The predictive role of thrombocytosis in benign, borderline and malignant ovarian tumors

Ovarian cancer is a lethal gynecological malignancy. Although CA-125 is commonly measured in women with adnexal mass, it is estimated that it only has a positive predictive value (PPV) of 69% and a negative predictive value (NPV) of 88% for the detection of ovarian cancer. The aim of this study was to investigate the diagnostic significance and predictive impact of thrombocytosis in women with suspected or confirmed ovarian cancer. This was a retrospective study of women who had surgery for adnexal mass over a 48-month period between September 2014 and September 2018 at Swansea Gynecological Oncology Center in Wales, UK. A total of 294 women who underwent surgery for high-risk pelvic mass or biopsy-confirmed ovarian cancer were identified. 206 women (70%) had final histology confirming ovarian cancer, 54 women (18%) had benign tumors while 34 women (12%) had borderline tumors. 90/206 women (43.7%) with ovarian cancer had thrombocytosis prior to primary surgery or neoadjuvant chemotherapy compared to 8/54 (14.8%) for benign tumors and 4/34 (11.8%) for borderline tumors. Thrombocytosis was observed in 23.2%, 40%, 45.1%, and 65.1% of Stages I, II, III, and IV ovarian cancer, respectively. Thrombocytosis was a stronger predictor of ovarian malignancy in younger women of less than 60 years (p = .041). Overall, the positive likelihood ratio of platelet count in the detection of ovarian cancer was 2.61 while the negative likelihood ratio was 0.72, with a diagnostic odds ratio of 3.625. Thrombocytosis was strongly associated with advanced stage ovarian cancer (Stage III/IV) (p = .002). Interestingly, 4/8 (50%) women with thrombocytosis in the benign ovarian tumor group were diagnosed with ovarian fibroma/fibrothecoma, which often mimics advanced ovarian cancer at presentation. Predictive markers for borderline tumors continue to remain a challenge. We believe that there is a role for platelet count in primary care algorithm for women with suspected ovarian cancer. We suspect that platelets play a role in the metastasis of ovarian cancer

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

Background Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC).Methods Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node).Results Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions.Conclusions Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis.Clinical trial registration ClinicalTrials.gov NCT01505829

Diffusion-weighted MRI in Advanced Epithelial Ovarian Cancer: Apparent Diffusion Coefficient as a Response Marker.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10 -5 mm 2 s -1 ) was repeatable (upper and lower 95% limits of agreement of 12 × 10 -5 mm 2 s -1 [95% confidence interval {CI}: 6 × 10 -5 mm 2 s -1 to 18 × 10 -5 mm 2 s -1 ] and -15 × 10 -5 mm 2 s -1 [95% CI: -21 × 10 -5 mm 2 s -1 to -9 × 10 -5 mm 2 s -1 ]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article

Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study

Improved prognosis in women with multiple sclerosis (MS) undergoing immunosuppressive treatment with mitoxantrone (MITO) has led to an increased interest in the effect of such treatments on fertility. FErtility and Mitoxantrone In MS (FEMIMS) is a collaborative retrospective study aimed at evaluating the impact of MITO treatment on fertility in women with MS