No abstract

Using a case control approach, we performed a two-way comparison study between GP5؉/6؉-PCR and HPV SPF 10 -Line Blot 25 (SPF 10 ) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based screening and women attending a gynecological outpatient clinic. Cases (n ‫؍‬ 45) were women with histologically confirmed CIN 3 diagnosed within a median follow-up time of 2.7 (range, 0.2 to 7.9) years. Control samples were from women (n ‫؍‬ 264) who had developed CIN 1 lesions at maximum (median follow-up at 5. Based on the fact that a persistent infection with high-risk human papillomavirus (hrHPV) is the necessary cause of cervical cancer (4, 20), hrHPV testing has been recognized as a potentially valuable tool not only for the triage of women with borderline cytomorphological abnormalities but also for primary cervical screening, either in conjunction with cytology testing or not. Support for this comes from various clinical studies (1,6,9,10,16,26). It should be realized, however, that hrHPV tests might detect both transient and persistent hrHPV infections, of which only the latter represent a condition that ultimately may result in the development of grade 3 cervical intraepithelial neoplasia (CIN 3) lesions and cervical cancer (ՆCIN 3) and therefore should be considered as clinically relevant. We previously hypothesized that various hrHPV tests, although similarly efficient in detecting persistent infections, may differ considerably in the extent with which transient, clinically irrelevant hrHPV infections are detected (28).A clinically valuable hrHPV test should perform in such a way that the number of transient infections detected is as low as possible to ensure an optimal balance between clinical sensitivity and specificity for ՆCIN 3. This is important to minimize the number of unnecessary follow-up procedures, particularly for women with normal cytology results. Based on data from longitudinal clinical studies involving large cohorts, so far only the GP5ϩ/6ϩ-PCR and the commercially available hrHPV hybrid capture 2 (hc2) assays have been proven to reach such an optimal balance and therefore can be considered clinically validated (2,5,7,9,16,17,21,24). In a previous two-way comparison study, we showed that these assays, which both detect hrHPV types as a pool, perform equally well for the detection of ՆCIN 3 in a population-based cervical screening setting (13).Besides GP5ϩ/6ϩ-PCR and hc2, the consensus HPV SPF 10 -Line Blot 25 linear probe assay (SPF 10 -LiPA version 1) PCR assay (15) (referred to herein as SPF 10 ) is a commonly used HPV detection assay, particularly in epidemiological studies and vaccination trials (12). However, this method has not yet

Our findings established that a clear proportion of oophorectomized BRCA1/2 mutation carriers experience demoralization impacting on their well-being. Further research is needed to explore the natural trajectory of demoralization and the resultant need for support in these women.

Dynamic risk predictions based on all available information are useful in timely identification of high‐risk patients. However, in contrast with time to event outcomes, there is still a lack of studies that clearly demonstrate how to obtain and update predictions for a future binary outcome using a repeatedly measured biomarker. The aim of this study is to give an illustrative overview of four approaches to obtain such predictions: likelihood based two‐stage method (2SMLE), likelihood based joint model (JMMLE), Bayesian two‐stage method (2SB), and Bayesian joint model (JMB). We applied the approaches to provide weekly updated predictions of post–molar gestational trophoblastic neoplasia (GTN) based on age and repeated measurements of human chorionic gonadotropin (hCG). Discrimination and calibration measures were used to compare the accuracy of the weekly predictions. Internal validation of the models was conducted using bootstrapping. The four approaches resulted in the same predictive and discriminative performance in predicting GTN. A simulation study showed that the joint models outperform the two‐stage methods when we increase the within‐ and the between‐patients variability of the biomarker. The applicability of these models to produce dynamic predictions has been illustrated through a comprehensive explanation and accompanying syntax (R and SAS®).

5519 Background: Cytoreductive surgery and systemic therapy are essential for newly diagnosed ovarian cancer. We conducted a multicenter phase 3 trial to study whether the addition of intraperitoneal chemotherapy under hyperthermic conditions (HIPEC) to interval cytoreductive surgery would improve outcome among patients receiving neo-adjuvant chemotherapy for stage III epithelial ovarian cancer. Methods: We randomly assigned patients who showed at least stable disease after three cycles of carboplatin (area under the curve 6) and paclitaxel (175 mg/m2) to receive interval cytoreductive surgery with or without HIPEC using cisplatin (100 mg/m2). Randomization was performed per-operatively and eligible patients had no residual mass greater than 2.5 mm. Three additional cycles of carboplatin and paclitaxel were given post-operatively. The primary endpoint was recurrence-free survival. Overall survival, toxicity, and quality-of-life were key secondary endpoints. Results: A total of 245 patients were randomly assigned to one of the two treatment strategies. In an intention-to-treat analysis, interval cytoreductive surgery with HIPEC was associated with longer recurrence-free survival than interval cytoreductive surgery alone (15 vs. 11 months, respectively; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49 to 0.86; P=0.003). At the time of analysis, 49% of patients were alive, with a significant improvement in overall survival favoring HIPEC (48 vs. 34 months; HR, 0.64; 95% CI, 0.45 to 0.91, P=0.01). The number of patients with grade 3-4 adverse events was similar in both treatment arms (28% vs. 24%, p=0.61). Quality-of-life analysis will follow. Conclusions: The addition of HIPEC to interval cytoreductive surgery is well tolerated and improves recurrence free and overall survival in patients with stage III epithelial ovarian cancer. Clinical trial information: NCT00426257.