Cervical cancer survivors’ and partners’ experiences with sexual dysfunction and psychosexual support

Cervix cancerGynecolog

Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancer

BACKGROUND: Cervical carcinoma develops as a result of multiple genetic alterations. Different studies investigated genomic alterations in cervical cancer mainly by means of metaphase comparative genomic hybridization (mCGH) and microsatellite marker analysis for the detection of loss of heterozygosity (LOH). Currently, high throughput methods such as array comparative genomic hybridization (array CGH), single nucleotide polymorphism array (SNP array) and gene expression arrays are available to study genome-wide alterations. Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression. RESULTS: Genome-wide copy number and genotype analysis of 10 cervical cancer cell lines by array CGH and SNP array showed highly complex large-scale alterations. A comparison between array CGH and SNP array revealed that the overall concordance in detection of the same areas with copy number alterations (CNA) was above 90%. The use of SNP arrays demonstrated that about 75% of LOH events would not have been found by methods which screen for copy number changes, such as array CGH, since these were LOH events without CNA. Regions frequently targeted by CNA, as determined by array CGH, such as amplification of 5p and 20q, and loss of 8p were confirmed by fluorescent in situ hybridization (FISH). Genome-wide, we did not find a correlation between copy-number and gene expression. At chromosome arm 5p however, 22% of the genes were significantly upregulated in cell lines with amplifications as compared to cell lines without amplifications, as measured by gene expression arrays. For 3 genes, SKP2, ANKH and TRIO, expression differences were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSION: This study showed that copy number data retrieved from either array CGH or SNP array are comparable and that the integration of genome-wide LOH, copy number and gene expression is useful for the identification of gene specific targets that could be relevant for the development and progression in cervical cancer

Association between energy balance-related factors and clinical outcomes in patients with ovarian cancer: A systematic review and meta-analysis

Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥ 3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95 % CI: 1.06 – 2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95 % CI: 1.04 – 1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95 % CI: 1.62 – 2.79, p \u3c 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058

Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study

Contains fulltext : 108486.pdf (publisher's version ) (Open Access)BACKGROUND: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS). In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer. METHODS: Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS. Despite the absence of strong evidence and despite the possible complications, laparoscopy is already implemented in many countries. We propose a randomized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients. TRIAL REGISTRATION: Netherlands Trial Register number NTR2644

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality

Ménage à trois

Met de aanstelling van een hoogleraar gynaecologische oncologie als hoofd van het Centrum Gynaecologische Oncologie Amsterdam is er een samenwerkingsverband tussen de afdelingen van het AMC, NKI-AVL en VUmc ontstaan. Door deze samenwerking zullen patiënten, medewerkers en onderzoekers naar verwachting voordelen ervaren in de vorm van betere kwaliteit en hogere efficiency. In deze oratie worden enkele voorbeelden genoemd van de voordelen voor de patiëntenzorg, evenals de keuzes die worden gemaakt in het wetenschappelijk onderzoek. Verschillende scenario's worden besproken waarin de samenwerking gestalte kan krijgen

Indoleamine 2,3-dioxygenase expression pattern in the tumor microenvironment predicts clinical outcome in early stage cervical cancer

The indoleamine 2,3-dioxygenase (IDO) enzyme can act as an immunoregulator by inhibiting T cell function via the degradation of the essential amino acid tryptophan (trp) into kynurenine (kyn) and its derivates. The kyn/trp ratio in serum is a prognostic factor for cervical cancer patients; however, information about the relationship between serum levels and IDO expression in the tumor is lacking. IDO expression was studied in 71 primary and 14 paired metastatic cervical cancer samples by various immunohistochemical (IHC) techniques, including 7-color fluorescent multiparameter IHC, and the link between the concentration of IDO metabolites in serum, clinicopathological characteristics, and the presence of (proliferating) T cells (CD8, Ki67, and FoxP3) was examined. In addition, we compared the relationships between IDO1 and IFNG gene expression and clinical parameters using RNAseq data from 144 cervical tumor samples published by The Cancer Genome Atlas (TCGA). Here, we demonstrate that patchy tumor IDO expression is associated with an increased systemic kyn/trp ratio in cervical cancer (P = 0.009), whereas marginal tumor expression at the interface with the stroma is linked to improved disease-free (DFS) (P = 0.017) and disease-specific survival (P = 0.043). The latter may be related to T cell infiltration and localized IFNγ release inducing IDO expression. Indeed, TCGA analysis of 144 cervical tumor samples revealed a strong and positive correlation between IDO1 and IFNG mRNA expression levels (P < 0.001) and a significant association with improved DFS for high IDO1 and IFNG transcript levels (P = 0.031). Unexpectedly, IDO+ tumors had higher CD8+Ki67+ T cell rates (P = 0.004). Our data thus indicate that the serum kyn/trp ratio and IDO expression in primary tumor samples are not clear-cut biomarkers for prognosis and stratification of patients with early stage cervical cancer for clinical trials implementing IDO inhibitors. Rather, a marginal IDO expression pattern in the tumor dominantly predicts favorable outcome, which might be related to IFNγ release in the cervical tumor microenvironment