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Background: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. Methods: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. Results: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. Discussion: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. Clinical trial registration: NCT03611517. [ABSTRACT FROM AUTHOR]

Purpose: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound. Methods: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline. Results: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10−3mm2/s increase 12 months after treatment (p = 0.15). Conclusion: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound. [ABSTRACT FROM AUTHOR]

Background: Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement. Methods: Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan–Meier method, log-rank tests and Cox's proportional hazard models were used for survival analysis. Results: In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15–0.75). Conclusions: We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment. [ABSTRACT FROM AUTHOR]

B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker. Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial. [ABSTRACT FROM AUTHOR]

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes the international, cross-cultural development of four disease-specific EORTC QoL questionnaires, to supplement the EORTC QLQ-C30, for patients with Hodgkin lymphoma (HL), high- or low-grade non-Hodgkin lymphoma (HG/LG-NHL), and CLL.Methods: Questionnaire development was conducted according to guidelines from the EORTC Quality of Life Group. Phase I comprised generation of QoL issues relevant to patients. Phase II included operationalization and assessment of item relevance. In phase III, items were pretested in a cross-cultural sample.Results: In Phase I, 75 issues were identified through focus groups and systematic literature searches. Interviews with 80 health-care professionals and 245 patients resulted in a provisional module of 38 items (phase II) representing items relevant for all or at least one of the four malignancies. In Phase III, this was tested in 337 patients from five European countries and resulted in a questionnaire with 27 items for HL (EORTC QLQ-HL27), 29 items for HG-NHL (EORTC QLQ-NHL-HG29), 20 items for LG-NHL (EORTC QLQ-NHL-LG20) and 17 items for CLL (EORTC QLQ-CLL17).Conclusions: This study provides four new EORTC modules for use in clinical research and routine practice in conjunction with the EORTC QLQ-C30 for assessing QoL in patients with lymphoma and CLL. [ABSTRACT FROM AUTHOR]

Background: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer.Methods: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%.Results: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences.Conclusions: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers. [ABSTRACT FROM AUTHOR]

Purpose: About half of the gynecological cancer (GC) survivors suffer from sexual dysfunctions and report a need for professional psychosexual support. The current study assessed (1) health care professionals' (HCP) current psychosexual support practices, (2) barriers to providing psychosexual support, and (3) HCP needs for training and assistance. Methods: Semistructured interviews were conducted with gynecological oncologists ( n = 10), radiation oncologists ( n = 10), and oncology nurses involved in the treatment of GC ( n = 10). Results: The majority of the professionals reported discussing sexuality at least once with each patient. An important reason for addressing sexual functioning was to reassure patients that it is normal to experience sexual concerns and give them an opportunity to discuss sexual issues. About half of the professionals provided specific suggestions. Patients were rarely referred to a sexologist. Barriers encountered by professionals in the provision of psychosexual support were embarrassment and lack of time. HCP suggestions for the facilitation of psychosexual support provision were skills training, an increased availability of patient information, and the standard integration of psychosexual support in total gynecological cancer care. Conclusion: The majority of the professionals reported discussing sexuality at least once with every patient, but discussions of sexual functioning were often limited by time and attention. The development of comprehensive patient information about sexuality after GC is recommended as well as a more standard integration of psychosexual support in GC care and specific training. [ABSTRACT FROM AUTHOR]

Hodgkin Lymphoma (HL) survivors are at risk for adverse psychosocial events as a result from cancer diagnosis and treatment. Fatigue is one of the most frequently reported long-term symptoms and is often reported to interfere with daily life. We conducted a systematic review to determine prevalence, severity and predisposing factors of fatigue in HL survivors. A literature search was conducted up to August 2012. Twenty-two articles comparing HL survivors with norm population data met all predefined selection criteria. Prevalence rates, levels of fatigue and clinical relevance of the results were determined. Prevalence of fatigue ranged from 11-76 % in HL survivors compared to 10 % in the general population. Mean fatigue scores were 5-13 % higher compared to the normative population; these findings were clinically relevant in 7 out of 11 studies. Increasing age was associated with higher levels of fatigue in HL survivors. Treatment modality and stage of initial disease were not associated with higher fatigue levels, while comorbidities or other treatment sequelae seemed to impact on the levels of fatigue. HL survivors are at serious risk for developing clinically relevant, long-term fatigue. The impact of patient and treatment characteristics on risk of fatigue is limited. Focus for future research should shift to the role of late-treatment sequelae and psychological distress symptoms. [ABSTRACT FROM AUTHOR]

To improve posttreatment care for (long-term) lymphoma survivors in the Netherlands, survivorship clinics are being developed. As information provision is an important aspect of survivorship care, our aim was to evaluate the current perceived level of and satisfaction with information received by non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) survivors, and to identify associations with sociodemographic and clinical characteristics. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with NHL, HL and MM from 1999 to 2009. In total, 1,448 survivors received a questionnaire, and 1,135 of them responded (78.4 %). The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information. Two thirds of survivors were satisfied with the amount of received information, with HL survivors being most satisfied (74 %). At least 25 % of survivors wanted more information. Young age, having had chemotherapy, having been diagnosed more recently, using internet for information and having no comorbidities were the most important factors associated with higher perceived levels of information provision. Although information provision and satisfaction with information seems relatively good in lymphoma and MM survivors, one third expressed unmet needs. Furthermore, variations between subgroups were observed. Good information provision is known to be associated with better quality of life. Survivorship care plans could be a way to achieve this. [ABSTRACT FROM AUTHOR]

Adjuvant treatment of patients with endometrial cancer is tailored to clinical-pathological prognostic factors. Pelvic radiation therapy for stage I endometrial cancer (EC) provides a highly significant improvement of local control, but without survival advantage. Low-risk EC patients have a very favorable prognosis, and should be observed after surgery. Use of adjuvant radiotherapy (RT) is limited to patients with high-intermediate or high-risk factors. For those with high-intermediate risk features, vaginal brachytherapy alone provides excellent vaginal control with less morbidity and better quality of life than pelvic external beam RT (EBRT). For patients with stage I-III EC with high-risk features, the use of adjuvant chemotherapy alone has not shown survival benefit as compared to pelvic EBRT. A first trial comparing pelvic EBRT with or without adjuvant chemotherapy has shown better progression-free survival with combined therapy. Current ongoing trials are exploring the role of combined RT and chemotherapy, compared to chemotherapy or RT alone. [ABSTRACT FROM AUTHOR]

Purpose of Review: To provide an overview of common molecular risk factors in endometrial cancer (EC) with the possibility to improve adjuvant treatment selection. Recent Findings: Recent studies have discovered and confirmed four different molecular subclasses in EC, with each having a distinct prognosis; POLE-ultramutated, microsatellite unstable, copy-number low, and copy-number high. Subsequent studies have shown that combining both molecular with clinicopathological risk factors can potentially improve adjuvant treatment selection for women with high-intermediate risk EC. For high risk and advanced stage EC, several molecular alterations are being explored for targeted therapy. Summary: Molecular alterations are frequently found in endometrial cancer and have currently not been implemented in the treatment guidelines for EC. Assessment of molecular alterations can distinguish patients that require less or more intensified adjuvant treatment. Trials investigating targeted therapies in EC are ongoing and have shown some promising results, however, more evidence is needed and results of randomized trials have to be awaited. [ABSTRACT FROM AUTHOR]