Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

High fibrinogen levels are associated with poor survival in patients with liposarcoma.

The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan-Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10 mg/dL increase: 1.04; 95% CI 1.02-1.06; p < 0.001). This association prevailed in multivariable analysis after adjustment for AJCC tumor stage (HR 1.03; 95% CI 1.01-1.05; p = 0.013). Increasing levels of fibrinogen, a routinely available and inexpensive parameter, predicts the risk of mortality in patients with liposarcoma.

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.

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.

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.

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.

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.

Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients.

PURPOSE: The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144 Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70 Gy in 82 patients and 74 Gy in 170 patients. bNED rates (Phoenix definition) were assessed. RESULTS: The median follow-up was 46 months (range 1-148 months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002)-84% for patients receiving 70 Gy and 91% for patients receiving 74 Gy, respectively. In the univariate analysis, patients receiving 70 Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74 Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70 Gy EBRT showed significantly worse bNED rates compared to BT patients. CONCLUSION: Low-risk prostate cancer patients receiving 74 Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70 Gy show significantly worse outcome.