The synchronous sessions were reconfigured as six 2-hour webinars (total educational content ~38 h).Participant numbers/characteristics, engagement and satisfaction for six live courses and the online course were compared. RESULTS: Participant numbers for the online and live courses were similar (90 vs. mean 96). There were more participants from outside Europe (28% vs. mean 18%) and more non-doctors (47% vs. mean 33%). Proportion of participants responding to the pre-course questionnaire was similar (77% vs. mean 78%) but post-course questionnaire response was lower (62% vs. mean 92%).43% participants viewed ≥75% of mandatory lectures before the webinars. 86% viewed the optional lectures. Submissions of contouring and dose planning homework was higher (contouring 77%-90% vs. 56%-69%, dose planning 74%-89% vs. 29%-57%).96% (47/49) participants rated the online course as Excellent (43%) or Good (53%). Overall satisfaction was similar (4.4 vs. mean 4.6). CONCLUSION: Participant satisfaction and engagement with the online course remained high despite less contact time with faculty.

Reliability of stemless shoulder arthroplasty in rheumatoid arthritis: observation of early lysis around the humeral component.

PURPOSE: To evaluate whether stemless shoulder implants in rheumatoid arthritis (RA) patients provide comparable functional outcomes to patients with osteoarthritis or post-traumatic arthritis. In addition, the study assessed for differences in incidence of radiolucent lines or proximal humeral bone loss during radiographic follow-up. METHODS: Consecutive stemless shoulder arthroplasties performed in RA patients and a matched control group were retrospectively identified between February 2012 and 2018. Thirty-five patients were included in each group: 24 total shoulder arthroplasty (TSA) and 11 hemiarthroplasty (HA). Patients were evaluated annually using the Oxford Shoulder Score (OSS) and radiographically. RESULTS: The mean OSS significantly improved in all groups until 24 months. The mean improvement for RA TSA and HA patients at 24 months was 19.86 (95% CI 10.66-29.05, p = 0.0004) and 19.71 (95% CI 7.33-32.31, p = 0.0084), respectively. The mean improvement in the control TSA and HA patients at 24 months was 20.86 (95% CI 17-24.71, p = 0.0001) and 17.86 (95% CI 1.36-34.35, p = 0.0381), respectively. During the study period, two patients in the RA TSA group (8%), one patient in the control TSA group (4%) and one patient in the control HA group (9%) required revision. The proportion of progressive proximal humeral bone loss after TSA was 33% in the RA group and 13% in the control group. CONCLUSION: Stemless shoulder implants can provide significant improvement in functional scores in RA patients in the short term. However, early bone loss around the humeral implant is a concern and the authors recommend long-term clinical and radiological follow-up.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Assessment of dose to functional sub-structures in the lower urinary tract in locally advanced cervical cancer radiotherapy.

PURPOSE: To provide an analysis of dose distribution in sub-structures that could be responsible for urinary toxicity after Image-Guided Adaptive BrachyTherapy (IGABT) in Locally Advanced Cervical Cancer (LACC). METHODS: 105 LACC patients treated with radiochemotherapy and IGABT were selected. Sub-structures (bladder wall, trigone, bladder neck, urethra) were contoured on IGABT-planning MRIs. D2cm3 and D0.1cm3, ICRU Bladder-Point (ICRU BP) and Posterior-Inferior Border of Symphysis points (PIBS, PIBS + 2 cm, PIBS - 2 cm) doses were extracted. Internal-Urethral-Ostium (IUO) and PIBS-Urethra (PIBS-U) points were defined as urethral dose surrogates. Finally, the Vaginal Reference Length (VRL) was extracted. Values were converted into total EBRT + BT equivalent dose in 2 Gy fractions using α/ß = 3 and T1/2 = 1.5 h. RESULTS: Median D2cm3 for bladder and trigone were 71.7[interquartile-range:66.5;74.1]Gy and 57.8[53.3;63.6]Gy, respectively, while median D0.1cm3 were 82.2[77.6;89.1]Gy and 70.7[62.0;76.7]Gy, respectively. Median ICRU BP dose was 63.7[56.5;70.5]Gy and correlated with trigone D2cm3 and D0.1cm3, while bladder and trigone D2cm3 had poor correlation (R2 = 0.492), as well as D0.1cm3 (R2 = 0.356). Bladder neck D0.1cm3 was always lower than trigone D0.1cm3 and higher than IUO. Correlation between PIBS + 2 cm and IUO was poor (R2 = 0.273), while PIBS and PIBS-U were almost equal (R2 = 0.990). VRL correlated with dose to bladder base. CONCLUSIONS: The study confirmed that ICRU BP and trigone doses correlate. Bladder D2cm3 is not representative of trigone dose because hotspots are often placed in the bladder dome. VRL is a good indicator for bladder base sparing. In addition to D2cm3 and D0.1cm3 for whole bladder, ICRU BP, trigone D2cm3 and D0.1cm3, IUO and PIBS are useful for lower urinary tract reporting.

Concepts and terms for dose/volume parameters in carbon-ion radiotherapy: Conclusions of the ULICE taskforce.

PURPOSE: The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. METHODS AND MATERIALS: The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. RESULTS: Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. CONCLUSIONS: This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile).

Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy.

OBJECTIVE: The aim of this study is to investigate patterns of distant relapse after primary radiochemotherapy in cervical cancer patients. METHODS: All patients with cervical cancer treated in curative intent with external beam radiotherapy +/- chemotherapy and image-guided adaptive brachytherapy between January 1998 and June 2009 at the Medical University of Vienna were included in this retrospective analysis. Patients with locoregional recurrences were excluded from this study. Presence, site of and time to distant metastases were recorded. For identifying prognostic factors, uni- and multivariate analyses using Cox regression analysis were performed. Based on the result from the multivariate analysis, patients were stratified into a high and a low risk group. The Kaplan-Meier method was used to estimate distant-metastasis-free-survival in the overall cohort, in the risk groups and for analysing the impact of chemotherapy within the risk groups. RESULTS: A total number of 189 patients were included in this study. After a median follow-up of 54 months, 49 patients developed distant metastases. Overall, distant-metastasis-free-survival 5 years after treatment was 73%. FIGO stage, lymph node status and the extent of tumour regression during treatment were significant predictors for distant metastasis. Distant-metastasis-free-survival 5 years after treatment was 91% and 60% in the low and high risk groups, respectively. The number of the cycles of chemotherapy had a significant impact on the occurrence of distant metastasis in high risk patients, but not in low risk patients. CONCLUSION: Patients with high risk factors have a 40% probability of developing distant metastasis within 5 years. In these patients, decreasing the number of cycles of cisplatin may increase their probability of developing distant metastasis.

Validation and practical implementation of a multidisciplinary cancer distress screening questionnaire.

BACKGROUND: In order to identify cancer patients with psychosocial needs during radiotherapy, a routine screening questionnaire is widely recommended in the literature. Several tools focusing mainly on psychological issues have been developed during the past decade. However, problems with their implementation into clinical routine have been repeatedly reported, due to a lack of practicability for clinicians and nurses. This study reports the compilation of a multidisciplinary screening questionnaire and an analysis of the effectiveness of its implementation into clinical routine at the Department of Radiotherapy, Medical University of Vienna. MATERIALS AND METHODS: The screening questionnaire is based on a compilation of several subscales from established and validated assessment tools. It focuses on comprehensive information with high a clinical relevance for all professions. In a pilot study, patients' acceptance was assessed qualitatively. Analysis of missing screening data in consecutively admitted patients reflects the effectiveness of implementation and representativity of the data. A validation analysis of the psychological subscales was performed using external criteria and its internal consistency was tested with Cronbachs' α. RESULTS: Qualitative patient acceptance of the screening questionnaire is good. The overall response rate in the screening procedure was 75 %. Missing patient screening data sets arose randomly-mainly due to organizational problems-and did not result in systematic errors. The psychological subscales identify highly distressed patients with a sensitivity of 89 and 78 %, and an internal consistency of 0.843 and 0.617. CONCLUSION: The multidisciplinary screening questionnaire compiled in this study has a high patient acceptance, provides reliable and representative data and identifies highly distressed patients with excellent sensitivity. Although requiring additional personnel resources, it can be implemented successfully in clinical routine with benefits for both the patient and the professional team.

Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. PATIENTS AND METHODS: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue--Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). RESULTS: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. CONCLUSION: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information.

Physical and psychosocial support requirements of 1,500 patients starting radiotherapy.

BACKGROUND: The need for psychosocial support in cancer patients is estimated in the literature at 14-50 %. At the Department of Radiation Oncology, Medical University of Vienna, approximately 3,000 patients are seen annually. Due to limited staff resources, highly distressed patients need to be selected for focused support. A multidisciplinary screening questionnaire covering physical, social and psychological problems and needs was successfully implemented in clinical routine. We present the results of a representative sample of 1,500 heterogeneous cancer patients before beginning radiotherapy. PATIENTS AND METHODS: The prevalence rates of physical, social and psychological problems and needs were evaluated. Independent risk factors for critical psychological distress were analyzed in a multivariate logistic regression model, in order to identify vulnerable subgroups for focused psychosocial support. RESULTS: Critical psychological distress was found in 22 % of the overall cohort, of whom only 26 % reported a need for psychological information. Clinically relevant pain was suffered by 31 %. Patients' most frequent complaints were weakness, sleeping difficulties and exhaustion. Consequently, 40 % were impaired in activities and 35 % reported a requirement for support in daily life. A need for further information was expressed by 37 % of patients. Significant risk factors for critical psychological distress included pain, functional status, support requirements and patient-reported symptoms. Differences in tumor type, metastases and sociodemographic variables had no impact on critical psychological distress. CONCLUSION: Approximately one third of all patients beginning radiotherapy have physical, social and psychological problems and should receive focused psychosocial support. Multivariate analysis reveals that patients with impaired "physical integrity" are at a significantly higher risk of experiencing critical psychological distress.

Residual tumour volumes and grey zones after external beam radiotherapy (with or without chemotherapy) in cervical cancer patients. A low-field MRI study.

BACKGROUND: Grey zones, which are defined as tissue with intermediate signal intensity in the area of primary hyperintense tumour extension, can be seen during radiation with or without chemotherapy on the T2-weighted MRI in patients with cervical cancer. The purpose of this study was to systematically measure the tumour volume at the time of diagnosis and the residual tumour volume at the time of brachytherapy without and with consideration of the grey zones and to estimate tumour regression during external beam radiotherapy (EBRT). MATERIAL AND METHODS: T2-weighted MRI datasets of 175 patients with locally advanced cervical cancer (FIGO stage IB-IVA), who underwent combined external beam radiotherapy and brachytherapy with or without concomitant chemotherapy were available for this study. The gross tumour volume at the time of diagnosis (GTV(init)) and at the time of first brachytherapy without (GTV(res)) and with (GTV(res)+ GZ) consideration of grey zones were measured for each patient. A descriptive statistical analysis was performed and tumour regression rates without (R) and with consideration of grey zones (R(GZ)) were calculated. Further, the role of prognostic factors on GTV(init), GTV(res), GTV(res)+ GZ and tumour regression rates was investigated. RESULTS: The median GTV(init), GTV(res), GTV(res)+ GZ in all patients were 44.4 cm(3), 8.2 cm(3), 20.3 cm(3), respectively. The median R was 78.5% and the median R(GZ) was 50.1%. The histology and FIGO staging showed a significant impact on GTV(init), GTV(res) and GTV(res)+ GZ. CONCLUSION: Grey zones represent a substantial proportion of the residual tumour volume at the time of brachytherapy. Differentiation of high signal intensity mass and surrounding intermediate signal intensity grey zones may be reasonable.

Can treatment of pediatric Hodgkin's lymphoma be improved by PET imaging and proton therapy?

BACKGROUND AND PURPOSE: To explore a new positron emission tomography (PET)-based target concept for pediatric Hodgkin's lymphoma (PHL). PATIENTS AND METHODS: For 10 patients, the planning target volume PTV1 was based on initial CT tumor extension and PTV2 on anatomy-related PET-positive lymph node levels after chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy) comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field (PS) proton techniques. Treatment concepts were compared concerning dose-volume histogram (DVH) parameters and organ-equivalent doses (OED). RESULTS: The median PTV1 and PTV2 were 902 ± 555 cm(3) and 281 ± 228 cm(3). When using PTV2 instead of PTV1 for all techniques, the D(2%) of the heart was reduced from 14 to 9 Gy and the D(mean) of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median- (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to 60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54 ± 10% for all organs at risk. CONCLUSION: PTV2 has a high impact on the treated volume and on sparing of organs at risk. The combination of an adaptive target volume definition with protons could contribute to future PHL treatment concepts.

Feasibility of transrectal ultrasonography for assessment of cervical cancer.

PURPOSE: To retrospectively compare the maximum target width and target thickness in patients with locally advanced cervical cancer between magnetic resonance imaging (MRI) and transrectal ultrasonography (TRUS) in the course of primary radiochemotherapy. PATIENTS AND METHODS: T2-weighted MRI and TRUS were performed on patients with locally advanced cervical cancer at the same timepoint-either at the time of diagnosis, or at the time of brachytherapy before or after insertion of the applicator. Patients treated from 2009 to 2011 were selected for this study based on the availability of MRI and TRUS at the defined time points. The target was defined as the complete macroscopic tumor mass and the remaining cervix and was measured on transversal planes. Descriptive statistics and a linear regression analysis were performed for the groups. RESULTS: Images from 17 patients were available for analysis. Mean maximum target width was 4.2 ± 0.83 cm and 4.2 ± 0.79 cm for MRI and TRUS, respectively. Mean maximum target thickness was 3.3 ± 1.03 cm and 3.1 ± 1.15 cm for MRI and TRUS, respectively. Linear regression analysis for target width and thickness between TRUS and MRI demonstrated a correlation with R(2) = 0.842 and R(2) = 0.943, respectively. CONCLUSION: The feasibility of TRUS for the assessment of local target extension could be demonstrated. Comparison of the target width and thickness showed a high correlation between TRUS and MRI, indicating the potential of TRUS for target definition in image-guided adaptive brachytherapy.

Multicenter evaluation of different target volume delineation concepts in pediatric Hodgkin's lymphoma. A case study.

BACKGROUND AND PURPOSE: In pediatric Hodgkin's lymphoma (PHL) improvements in imaging and multiagent chemotherapy have allowed for a reduction in target volume. The involved-node (IN) concept is being tested in several treatment regimens for adult Hodgkin's lymphoma. So far there is no consensus on the definition of the IN. To improve the reproducibility of the IN, we tested a new involved-node-level (INL) concept, using defined anatomical boundaries as basis for target delineation. The aim was to evaluate the feasibility of IN and INL concepts for PHL in terms of interobserver variability. PATIENTS AND METHODS: The INL concept was defined for the neck and mediastinum by the PHL Radiotherapy Group based on accepted concepts for solid tumors. Seven radiation oncologists from six European centers contoured neck and mediastinal clinical target volumes (CTVs) of 2 patients according to the IN and the new INL concepts. The median CTVs, coefficient of variation (COV), and general conformity index (CI) were assessed. The intraclass correlation coefficient (ICC) for reliability of delineations was calculated. RESULTS: All observers agreed that INL is a feasible and practicable delineation concept resulting in stronger interobserver concordance than the IN (mediastinum CI(INL) = 0.39 vs. CI(IN) = 0.28, neck left CI(INL) = 0.33; CI(IN) = 0.18; neck right CI(INL) = 0.24, CI(IN) = 0.14). The COV showed less dispersion and the ICC indicated higher reliability of contouring for INL (ICC(INL) = 0.62, p < 0.05) as for IN (ICC(IN) = 0.40, p < 0.05). CONCLUSION: INL is a practical and feasible alternative to IN resulting in more homogeneous target delineation, and it should be therefore considered as a future target volume concept in PHL.

Radiation-induced morphological changes in the vagina.

BACKGROUND AND PURPOSE: Treatment-induced chronic vaginal changes after definitive radio(chemo)therapy for locally advanced cervical cancer patients are reported as one of the most distressing consequences of treatment, with major impact on quality of life. Although these vaginal changes are regularly documented during gynecological follow-up examinations, the classic radiation morbidity grading scales are not concise in their reporting. The aim of the study was therefore to identify and qualitatively describe, on the basis of vaginoscopies, morphological changes in the vagina after definitive radio(chemo)therapy and to establish a classification system for their detailed and reproducible documentation. PATIENTS AND METHODS: Vaginoscopy with photodocumentation was performed prospectively in 22 patients with locally advanced cervical cancer after definitive radio(chemo)therapy at 3-24 months after end of treatment. All patients were in complete remission and without severe grade 3/4 morbidity outside the vagina. RESULTS: Five morphological parameters, which occurred consistently after treatment, were identified: mucosal pallor, telangiectasia, fragility of the vaginal wall, ulceration, and adhesions/occlusion. The symptoms in general were observed at different time points in individual patients; their quality was independent of the time of assessment. Based on the morphological findings, a comprehensive descriptive and semiquantitative scoring system was developed, which allows for classification of vaginal changes. A photographic atlas to illustrate the morphology of the alterations is presented. CONCLUSION: Vaginoscopy is an easily applicable, informative, and well-tolerated procedure for the objective assessment of morphological vaginal changes after radio(chemo)therapy and provides comprehensive and detailed information. This allows for precise classification of the severity of individual changes.