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Pelvic lymph node dissection (PLND) is part of the primary treatment for early–stage cervical cancer and high–intermediate risk or high–risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND, and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot–assisted laparoscopic PLND in cervical and endometrial cancer. Retrospective cohort study. Single–center academic hospital. Two hundred and fifty–eight patients with cervical cancer and 129 patients with endometrial cancer. Pelvic lymphadenectomy by robot–assisted laparoscopic surgery. The authors retrospectively included all patients with early–stage cervical cancer and high–intermediate risk or high–risk endometrial cancer who underwent pelvic lymphadenectomy by robot–assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total, 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow–up of 47 months [interquartile range 23–61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19–5.11) and multivariate analysis (OR 2.42, 95% CI 1.16–5.07). For cervical cancer, body mass index (BMI) (OR 1.09, 95% CI 1.00–1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22–6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as a significant independent risk factor (OR 0.90, 95% CI 0.83–0.97). This single–center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot–assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the 2 populations, necessitating further studies to establish risk models. [ABSTRACT FROM AUTHOR]

• Vacuum cushion immobilization reduced intrafraction motion in posterior direction. • Most intrafraction motion occurred in the first 16 minutes. • On an MR-linac, vacuum cushion immobilization may not be needed for single targets. Vacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion. Thirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction. Vacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p < 0.05). Mean GTV intrafraction motion reduction in posterior direction was 0.7 mm (95% confidence interval 0.3–1.1 mm) for pre-post interval (mean time = 32 min). Shifts in other directions were not significantly reduced. More motion occurred in pre-PV interval than in PV-post interval (mean time = 16 min for both); vacuum cushion immobilization did not reduce intrafraction motion during the beam-on period. A vacuum cushion reduces GTV and bony anatomy intrafraction motion in posterior direction during pelvic/para-aortic lymph node SBRT. This motion reduction was found for the first 16 min per session. For single targets this motion can be corrected for directly with an MR-linac. Intrafraction motion was not reduced during the second half of the session, the period of radiotherapy delivery on an MR-linac. Vacuum cushion immobilization may not be necessary for patients with single lymph node oligometastases undergoing SBRT on an MR-linac. [ABSTRACT FROM AUTHOR]

The last 2 decades have witnessed the development and broad adoption of image-guided adaptive brachytherapy (IGABT) combined with radiochemotherapy in patients with locally advanced cervical cancer. A variety of brachytherapy techniques and dose/fractionation schedules have been applied, and until recently, there was no strong evidence available for preferring one approach to another. However, large volumes of data have now provided high level clinical evidence for dose-effect relations for both disease and morbidity endpoints. It is therefore now possible to apply evidence based dose planning aims and dose prescription protocols in IGABT for locally advanced cervical cancer. This review gives an overview of targets/organs-at-risk and disease/morbidity endpoints which are relevant in the context of treatment planning and dose prescription in IGABT. The dosimetric and clinical evidence is summarized to support the implementation of dose prescription protocols which include hard and soft constraints for targets and organs at risk. [ABSTRACT FROM AUTHOR]

During the last decade the adoption of image-guided adaptive brachytherapy has dramatically improved local control in patients with locally advanced cervical cancer (LACC) treated with radiotherapy and concomitant chemotherapy; however, nodal failure remains an obstacle. Metastatic lymph nodes can be detected by surgical and imaging approaches with different sensitivities and specificities, that improve the definition of relevant targets for macroscopic and microscopic nodal disease, and that influence our understanding of dose levels of external beam radiotherapy. Systematic use of modern radiotherapy techniques including intensity modulated radiotherapy and simultaneously integrated nodal boosts in combination with daily position verification is emerging as increasingly important for obtaining nodal control in LACC. This review summarizes published and ongoing efforts for optimizing nodal disease treatment in LACC, elaborates the state of the art approach for nodal disease detection, radiotherapy planning and delivery, and discusses future investigational efforts needed for precise optimization. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV–PTV margins. We also studied their correlation with surrounding organ filling. Materials and methods: Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage. Results: The vaginal CTVs change their position in the pelvis during time with a maximum in anterior–posterior direction. The 95% confidence level was 2.3cm into the anterior or posterior direction, 1.8cm to left or right and 1.5cm towards the cranial. With a homogenous 1.5cm CTV–PTV margin ⩾5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior–posterior. Conclusion: To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior–posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder. [Copyright &y& Elsevier]

Abstract: Purpose: To perform a qualitative and quantitative comparison of different treatment planning methods used in different centres for MRI-based brachytherapy (BT) of cervical cancer. Materials and methods: Two representative patients with advanced cervical cancer (1 “limited volume case”; 1 “extensive volume case”) were planned for brachytherapy (BT) with a tandem-ring applicator by six different centres. During a workshop all centres produced an institutional standard plan and an MRI-based adaptive treatment plan for each case. Optimisation was based on the fractionation schedule (HDR, PDR) and method according to the institutional protocol. Results: The loading pattern, dwell times, shape of the point A isodose varied considerably between institutional standard plans, as did dose–volume parameters for high risk CTV (HR-CTV) and also for the D2cc for OAR, violating the dose–volume constraints in many situations. During optimisation, the centres stayed as close as possible to the standard loading pattern and dwell times. The dose distributions and dose–volume parameters between the plans from the different centres became much more comparable after optimisation. The prescribed dose to the HR-CTV could be achieved in the limited volume case by all centres, in the extensive case only if additional needles were applied. Conclusion: Treatment planning for gynaecologic brachytherapy based on different traditions shows less variation in regard to target coverage and OAR dose, when 3D image-based optimisation is performed with a uniform prescription protocol. [Copyright &y& Elsevier]

Abstract: Purpose: To study the impact of MRI-guided treatment planning on dose/volume parameters in pulsed dose rate (PDR) brachytherapy (BT) for cervical cancer. Additionally, we investigated the potential benefit of an intracavitary/interstitial (IC/IS) modification of the classical tandem ovoid applicator. Material and methods: For 24 patients we compared Standard PDR BT plans, Scaled Standard plans and MRI-guided Optimised plans. The total EBRT/BT prescribed dose to Manchester point A or to 90% of the HR-CTV (D90 HR-CTV) expressed in EQD2 was 80Gyαβ10 in 17 patients (Period I) and 84Gyαβ10 in 7 patients (Period II). The constraints to 2 cm3 of the OAR were 90Gyαβ3 for bladder and 75Gyαβ3 for rectum, sigmoid and bowel. Most cases were treated with a traditional intracavitary tandem ovoid applicator. In 6 patients we used a newly designed combined IC/IS modification for the second PDR fraction and investigated the benefit of the interstitial part. Results: The average gain of MRI-guided optimisation expressed in D90 HR-CTV was 4±9Gyαβ10 (p <0.001) and 10±7Gyαβ10 (p =0.003) in the two periods. The dose to 2 cm3 of the OAR met the constraints. In the group that was treated with the combined IC/IS approach, we could increase the D90 HR-CTV for the second PDR fraction with 5.4±4.2Gyαβ10 (p =0.005) and the D100 with 4.8±3.1Gyαβ10 (p =0.07). Conclusions: Three-dimensional MRI-guided treatment planning and optimisation improves the DVH parameters compared to conventional planning strategies. Additional improvement can be achieved by using a combined IC/IS approach. [Copyright &y& Elsevier]

Abstract: Background and Purpose: For cervical cancer patients the CTV consists of multiple structures, exhibiting complex inter-fraction changes. The purpose of this study is to use weekly MR imaging to derive PTV margins that accommodate these changes. Materials and methods: Twenty patients with cervical cancer underwent a T2-weighted MRI exam before and weekly during IMRT. The CTV, GTV and surrounding organs were delineated. PTV margins were derived from the boundaries of the GTV and CTV in the six main directions and correlated with changes in the volumes of organs at risk. Results: Around the GTV a margin of 12, 14, 12, 11, 4 and 8mm to the anterior, posterior, right lateral, left lateral, superior and inferior directions was needed. The CTV required margins of 24, 17, 12, 16, 11 and 8mm. The shift of the GTV and CTV in the AP directions correlated weakly with the change in rectal volume. For the bladder the correlations were even weaker. Conclusions: We used weekly MRI scans to derive inhomogeneous PTV margins that accommodate changes in GTV and CTV. The weak correlations with rectum and bladder volume suggest that measures to control filling status of these organs may not be very effective. [Copyright &y& Elsevier]

Purpose: To affirm the effectiveness and complication rate of postoperative single-dose β-irradiation (RT) with 90Sr in the case of primary pterygium in a clinical trial. Pterygium is a benign disease of the supporting orbital tissue that can cause impairment of visual function. Depending on the technique used for surgery, recurrence is described in up to 70% of cases—a reason to combine the initial treatment with radiotherapy or chemotherapy.Methods and materials: This trial was designed as a prospective, randomized, multicenter, double-blind study. Surgery was performed in all cases according to the bare sclera technique. Ninety-one patients with 96 pterygia were postoperatively randomized to either β-RT or sham RT. In the case of β-RT, a 90Sr eye applicator was used to deliver 2500 cGy to the sclera surface at a dose rate of between 200 and 250 cGy/min. Sham RT was given using the same type of applicator without the 90Sr layer. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test.Results: Between February 1998 and September 2002, 96 eyes with primary pterygium were operated on according to the trial protocol. Additional treatment was performed within 24 hours postoperatively. Ten patients were lost to follow-up, resulting in 86 patients who could be analyzed. In the 44 eyes randomized to receive β-RT, 3 relapses occurred compared with 28 recurrences in the 42 eyes that received sham RT, for a crude control rate of 93.2% vs. 33.3%, respectively. At a mean follow-up of 18 months, major treatment complications had not been observed.Conclusion: Single-dose β-RT after bare sclera surgery is a simple, effective, and safe treatment that reduces the risk of primary pterygium recurrence. [Copyright &y& Elsevier]

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study.Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ2).Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = -0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062).Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials. In this multimethod analysis, data from 1801 women participating in the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials were used for statistical analyses and causal inference. The cohort included 714 patients with intermediate-risk endometrial cancer, 427 patients with high-intermediate risk endometrial cancer, and 660 patients with high-risk endometrial cancer. Associations of age with clinicopathological and molecular features were analysed using non-parametric tests. Multivariable competing risk analyses were performed to determine the independent prognostic value of age. To analyse age as a causal prognostic variable, a deep learning causal inference model called AutoCI was used. Median follow-up as estimated using the reversed Kaplan-Meier method was 12·3 years (95% CI 11·9–12·6) for PORTEC-1, 10·5 years (10·2–10·7) for PORTEC-2, and 6·1 years (5·9–6·3) for PORTEC-3. Both overall recurrence and endometrial cancer-specific death significantly increased with age. Moreover, older women had a higher frequency of deep myometrial invasion, serous tumour histology, and p53-abnormal tumours. Age was an independent risk factor for both overall recurrence (hazard ratio [HR] 1·02 per year, 95% CI 1·01–1·04; p=0·0012) and endometrial cancer-specific death (HR 1·03 per year, 1·01–1·05; p=0·0012) and was identified as a significant causal variable. This study showed that advanced age was associated with more aggressive tumour features in women with endometrial cancer, and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone. None. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to assess variability in contouring the gross tumor volume (GTV) and clinical target volume (CTV) of 3 clinical cervix cancer cases by a cohort of international experts in the field in preparation for the development of an online teaching atlas. Methods and materials Twelve international experts participated. Three clinical scenarios: node positivity (PLN), retroverted uterus (RV), and parametrial invasion (PI) were used. Sagittal and axial magnetic resonance images of the clinical cases were downloaded to participants’ treatment planning systems for contouring. The GTV/cervix/uterus/parametria/vagina and nodal CTV were contoured. Contour consensus was assessed for sensitivity/specificity using an expectation maximization algorithm called Simultaneous Truth and Performance Level Estimation and experts’ overall agreement was summarized by kappa statistics. Results Agreement for GTV in the 3 clinical cases was high (Simultaneous Truth and Performance Level Estimation sensitivity, 0.54-0.92; specificity, 0.97-0.98; and kappa measure for PLN, RV, and PI was 0.86, 0.76, and 0.42; P < .0001). Moderate to substantial agreement was seen for nodal CTV (kappa statistics for PLN, RV, and PI was 0.65, 0.58, and 0.62; P < .0001), uterus (kappa for PLN, RV, and PI was 0.45, 0.74, and 0.77; P < .0001), and parametria (kappa for PLN, RV, and PI was 0.49, 0.62, and 0.50; P < .0001). Contouring heterogeneity was greatest for the cervix (kappa measure for PLN, RV, and PI was 0.15, 0.4, and 0.24; P < .0001) and vagina (kappa for PLN, RV, and PI was 0.47, 0.36 and 0.46; P < .0001), reflecting difficulties in determining the interface between GTV and these tissues. Conclusion Kappa statistics of the different CTV components generally demonstrated moderate to substantial agreement among international experts in the field of gynecological radiation therapy. Further planning target volume margins accounting for organ motion and setup errors are a necessary addition to the CTV. [ABSTRACT FROM AUTHOR]