RESUMEN
BACKGROUND: Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients' survival analysis. METHODS: Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic. RESULTS: Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis. CONCLUSIONS: The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017.
Asunto(s)
Neoplasias Endometriales , Imagen por Resonancia Magnética , Modelos de Riesgos Proporcionales , Humanos , Femenino , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Anciano , Curva ROC , Adulto , Modelos Estadísticos , RadiómicaRESUMEN
Tertiary lymphoid structure (TLS) is associated with prognosis in copy-number-driven tumors, including high-grade serous ovarian cancer (HGSOC), although the function of TLS and its interaction with copy-number alterations in HGSOC are not fully understood. In the current study, we confirm that TLS-high HGSOC patients show significantly better progression-free survival (PFS). We show that the presence of TLS in HGSOC tumors is associated with B cell maturation and cytotoxic tumor-specific T cell activation and proliferation. In addition, the copy-number loss of IL15 and CXCL10 may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed. Last, a radiomics-based signature is developed to predict the presence of TLS, which independently predicts PFS in both HGSOC patients and immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients. Overall, we reveal that TLS coordinates intratumoral B cell and T cell response to HGSOC tumor, while the cancer genome evolves to counteract TLS formation and function.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Cistadenocarcinoma Seroso , Neoplasias Pulmonares , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Pulmonares/patología , Pronóstico , Tejido Linfoide , Neoplasias Ováricas/patologíaRESUMEN
PURPOSE: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. METHODS: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. RESULTS: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. CONCLUSION: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.
RESUMEN
With increased use of mass spectrometry imaging (MSI) in support of pharmaceutical research and development, there are opportunities to develop analytical pipelines that incorporate exploratory high-performance analysis with higher capacity and faster targeted MSI. Therefore, to enable faster MSI data acquisition we present analyte-targeted desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) utilizing a triple-quadrupole (TQ) mass analyzer. The evaluated platform configuration provided superior sensitivity compared to a conventional time-of-flight (TOF) mass analyzer and thus holds the potential to generate data applicable to pharmaceutical research and development. The platform was successfully operated with sampling rates up to 10 scans/s, comparing positively to the 1 scan/s commonly used on comparable DESI-TOF setups. The higher scan rate enabled investigation of the desorption/ionization processes of endogenous lipid species such as phosphatidylcholines and a co-administered cassette of four orally dosed drugs-erlotininb, moxifloxacin, olanzapine, and terfenadine. This was used to enable understanding of the impact of the desorption/ionization processes in order to optimize the operational parameters, resulting in improved compound coverage for olanzapine and the main olanzapine metabolite, hydroxy-olanzapine, in brain tissue sections compared to DESI-TOF analysis or matrix-assisted laser desorption/ionization (MALDI) platforms. The approach allowed reducing the amount of recorded information, thus reducing the size of datasets from up to 150 GB per experiment down to several hundred MB. The improved performance was demonstrated in case studies investigating the suitability of this approach for mapping drug distribution, spatially resolved profiling of drug-induced nephrotoxicity, and molecular-histological tissue classification of ovarian tumors specimens.
RESUMEN
BACKGROUND: This study aimed to assess the impact of multiple COVID-19 waves on UK gynaecological-oncology services. METHODS: An online survey was distributed to all UK-British-Gynaecological-Cancer-Society members during three COVID-19 waves from 2020 to2022. RESULTS: In total, 51 hospitals (including 32 cancer centres) responded to Survey 1, 42 hospitals (29 centres) to Survey 2, and 39 hospitals (30 centres) to Survey 3. During the first wave, urgent referrals reportedly fell by a median of 50% (IQR = 25-70%). In total, 49% hospitals reported reduced staffing, and the greatest was noted for trainee doctors, by a median of 40%. Theatre capacity was reduced by a median of 40%. A median of 30% of planned operations was postponed. Multidisciplinary meetings were completely virtual in 39% and mixed in 65% of the total. A median of 75% of outpatient consultations were remote. By the second wave, fewer hospitals reported staffing reductions, and there was a return to pre-pandemic urgent referrals and multidisciplinary workloads. Theatre capacity was reduced by a median of 10%, with 5% of operations postponed. The third wave demonstrated worsening staff reductions similar to Wave 1, primarily from sickness. Pre-pandemic levels of urgent referrals/workload continued, with little reduction in surgical capacity. CONCLUSION: COVID-19 led to a significant disruption of gynaecological-cancer care across the UK, including reduced staffing, urgent referrals, theatre capacity, and working practice changes. Whilst disruption eased and referrals/workloads returned to normal, significant staff shortages remained in 2022, highlighting persistent capacity constraints.
RESUMEN
Ovarian cancer survival in the UK lags behind comparable countries. Results from the ongoing National Ovarian Cancer Audit feasibility pilot (OCAFP) show that approximately 1 in 4 women with advanced ovarian cancer (Stage 2, 3, 4 and unstaged cancer) do not receive any anticancer treatment and only 51% in England receive international standard of care treatment, i.e., the combination of surgery and chemotherapy. The audit has also demonstrated wide variation in the percentage of women receiving anticancer treatment for advanced ovarian cancer, be it surgery or chemotherapy across the 19 geographical regions for organisation of cancer delivery (Cancer Alliances). Receipt of treatment also correlates with survival: 5 year Cancer survival varies from 28.6% to 49.6% across England. Here, we take a systems wide approach encompassing both diagnostic pathways and cancer treatment, derived from the whole cohort of women with ovarian cancer to set out recommendations and quality performance indicators (QPI). A multidisciplinary panel established by the British Gynaecological Cancer Society carefully identified QPI against criteria: metrics selected were those easily evaluable nationally using routinely available data and where there was a clear evidence base to support interventions. These QPI will be valuable to other taxpayer funded systems with national data collection mechanisms and are to our knowledge the only population level data derived standards in ovarian cancer. We also identify interventions for Best practice and Research recommendations.
RESUMEN
BACKGROUND: Determination of survival time in women with endometrial cancer using clinical features remains imprecise. Features from MRI may improve the survival estimation allowing improved treatment planning. PURPOSE: To identify clinical features and imaging signatures on T2-weighted MRI that can be used in an integrated model to estimate survival time for endometrial cancer subjects. STUDY TYPE: Retrospective. POPULATION: Four hundred thirteen patients with endometrial cancer as training (N = 330, 66.41 ± 11.42 years) and validation (N = 83, 67.60 ± 11.89 years) data and an independent set of 82 subjects as testing data (63.26 ± 12.38 years). FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T scanners with sagittal T2-weighted spin echo sequence. ASSESSMENT: Tumor regions were manually segmented on T2-weighted images. Features were extracted from segmented masks, and clinical variables including age, cancer histologic grade and risk score were included in a Cox proportional hazards (CPH) model. A group least absolute shrinkage and selection operator method was implemented to determine the model from the training and validation datasets. STATISTICAL TESTS: A likelihood-ratio test and decision curve analysis were applied to compare the models. Concordance index (CI) and area under the receiver operating characteristic curves (AUCs) were calculated to assess the model. RESULTS: Three radiomic features (two image intensity and volume features) and two clinical variables (age and cancer grade) were selected as predictors in the integrated model. The CI was 0.797 for the clinical model (includes clinical variables only) and 0.818 for the integrated model using training and validation datasets, the associated mean AUC value was 0.805 and 0.853. Using the testing dataset, the CI was 0.792 and 0.882, significantly different and the mean AUC was 0.624 and 0.727 for the clinical model and integrated model, respectively. DATA CONCLUSION: The proposed CPH model with radiomic signatures may serve as a tool to improve estimated survival time in women with endometrial cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
Asunto(s)
Neoplasias Endometriales , Humanos , Femenino , Estudios Retrospectivos , Neoplasias Endometriales/diagnóstico por imagen , Imagen por Resonancia Magnética , Área Bajo la Curva , Curva ROCRESUMEN
Introduction: Delays in the diagnosis and treatment of endometrial cancer negatively impact patient survival. The aim of this study was to establish whether rapid evaporative ionisation mass spectrometry using the iKnife can accurately distinguish between normal and malignant endometrial biopsy tissue samples in real time, enabling point-of-care (POC) diagnoses. Methods: Pipelle biopsy samples were obtained from consecutive women needing biopsies for clinical reasons. A Waters G2-XS Xevo Q-Tof mass spectrometer was used in conjunction with a modified handheld diathermy (collectively called the 'iKnife'). Each tissue sample was processed with diathermy, and the resultant surgical aerosol containing ionic lipid species was then analysed, producing spectra. Principal component analyses and linear discriminant analyses were performed to determine variance in spectral signatures. Leave-one-patient-out cross-validation was used to test the diagnostic accuracy. Results: One hundred and fifty patients provided Pipelle biopsy samples (85 normal, 59 malignant, 4 hyperplasia and 2 insufficient), yielding 453 spectra. The iKnife differentiated between normal and malignant endometrial tissues on the basis of differential phospholipid spectra. Cross-validation revealed a diagnostic accuracy of 89% with sensitivity, specificity, positive predictive value and negative predictive value of 85%, 93%, 94% and 85%, respectively. Conclusions: This study is the first to use the iKnife to identify cancer in endometrial Pipelle biopsy samples. These results are highly encouraging and suggest that the iKnife could be used in the clinic to provide a POC diagnosis.
RESUMEN
INTRODUCTION: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the UK is 5%-10%. Despite minimally invasive surgical techniques, evidence suggests a number of healthy ovarian follicles and tissues are resected intraoperatively, resulting in subsequent decline of ovarian reserve. As such, there is an increasing demand for the implementation of fertility preservation surgery (FPS). This study will evaluate the effect on ovarian reserve following two different surgical interventions for the management of benign ovarian cysts. METHODS AND ANALYSIS: We will conduct a two-armed randomised controlled trial comparing laparoscopic ovarian cystectomy, considered gold standard treatment as per the Royal College of Obstetricians and Gynaecologists (RCOG) Green Top guidelines for the management of benign ovarian cysts, with ultrasound-guided laparoscopic ovarian cystectomy (UGLOC), a novel method of FPS. The study commencement date was October 2021, with a completion date aimed for October 2024. The primary outcome will be the difference in anti-Müllerian hormone (AMH) (pmol/L) and antral follicle count (AFC) measured 3 and 6 months postoperatively from the preoperative baseline. Secondary outcomes include assessment of various surgical and histopathological findings, including duration of hospital stay (days), duration of surgery (minutes), presence of intraoperative cyst rupture (yes/no), presence of ovarian tissue within the resected specimen (yes/no) and the grade of follicles excised within the specimen (grade 0-4). We aim to randomise 94 patients over 3 years to achieve power of 80% at an alpha level of 0.05. ETHICS AND DISSEMINATION: Findings will be published in peer-reviewed journals and presented at national and international conferences and scientific meetings. The Chelsea NHS Research and Ethics Committee have awarded ethical approval of the study (21/LO/036). TRIAL REGISTRATION NUMBER: NCT05032846.
Asunto(s)
Endometriosis , Preservación de la Fertilidad , Laparoscopía , Quistes Ováricos , Reserva Ovárica , Cistectomía/métodos , Endometriosis/cirugía , Femenino , Humanos , Laparoscopía/métodos , Quistes Ováricos/diagnóstico por imagen , Quistes Ováricos/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: There is increasing recognition that prehabilitation is important as a means of preparing patients physically and psychologically for cancer treatment. However, little is understood about the role and optimal nature of prehabilitation for gynaecological cancer patients, who usually face extensive and life-changing surgery in addition to other treatments that impact significantly on physiological and psychosexual wellbeing. REVIEW QUESTION: This scoping review was conducted to collate the research evidence on multimodal prehabilitation in gynaecological cancers and the related barriers and facilitators to engagement and delivery that should be considered when designing a prehabilitation intervention for this group of women. METHODS: Seven medical databases and four grey literature repositories were searched from database inception to September 2021. All articles, reporting on multimodal prehabilitation in gynaecological cancers were included in the final review, whether qualitative, quantitative or mixed-methods. Qualitative studies on unimodal interventions were also included, as these were thought to be more likely to include information about barriers and facilitators which could also be relevant to multimodal interventions. A realist framework of context, mechanism and outcome was used to assist interpretation of findings. RESULTS: In total, 24 studies were included in the final review. The studies included the following tumour groups: ovarian only (n = 12), endometrial only (n = 1), mixed ovarian, endometrial, vulvar (n = 5) and non-specific gynaecological tumours (n = 6). There was considerable variation across studies in terms of screening for prehabilitation, delivery of prehabilitation and outcome measures. Key mechanisms and contexts influencing engagement with prehabilitation can be summarised as: (1) The role of healthcare professionals and organisations (2) Patients' perceptions of acceptability (3) Factors influencing patient motivation (4) Prehabilitation as a priority (5) Access to prehabilitation. IMPLICATIONS FOR PRACTICE: A standardised and well evidenced prehabilitation programme for women with gynaecological cancer does not yet exist. Healthcare organisations and researchers should take into account the enablers and barriers to effective engagement by healthcare professionals and by patients, when designing and evaluating prehabilitation for gynaecological cancer patients.
Asunto(s)
Neoplasias de los Genitales Femeninos , Ejercicio Preoperatorio , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Personal de Salud , Humanos , Investigación CualitativaRESUMEN
During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.
Asunto(s)
COVID-19/epidemiología , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de los Genitales Femeninos/terapia , Femenino , Ginecología , Humanos , Pandemias , SARS-CoV-2/aislamiento & purificación , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).
Asunto(s)
Antineoplásicos/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/cirugía , Anciano , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Modelos de Riesgos Proporcionales , Calidad de Vida , Análisis de SupervivenciaRESUMEN
The COVID-19 pandemic resulted in significant reconfiguration of gynecologic cancer services and care pathways across the globe, with a transformation of working practices. Services had to adapt to protect their vulnerable patients from infection, whilst providing care despite reduced resources/capacity and staffing. The international gynecologic cancer community introduced modified clinical care guidelines. Remote working, reduced hospital visiting, routine COVID-testing, and use of COVID-free surgical areas/hubs enabled the ongoing and safe delivery of complex cancer care, with priority levels for cancer treatments established to guide decision-making by multidisciplinary tumor boards. Some 2.3 million cancer surgeries were delayed or cancelled during the first peak, with many patients reporting significant anxiety/concern for cancer progression and COVID infection. Although COVID trials were prioritized, recruitment to other cancer trials/research activity was significantly reduced. The impact of resultant protocol deviations on outcomes remains to be established. During the recovery healthcare services must maintain capacity and flexibility to manage future surges of infection, address the large backlog of patients with altered or delayed treatments, along with salvaging screening and prevention services. Training needs/mental well-being of trainees need addressing and staff burnout prevented. Future research needs to fully evaluate the impact of COVID-19 on long-term patient outcomes.
Asunto(s)
COVID-19 , Neoplasias de los Genitales Femeninos , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Salud Mental , Pandemias , SARS-CoV-2RESUMEN
PURPOSE: Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI. EXPERIMENTAL DESIGN: A prospective, multicenter observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centers. FEC-PET/CT, FDG-PET/CT, and DW-MRI were compared with nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable cervical cancer stage ≥ 1B1 or endometrial cancer (grade 3 any stage with myometrial invasion or grade 1-2 stage ≥ II). RESULTS: Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT and 60 underwent FEC-PET/CT. In 118 patients, 267 nodal regions were strictly correlated at histology (nodal positivity rate, 25%). Sensitivity per patient (n = 118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT was 40%*, 53%, 53%, 63%*, and 67% for all cases (*, P = 0.016); 10%, 10%, 20%, 30%, and 25% in cervical cancer (n = 40); 65%, 75%, 70%, 80% and 88% in endometrial cancer (n = 78). FDG-PET/CT outperformed nodal size (P = 0.006) and size ratio (P = 0.04) for per-region sensitivity. False positive rates were all <10%. CONCLUSIONS: All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different from other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.
Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Cuello Uterino , Imagen de Difusión por Resonancia Magnética , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética/métodos , Estadificación de Neoplasias , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Radiofármacos , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/cirugíaRESUMEN
The use of biologics in positron emission tomography (PET) imaging is an important area of radiopharmaceutical development and new automated methods are required to facilitate their production. We report an automated radiosynthesis method to produce a radiolabelled biologic via facile inverse electron demand Diels-Alder (IEDDA) "click" chemistry on a single GE FASTLab™ cassette. We exemplified the method by producing a fluorine-18 radiolabelled interleukin-2 (IL2) radioconjugate from a trans-cyclooctene (TCO) modified IL2 precursor. The radioconjugate was produced using a fully automated radiosynthesis on a single FASTLab™ cassette in a decay-corrected radiochemical yield (RCY, d.c.) of 19.8 ± 2.6% in 110 min (from start of synthesis); the molar activity was 132.3 ± 14.6 GBq µmol-1. The in vitro uptake of [18F]TTCO-IL2 correlated with the differential receptor expression (CD25, CD122, CD132) in PC3, NK-92 and activated human PBMCs. The automated method may be adapted for the radiosynthesis of any TCO-modified protein via IEDDA chemistry.
RESUMEN
A uterine transplantation is a nonvital, quality-of-life-enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability. METHODS: A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation. RESULTS: The majority of respondents "strongly agreed" or "agreed" that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed. CONCLUSIONS: This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly.
RESUMEN
OBJECTIVE: To determine the anxiety and stress levels of women with suspected endometrial cancer and factors affecting this. METHODS: Prospective survey and paired observational study of consecutive women with suspected endometrial cancer in a rapid access gynaecology clinic. Structured questionnaire including a GAD-7 anxiety test and a modified stress thermometer were used. Patients ranked their perception of a cancer diagnosis on 0-5 Likert scale (0 = confident not cancer and 5 = cancer). Patients requiring an endometrial tissue biopsy were asked to rank their pain on a visual analogue scale (VAS), this was paired with the survey results. RESULTS: 250 patients completed the study and 23 of which underwent an endometrial tissue biopsy. The median age was 50-59 years old and 59% of women spoke English as their first language. 32% of patients had significant levels of anxiety with GAD-7 score ≥10. The median stress score was three out of five on Likert scale. GAD-7 anxiety scores were higher in women who perceived that they received insufficient information prior to clinic (sufficient information 5 vs. insufficient information 9.5, P = 0.00036) or had a disability (disability 9 vs. no disability 5.5, P = 0.00374). The median VAS score from the biopsies was seven out of 10 (range 1-10). Patients with higher anxiety levels (GAD-7 scores) were more likely to believe they had cancer P <0.00001. CONCLUSIONS: These findings confirm high levels of anxiety and stress in women with suspected endometrial cancer. Adequate pre-clinic information is essential, particularly for minority groups.
Asunto(s)
Ansiedad , Neoplasias Endometriales , Ansiedad/diagnóstico , Ansiedad/epidemiología , Neoplasias Endometriales/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
STUDY QUESTION: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer? SUMMARY ANSWER: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer. WHAT IS KNOWN ALREADY: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious. STUDY DESIGN, SIZE, DURATION: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences of breast (OR 0.86; 95% CI 0.73-1.01) and endometrial (OR 1.28; 95% CI 0.92-1.79) cancers were not found to be significantly different between the FT and no-FT groups. Whilst overall ovarian cancer incidence was not significantly different between the FT and no-FT groups (OR 1.19; 95% CI 0.98-1.46), separate analysis of borderline ovarian tumours (BOT) revealed a significant association (OR 1.69; 95% CI 1.27-2.25). In further sub-group analyses, ovarian cancer incidence was shown to be significantly higher in the IVF (OR 1.32; 95% CI 1.03-1.69) and clomiphene citrate (CC) treatment group (OR 1.40; 95% CI 1.10-1.77), respectively when compared with the no-FT group. Conversely, the incidences of breast (OR 0.75; 95% CI 0.61-0.92) and cervical cancer (OR 0.58; 95% CI 0.38-0.89) were significantly lower in the IVF treatment sub-group compared to the no-FT group. LIMITATIONS, REASONS FOR CAUTION: The large, varied dataset spanning a wide study period introduced significant clinical heterogeneity. Thus, results have to be interpreted with an element of caution. Exclusion of non-English citations, unpublished work and abstracts, in order to ensure data accuracy and reliability was maintained, may have introduced a degree of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The results for breast, ovarian, endometrial and cervical cancer are reassuring, in line with previously published meta-analyses for individual cancers but the association between IVF and CC treatment and an increase in ovarian cancer incidence requires additional work to understand the potential mechanism driving this association. In particular, focusing on (i) discriminating specific treatments effects from an inherent risk of malignancy; (ii) differential risk profiles among specific patient sub-groups (refractory treatment and obesity); and (iii) understanding the impact of FT outcomes on cancer incidence. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive any funding. The authors have no financial, personal, intellectual and professional conflicts of interest to declare. PROSPERO REGISTRATION NUMBER: CRD42019153404.
Asunto(s)
Infertilidad , Neoplasias , Femenino , Fertilidad , Fertilización In Vitro , Humanos , Infertilidad/epidemiología , Infertilidad/terapia , Neoplasias/epidemiología , Inducción de la Ovulación , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC. METHODS: ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells. RESULTS: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells. CONCLUSIONS: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/genética , Ciclina E/genética , Retrovirus Endógenos , Perfilación de la Expresión Génica/métodos , Proteínas Oncogénicas/genética , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/inmunología , Línea Celular Tumoral , Decitabina/farmacología , Decitabina/uso terapéutico , Retrovirus Endógenos/efectos de los fármacos , Femenino , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Linfocitos Intraepiteliales/efectos de los fármacos , Linfocitos Intraepiteliales/inmunología , Mutación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Pronóstico , Análisis de Secuencia de ARN , Análisis de SupervivenciaRESUMEN
The British Gynecological Cancer Society and the British Association of Gynecological Pathologists established a multidisciplinary consensus group comprising experts in surgical gynecological oncology, medical oncology, genetics, and laboratory science, and clinical nurse specialists to identify the optimal pathways to BRCA germline and tumor testing in patients with ovarian cancer in routine clinical practice. In particular, the group explored models of consent, quality standards identified at pathology laboratories, and experience and data from pioneering cancer centers. The group liaised with representatives from ovarian cancer charities to also identify patient perspectives that would be important to implementation. Recommendations from these consensus group deliberations are presented in this manuscript.