Development of a framework and the content for a psychoeducational internet-delivered intervention for women after treatment for gynaecological cancer

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).The number of women treated for gynecological cancer is increasing. At the same time, the duration of in-patient hospitalization has decreased, and follow-up with its primary focus on early recognition of recurrence does not meet all patients’ needs. One method of follow-up may be digital intervention. This study describes the development of a psychoeducational Internetdelivered intervention targeting women’s psychosocial needs during the follow-up period after treatment for gynecological cancer. The project consisted of three phases following the UK Medical Research Council Framework guidelines for the development of complex interventions. Phase one identified the evidence in the field, phase two identified the relevant theoretical framework, and phase three included a two-year work process including focus group interviews and think aloud interviews with users. Through the steps of literature review, theoretical framework, and an iterative development process with users and other stakeholders, a six-week program was developed. The program included psychoeducational information, multimedia, exercises, and weekly telephone follow-up with a dedicated nurse. This Internet-delivered intervention can be a novel method for addressing the gap in the provision of follow-up for women after treatment for gynecological cancer.publishedVersio

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review

Endometrial cancer is the most common gynaecological malignancy in developed countries. Over 382,000 new cases were diagnosed worldwide in 2018, and its incidence and mortality are constantly rising due to longer life expectancy and life style factors including obesity. Two major improvements are needed in the management of patients with endometrial cancer, i.e., the development of non/minimally invasive tools for diagnostics and prognostics, which are currently missing. Diagnostic tools are needed to manage the increasing number of women at risk of developing the disease. Prognostic tools are necessary to stratify patients according to their risk of recurrence pre-preoperatively, to advise and plan the most appropriate treatment and avoid over/under-treatment. Biomarkers derived from proteomics and metabolomics, especially when derived from non/minimally-invasively collected body fluids, can serve to develop such prognostic and diagnostic tools, and the purpose of the present review is to explore the current research in this topic. We first provide a brief description of the technologies, the computational pipelines for data analyses and then we provide a systematic review of all published studies using proteomics and/or metabolomics for diagnostic and prognostic biomarker discovery in endometrial cancer. Finally, conclusions and recommendations for future studies are also given

Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial

Background: Preoperative histologic examination of tumour tissue is essential when deciding if endometrial cancer surgery should include lymph node sampling. We wanted to investigate if biomarkers could improve prediction of lymph node metastasis and outcome. Patients and methods: Curettage specimens from 832 endometrial carcinoma patients prospectively recruited from 10 centres in the MoMaTEC trial (Molecular Markers in Treatment of Endometrial Cancer) were investigated for hormone receptor and p53 status. Results: Eighteen per cent of tumours were double negative for oestrogen- and progesterone receptors (ER/PR loss), 24% overexpressed p53. Pathologic expression of all markers correlated with nodal metastases, high FIGO (Federation International of Gynecology and Obstetrics) stage, non-endometrioid histology, high grade and poor prognosis (all P < 0.001). ER/PR loss independently predicted lymph node metastasis (odds ratios (OR) 2.0, 95% confidence interval (CI) 1.1–3.7) adjusted for preoperative curettage histology and predicted poor disease-specific survival adjusted for age, FIGO stage, histologic type, grade and myometrial infiltration (hazard ratio (HR) 2.3, 95% CI 1.4–3.9). For lymph node negative endometrioid tumours, ER/PR loss influenced survival independent of grade. Conclusion: Double negative hormone receptor status in endometrial cancer curettage independently predicts lymph node metastasis and poor prognosis in a prospective multicentre setting. Implementing hormone receptor status to improve risk-stratification for selecting patients unlikely to benefit from lymphadenectomy seems justified.publishedVersio

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Clinical and molecular markers in endometrial cancer. Studying prognostic and predictive biomarkers that can help to individualise therapeutic decisions

Background: Endometrial carcinoma is one of the most common cancer types in women, and incidence is increasing globally. Although many cancers are detected at an early stage and will be treated adequately with surgery alone, 15-20% of cancers will recur. After systemic recurrence, median survival approximates 7-12 months, in spite of treatment, with no improvement over the last decades. Our abilities to predict which patients will suffer recurrence, give ample room for improvement and robust prognostic biomarkers are needed to better recognise these high-risk patients. Response rates to medical treatment, both conventional and targeted, do not pass 40%, and are often considerably lower, even more so in the recurrent setting. Contrasting some other frequent cancer types such as breast and colorectal, in endometrial cancer algorithms, predictive biomarkers to support treatment choices are non-existent. Using preclinical models and large prospectively collected population-based patient series, potential biomarkers can be studied and tested at a pre-trial stage, which can accelerate the process of their identification and development, and increase the chance of succesfull trials. Objectives: We studied clinical and molecular variables for their abilities to function as prognostic or predictive biomarkers, with the ultimate aim to improve and individualise treatment strategies for endometrial cancer patients. Exploring the behaviour of these biomarkers during cancer progression, followed as a logical consequence. Materials and Methods: For all studies included in this thesis (studies 1-5) clinical data, including follow-up data, have been retrieved and analysed, either from the Haukeland University Hospital Series or from the significantly larger MoMaTEC series. The hyperplasia cohort has been studied in paper 4 and (paired) primary tumours and metastases in studies 4+5. From the biobank material, FFPE tissue has been used for immunohistochemistry (ARID1A; study 4, stathmin1; study 5), snap-frozen tissue for RNA microarrays (study 4) and haematoxylin stained frozen sections (study 3). For studies 1 and 2 only clinical data was used. Cell-line studies, including dose response studies, viral transfection techniques and immunoblotting formed a strong basis under study 5. Results: After restaging all 1268 included patients, we demonstrated an improvement and simplification of the prognostic stratification using the FIGO 2009 version. In stage 1 patients, the myometrial infiltration depth was an independent prognostic factor, only for those patients that did not undergo lymphadenectomy. Cox multivariate survival analysis showed FIGO 2009 to be a stronger, independent prognostic factor than FIGO 1988. (study 1) The 16% (207) tumours with discordant risk between preoperative and operative specimens, proved to be an interesting group with intermediate prognosis and risk of lymph node metastasis, in the entire dataset (n=1374) and in stage 1 tumours only (n=954). Cox multivariate survival analysis showed the risk classification to have independent prognostic value, and different hazard rates for the concordant high risk (HR 5.1) and discordant groups (HR 2.7 and 2.9). (study 2) High tumour cell content (n=136, 50%) was in our series associated with more aggressive disease and reduced disease specific survival. (study 3) Loss of ARID1A was linked to the endometrioid and clear cell subtypes, and associated with less aggressive disease, with the exception of the positive association with deep myometrial infiltration. No relation was found between loss of ARID1A and survival. Loss was noticed in a considerable percentage of the hyperplasias with atypia; this percentage further increased with disease progression. (study 4) Stathmin1 knockdown in cell lines was associated with increased apoptosis after paclitaxel treatment. Patients with high stathmin1 level showed worse response to paclitaxel containing chemotherapy, but not to other treatments, compared to patients with normal stathmin level using RECIST criteria. In Cox multivariate analysis, stathmin1 was an independent predictor of survival only in the subgroup of patients who received paclitaxel containing chemotherapy. (study 5) Conclusions: The FIGO 2009 classification system both simplified and improved prognostic stratification abilities compared to the previous system from 1988. (study 1) Through integration of the preoperative histology with the final or operative histology, prognostic information can be further improved, especially when discordance between both results exists and results in the identification of subgroups with intermediate risk for metastatic spread and disease specific death that currently go unnoticed. (study 2) The 80% tumour-cell content cutoff, meant to ensure high tumour purity, is, in endometrial cancer, associated with high-risk clinicopathological characteristics and reduced disease specific survival and may thus introduce an unintended selection bias. (study 3) Loss of ARID1A occurs most in endometrioid and clear cell subtypes and is predominantly linked to clinicopathological parameters of less aggressive disease, but lacks correlation with survival. Loss starts early in endometrioid endometrial cancer carcinogenesis and further increases with tumour progression. (study 4) Stathmin1 has potential as a predictive biomarker for response to paclitaxel containing chemotherapeutic regimes in endometrial cancer. (study 5) Biomarker switch is a frequent phenomenon during endometrial cancrinoma disease progression and re-assessment of biomarker status in metastatic disease may be relevant. (study 4 and 5

What is the role of imaging at primary diagnostic work-up in uterine cervical cancer?

Purpose of Review For uterine cervical cancer, the recently revised International Federation of Gynecology and Obstetrics (FIGO) staging system (2018) incorporates imaging and pathology assessments in its staging. In this review we summarize the reported staging performances of conventional and novel imaging methods and provide an overview of promising novel imaging methods relevant for cervical cancer patient care. Recent Findings Diagnostic imaging during the primary diagnostic work-up is recommended to better assess tumor extent and metastatic disease and is now reflected in the 2018 FIGO stages 3C1 and 3C2 (positive pelvic and/or paraaortic lymph nodes). For pretreatment local staging, imaging by transvaginal or transrectal ultrasound (TVS, TRS) and/or magnetic resonance imaging (MRI) is instrumental to define pelvic tumor extent, including a more accurate assessment of tumor size, stromal invasion depth, and parametrial invasion. In locally advanced cervical cancer, positron emission tomography-computed tomography (PET-CT) or computed tomography (CT) is recommended, since the identification of metastatic lymph nodes and distant metastases has therapeutic consequences. Furthermore, novel imaging techniques offer visualization of microstructural and functional tumor characteristics, reportedly linked to clinical phenotype, thus with a potential for further improving risk stratification and individualization of treatment. Summary Diagnostic imaging by MRI/TVS/TRS and PET-CT/CT is instrumental for pretreatment staging in uterine cervical cancer and guides optimal treatment strategy. Novel imaging techniques may also provide functional biomarkers with potential relevance for developing more targeted treatment strategies in cervical cancer

Redefining sexual health after gynaecological cancer:Lived experiences from Gynea, a digital rehabilitation programme

BACKGROUND: Gynaecological cancer illness and treatment have a significant impact on women's sexual health and concerns regarding sexual health are known to be an unmet need in survivors. The digital support programme Gynea was designed to enhance women's health, including sexual health, after gynaecological cancer treatment. This study aimed to explore how cancer survivors experienced participation in Gynea. METHODOLOGY: This is a phenomenological hermeneutic study. Individual, in-depth semi-structured interviews were conducted to explore lived experiences. Twenty women were interviewed after completing the Gynea programme. The transcripts were analysed using Lindseth and Norberg's phenomenological hermeneutic method. FINDINGS: Three main themes (with subthemes) emerged from the analysis: (1) A silent existential trauma; (2) Redefining sexual health; (3) Communicating with a partner about sexuality. The women redefined sexual health rather than just being sexual intercourse, being a rediscovery of the body. The women's increased awareness and understanding of their own sexual health empowered their communication about their sexuality with their partners. This was important for regaining sexual health and intimacy in their relationships. CONCLUSION: Participation in Gynea helped to strengthen the women's sexual integrity. Knowledge and support empowered them to take care of their sexual needs and communicate these with their partners. IMPLICATIONS FOR PATIENT CARE: Healthcare services and nurses need to be aware that sexual health is an existential state of being, in which good sexual health does not necessarily equate to sexual function, but rather to sexual empowerment. Digital support with nurse guidance can support women in caring for their sexual health after cancer illness by thematizing sexual health with a holistic approach and should be part of the medical treatment. PATIENT OR PUBLIC CONTRIBUTION: Twenty gynaecological cancer survivors contributed by sharing their experiences from the sexual health module in Gynea

Development of a Framework and the Content for a Psychoeducational Internet-Delivered Intervention for Women after Treatment for Gynecological Cancer

The number of women treated for gynecological cancer is increasing. At the same time, the duration of in-patient hospitalization has decreased, and follow-up with its primary focus on early recognition of recurrence does not meet all patients’ needs. One method of follow-up may be digital intervention. This study describes the development of a psychoeducational Internet-delivered intervention targeting women’s psychosocial needs during the follow-up period after treatment for gynecological cancer. The project consisted of three phases following the UK Medical Research Council Framework guidelines for the development of complex interventions. Phase one identified the evidence in the field, phase two identified the relevant theoretical framework, and phase three included a two-year work process including focus group interviews and think aloud interviews with users. Through the steps of literature review, theoretical framework, and an iterative development process with users and other stakeholders, a six-week program was developed. The program included psychoeducational information, multimedia, exercises, and weekly telephone follow-up with a dedicated nurse. This Internet-delivered intervention can be a novel method for addressing the gap in the provision of follow-up for women after treatment for gynecological cancer