AIMS:Mortality for cervical cancer varies between the different regions of the world, with high rates in low-income countries where screening programmes are not present and organised. However, increasing screening coverage is still a priority in all countries: one way to do that is to base screening on self-sampled screening. The success of a self-sampling screening strategy depends on capacity to recruit unscreened women, on the performance and acceptability of the device and on the clinical performance of the high-risk human papillomavirus (HPV) test.METHODS:This study based on 786 enrolled women investigates the best cut-off value of Hybrid Capture 2 HPV test (HC2) for self-sampled specimens in terms of sensitivity and specificity.RESULTS:In this population, we found that the sensitivity and the specificity for cervical intraepithelial neoplasia grade 2 or more detection of HC2 performed on self-sampled specimens were 82.5% and 82.8%, respectively considering the relative light units (RLU) cut-off value of 1. Increasing the cut-off value the sensitivity decreases and the specificity raises and the best area under the curve for the RLU cut-off value is 1.CONCLUSIONS:Our results confirm that the cut-off value of 1 suggested by Qiagen for PreservCyt specimen is the best cut-off value also for self-sampled specimens.

ABSTRACT Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%.

Objective The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. Methods Three hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. Results Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. Conclusions Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.

Uterus-sparing hormonal treatment of patients affected by well-differentiated endometrial carcinoma is becoming an important issue. High doses of oral progesterone is the most common drug for treating these patients. However, the levonorgestrel intruterine device has recently been shown to be effective in some patients with a strong desire for future pregnancies or with high surgical risk. Local administration of the hormone therapy, moreover, can avoid the most frequent adverse side effects caused by oral progesterone. Patient selection to exclude preexisting myoinvasive or distant disease is a crucial, although imperfect, prerequisite. Given the risks of disease progression or relapse, close follow-up during and after treatment to monitor failures is crucial. Therefore, in this article we review the current evidence regarding the efficacy of the levonorgestrel-intrauterine device for treating well-differentiated endometrial carcinoma limited to the endometrium.

Presentations Risk Assessment in the Management of Abnormal Screening Tests: Is There a ROLE for Colposcopic Grading? S. Igidbashian*, S. Boveri*, N. Spolti*, C. Casadio*, D. Radice*, M.T. Sandri*, M Sideri. Preventive Gynaecology Unit, IEO (European Institute of Oncology), Milan, ITALY; Diagnostic Cytopathology Unit, IEO, Milan, ITALY; Division of Epidemiology and Biostatistics, IEO, Milan, ITALY; Laboratory Medicine Unit, IEO, Milan, ITALY. Objective: In the recent past data from studies investigating highly sensitive molecular tests have challenged the ability of colposcopy to detect cervical pre-cancers. Colposcopy is a technique to identify the area to place a biopsy, and so colposcopy result equals the biopsy pathology report. It has been suggested that the entire cervical cancer screening process can be viewed as a risk stratification system where the result of different exams, cytology, molecular analysis etc., acts as risk stratifier which trigger intervention (closer follow up or treatment). In this way the patient is managed by level of risk and not on the basis of the histologic diagnosis of a colposcopic directed biopsy. We tested the hypothesis that colposcopic impression alone can act as risk stratifier in patients with abnormal screen results. Methods: Data from 388 patients submitted to LEEP or laserconization were analyzed. The pathology results of the excised specimen served as gold standard. Results of Pap smear, high risk (HR) HPV test, HPV genotyping and colposcopy at the time of treatment were recorded. Pap smear results were classified according to the 2001 Bethesda system; HR HPV test results as positive or negative; HPV genotyping as high risk 16 positive or high risk HPV non 16 positive; colposcopy results as negative, grade 1, grade 2 or suspicion of invasive cancer. Results: When grade 2 colposcopy results were associated with a positive Pap smear result at an ASC-US threshold, the histology of the excised specimen was CIN2+ in 85% of the cases and when it was associated with any positive HR HPV test in 89% of the cases; conversely the finding of a grade 1 colposcopy result in the presence of an high grade intraepithelial lesion (HSIL) at cytology or in the presence of a positive HPV 16 test result predicted CIN2+ at histology in about 70% of the cases. Conclusions: The results suggest that colposcopic pattern and grading without histology can be used as risk stratifier in a management algorithm based on risk stratification.

To compare the pre-surgical ability of a multivariate predictive algorithm combining CA 125, HE4 and menopausal status (ROMA®) vs. ultrasound (US) imaging performed by an experienced examiner, for estimation of the risk of malignancy in patients with adnexal masses. Prospective multi-center, double blind, clinical trial enrolling patients presenting with adnexal masses and candidate for surgical treatment. Blood samples for HE4 and CA 125 measurements and US were performed within 30 days prior to surgery. Masses were classified by US according to IOTA criteria: the examiner classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant. A separate self impression of presumed histological diagnosis was given. Separate logistic regression algorithms for pre- and post-menopausal women were utilized to categorize patients into low and high risk group for ovarian cancer (ROMA®). Outcome measures were sensitivity (Sens), specificity (Spec), positive predictive value (PPV) and negative predictive value (NPV) of ROMA, CA 125 and HE4 and US in discriminating adnexal masses. To date 51 patients entered in the study. At final pathology there were 23 malignancies, 3 borderline tumors and 25 benign diseases. The different tests performed as follow: US (Sens 100%, Spec 89.3%, PPV 88.9%, NPV 100%), ROMA® (Sens 91.3%, Spec 89.7%, PPV 87.5%, NPV 92.9%), HE4 (Sens 91.3%, Spec 89.3%, PPV 87.5%, NPV 92.6%), CA 125 (Sens 90.7%, Spec 57.1%, PPV 64.7%, NPV 88.9%. The algorithm ROMA® has a similar accuracy in discriminating adnexal masses compared to HE4 and superior to CA 125 alone. US expertise opinion remains superior. Combination of biomarkers could offer an improvement in the preoperative triage of adnexal masses to centers of excellence.

BACKGROUND To test the efficacy of levonorgestrel-release intrauterine device (LNG-IUD) plus gonadotropin-releasing hormone (GnRH) for treating women aged <40 years with atypical endometrial hyperplasia (AEH) or presumed International Federation of Gynecology and Obstetrics stage IA limited to the endometrium, well differentiated (G1), endometrioid endometrial cancer (EC), who wish to preserve their fertility. PATIENTS AND METHODS A prospective observational study was conducted. Treatment consisted on the insertion of an LNG-IUD for 1 year plus GnRH analogue for 6 months. RESULTS From January 1996 to June 2009, 20 and 14 patients with AEH and EC, respectively, were studied. Complete response rate was 95% in patients with AEH and 57.1% in women with EC-G1. A progression of the disease was observed in one (5%) and in four patients (28%) with AEH and EC, respectively. Four of 20 patients with AEH and 2 of 14 with EC-G1 experienced recurrences. The average relapse time was 36 months (range: 16-62 months). All of them were alive without evidence of disease at the last follow-up, mean: 29 months (range: 4-102 months). Nine women achieved 11 spontaneous pregnancies. CONCLUSIONS The combined treatment showed effectiveness in a substantial proportion of patients with AEH and EC. Close follow-up during and after treatment is crucial.

The aim of the present study was to evaluate the correlation between preoperative TVUS and pathologic findings on the surgical specimen in early stage cervical cancer. From June 2007 through January 2009, 34 patients with hystological proven cervical cancer received TVUS plus Power Doppler before undergoing radical hysterectomy. TVUS accuracy was evaluated in defining tumour presence, size and parametrial involvement. Subjective assessment of tumour vascularization was recorded and correlated to vascular space involvement. According to institution's guidelines all patients underwent radical hysterectomy and pelvic lymphadenectomy. TV pre-surgical imaging results were compared to final pathological reports. Median age of the patients was 43 years (range 23–76 yrs); at final pathology according to pTNM classification 4 pts were at stage pT1A1, 20 pts pT1B1 (4 pN1), 2 pts pT1B2, one patient was pT2A pN1 and 4 pts pT2B, no residual tumor was found in 3 patients. TVUS accuracy for tumor detection was 82,4% even in ten cases of small tumour (less than 1 cm), compared to 80% of MRI. 3 pts were not correctly identified, but received prior neoadjuvant chemotherapy and 1 pts was a pT1A1. Comparing tumour maximum diameter at TVUS and final pathology the exact concordance (millimeters + 20%) was 58,8% in tumours sized more than 20 mm. Parametrial involvement was correctly detected by TVUS with an accuracy of the 95,7%. Tumor intensity of vascularization well correlated to vascular space involvement (73,7%), depth of infiltration (> 13, 5 mm) and positive lymph node (75%). These results confirm the accuracy of TVUS in presurgical evaluation of small cervical cancers and a possible aid of TVUS in identification of patients at risk who can require an adjuvant treatment. Evaluation of post-cone residual disease is very helpful in conservative treatment programs.

Borderline ovarian tumor is a tumor of epithelial origin with low malignant potential. Given its good prognosis, conservative surgical treatment can be considered in younger patients of childbearing age. However, the risk of recurrence in conservatively treated patients is well described. In this prospective study we evaluated the effectiveness of transvaginal ultrasound (TVUS) in the early detection of ovarian recurrences. From March 1997 to October 2006, 60 patients underwent fertility-sparing surgery for borderline ovarian tumors and were all followed at our institution by the same two expert sonographers. All women underwent a 4-month follow-up for the first 2 years with clinical evaluation and TVUS, and every 6 months thereafter a measurement of serum biomarkers was requested as well. Fourteen patients at different FIGO stages at onset of the disease (FIGO Stage IA–IIIC) developed a recurrence after a median of 19.8 (range, 6–51) months after primary conservative surgery. All of them were diagnosed as having at least an adnexal cyst (range, 1–4 cysts), mainly unilocular with a mean diameter of 29 (range, 10–53) mm with endoluminal papillae (mean 2.1 (range, 1–4) papillae), except in one case. Ultrasonographic detection of normal ovarian tissue allowed a further conservative surgical approach in 12 cases. Five patients had a third conservative operation and one a fourth procedure. Four patients conceived after their first fertility-sparing surgery, and two after a second and third relapse respectively. Bimanual examination was suspicious in two cases and tumor biomarkers at relapse were positive in three cases. TVUS correctly identified all tumor recurrences and allowed further fertility-sparing surgery in young patients. These data show that TVUS is the most effective diagnostic procedure during follow-up and the early detection of borderline tumor recurrence in young patients treated conservatively.

5056 Background: HistoScanning (HS) is a medical device developed to improve interpretation of echography. Ovarian (OV) HistoScanning (OVHS) performs computerized analysis of voxel files generated during transvaginal ultrasonography (TVS). OVHS was integrated into a protocol for investigation of ovarian pathologies, primarily cancer (OVCa). Methods: A study was initiated; a/ to standardize the echography procedure, b/ to evaluate OVHS ability to differentiate cancerous to non-cancerous pelvic masses under appropriate conditions. Women (W) ≥18 years old planned to have complete removal of ≥1 OV were eligible. Exclusion criteria include previous diagnosis of OV cancer, pelvic surgery, radiotherapy or chemotherapy for breast or OVCa. Real 3D-TVS were performed before surgery and the voxel data sent to AMD. After OVHS results were locked in the study’s data base, pathological reports were sent to the clinical research organization and the OVHS results were compared to histology. Results: From 09.2004 to 07.2005, 486 data files were obtained from 9 institutions. 120 were used for calibration, 97 had no surgery, and 269 met the protocol requirements. Pelvic histology includes normal OV (87), benign tumors (T) (78), past endometriosis (9), borderline cancers (21), adenocarcinomas (53), carcinomatosis (12), metastases (4) and other cancers (3), others (2). 91 cancers were correctly diagnosed (sensitivity 98%). Reason for false negatives was: lack of voxel data for the lesion (1) and pathology volume bellow US resolution (‘Cystadenofibroma with foci of low malignant potential; Borderline‘) (1). When gain used during TVS was appropriate, the false positive (FP) rate was 3% for normal tissues and 17% for benign tumors. When gain used was inappropriate, FP rate was 10% and 41%, respectively. Conclusion: OVHS seems highly sensitive for the diagnosis of pelvic masses while having an acceptable specificity. A study using 3D-TVS performed with controlled gain level is ongoing. [Table: see text]

Histoscanning (HS) is a medical device developed to improve interpretation of echography. Ovarian (OV) HistoScanning (OVHS) performs computerized analysis of voxel files generated during transvaginal ultrasonography (TVS). The targeted intended use is for the clinical assessment of pelvic masses in order to determine the type and timing, and improve the efficacy of exploratory surgeries. Thus, OVHS was designed to achieve a sensitivity of 100%. Women ≥ 18 years old scheduled to have complete removal of one or more ovaries were eligible. Exclusion criteria included previous diagnosis of cancer, pelvic surgery, radiotherapy or chemotherapy for breast or ovarian cancer. Real 3D-TVS were performed before surgery and the voxel data analyzed by OVHS. After registration of OVHS results in the study's database, pathology reports were reviewed and OVHS readings were compared to histology by an independent party. Analysis by the study's scientific steering committee of 269 data files in August 2005 reported the following: Pelvic histology: normal ovaries (87), benign tumors (78), past endometriosis (9), borderline cancers (21), adenocarcinomas (53), carcinomatosis (12), metastases (4) and other cancers (3), others (2). OVHS results: 91 cancers were correctly diagnosed by OVHS (sensitivity 98%). Reasons for false negatives were: lack of voxel data for the lesion (1) and pathology volume below US resolution (“Cystadenofibroma with foci of low malignant potential; Borderline”) (1). When electronical gain used during TVS was appropriate, the false positive (FP) rate was 3% for normal tissues and 17% for benign tumors. An identical study using 3D-TVS performed with controlled gain level is ongoing with results expected by July 2006. OVHS seems highly sensitive for the diagnosis of pelvic malignant masses while having an acceptable specificity.

OBJECTIVE:The sensitivity of the Pap smear (PAP) continues to be the subject of debate. During the past several years, cervicography (CER) and HPV DNA testing have been suggested as optional tools in the screening of cervical cancer precursors.STUDY DESIGN:The performance characteristics of PAP, CER and HPV DNA testing (hybrid capture test [HCT]) in all potential combinations were evaluated in a series of 1,030 women (aged 16-70, median, 33), subjected to colposcopy (COLPO) as the reference tool.RESULTS:Of the 992 evaluable cases, 402/992 (41%) had positive COLPO (i.e., an abnormal transformation zone). Of them, 298 women underwent directed punch biopsy, while of the COLPO negative patients, 18/93 positive by at least one of the three tests had endocervical curettage. Of the 402 COLPO positive women, 146 (36%) remained negative on all tests, whereas 256 (64%) had at least one positive test. There were 84 cervical intraepithelial neoplasia (CIN) 2 and 3 lesions and 6 invasive carcinomas. Of the former, 10 were detected by PAP alone, 4 by CER alone and 3 by HCT alone. Three of the 6 carcinomas were HCT negative. The predictive value (PPV) of a positive test was 45% for PAP, 51% for CER and 48% for HCT. The combinations of PAP with CER (for PAP negative cases) and PAP with HCT were more sensitive for CIN 2 and 3 (95% and 94%, respectively) as compared with PAP alone but were associated with a significant decrease in specificity (44% and 46% vs. 57%, respectively). However, both combinations retained a PPV (43%) similar to that of PAP alone (45%).CONCLUSION:The potential combinations of PAP with CER and with HCT were more sensitive in detecting CIN 2 and 3 as compared with PAP alone and retained a PPV similar to that of PAP.

Despite improvements seen in median and overall survival using a combination of platinum-compounds and paclitaxel (PTX), long-term survival rates for patients with advanced epithelial ovarian carcinoma remain disappointing and ongoing efforts have aimed to develop more effective primary therapy. In the early 1990Os the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior compared to the platinum-based control arm with an improvement of overall response rate, median progression-free interval and overall median survival. These favourable data were confirmed by a European-Canadian Intergroup trial (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in survival between CP alone and the combination of PTX and CP. The International Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP-based control arm. The last analysis performed with a total of 1,293 events showed an estimated absolute difference in one-year progression-free survival of 1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin. The results of ICON3, in accordance with GOG132 study, appear to contradict the earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective first-line treatments for women requiring chemotherapy for ovarian cancer. A meta-analysis with individual patient data is warranted to better clarify the issue of PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is often utilised in patients with advanced ovarian cancer, due to the high frequency of recurrent disease even after a clinical or pathological complete response after primary chemotherapy. Main objectives of salvage chemotherapy include: i. improvement in quality of life and symptoms; ii. tumour load reduction and survival advantage; iii. evaluation of potentially active new drugs to be included in first-line. Since the goal is palliation in most cases, monotherapy is generally indicated. However, the chances of response are directly related to the treatment-free interval, with a response rate nearly equivalent to that of primary chemotherapy when the treatment-free interval exceeds 24 months. Extension of the platinum-free interval before re-treatment with platinum or taxanes may allow partial reversal of resistance to these agents which can therefore still show significant activity in relapsing patients. Unfortunately, durable response to salvage chemotherapy is rare and cure is almost impossible. The sequential use of the agents currently available for salvage treatment in monotherapy may transform ovarian cancer into a chronic disease and confers long survival to the patients. Perhaps, the most interesting role of second-line chemotherapy is to identify new potentially active drugs, which can be moved up-front. Most of the compounds used in second line (gemcitabine, topotecan, liposomal doxorubicin) are in fact under investigation to develop alternative schedules and sequences of drug administration. A new phase III multi-national randomised study for patients with advanced stage epithelial ovarian or primary periperitoneal carcinoma will evaluate the impact of incorporating a new drug within either a platinum-based triplet (new drug + platinum + PTX) or a sequential-doublet (new drug + platinum followed by platinum + PTX) in order to identify one or more experimental regimens able to improve long-term survival with acceptable toxicity.

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1–T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. © 2000 Cancer Research Campaign

Screening for cervical cancer and its precursors, has traditionally been performed by Papanicolau (PAP) smear. Unfortunately, false-negative results are inevitable in cytology laboratories and the sensitivity of PAP-test continues to be subject of debate. To encompass this problem other approaches to screening have been considered. During the past several years Cervicography and HPV-DNA testing have been implicated as optional tools in the screening of cervical cancer precursors. In this study the sensitivity and specificity of PAP-test in the detection of CIN were determined in 1030 (992 valuables) consecutive women seen at our Institutions, and controlled by target biopsy in case of atypical transformation zone. Our results show that latest technology can enhance the screening techniques traditionally used and can increase the positive and negative predictive value of the screening methods.

BACKGROUND:Pathologic lymph node status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Intraoperative lymphoscintigraphy associated with gamma detecting probe-guided surgery has proved to be reliable in the detection of sentinel node (SN) involvement in melanoma and breast cancer patients. The present study evaluates the feasibility of the surgical identification of inguinal sentinel nodes using lymphoscintigraphy and a gamma detecting probe in patients with early vulvar cancer.METHODS:Technetium-99-labeled colloid human albumin was administered perilesionally in 44 patients. Twenty patients had T1 and 23 had T2 invasive epidermoid vulvar cancer; one patient had a lower-third vaginal cancer. An intraoperative gamma detecting probe was used to identify SNs during surgery. Complete inguinofemoral node dissection was subsequently performed. SNs underwent separate pathologic evaluation.RESULTS:A total of 77 groins were dissected in 44 patients. SNs were identified in all the studied groins. Thirteen cases had positive nodes: the SN was positive in all of them; in 10 cases the SN was the only positive node. Thirty-one patients showed negative SNs: all of them were negative for lymph node metastasis.CONCLUSIONS:Lymphoscintigraphy and SN biopsy under gamma detecting probe guidance proved to be an easy and reliable method for detection of SNs in early vulvar cancer. If these preliminary data will be confirmed, the technique would represent a real progress towards less aggressive treatment in patients with vulvar cancer.

Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients.A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life.The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (CI) 11.1–21.0] versus 20.1 weeks for group 2 (95% CI = 13.1–33.4); P = 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% CI 32.0–45.3) versus 45.7 weeks (95% CI 35.6–58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity.Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.NCT00382811.

The assessment of the clinical value of sonohysterography (SHG), to detect endometrial abnormalities in asymptomatic post-menopausal patients on Tamoxifen therapy is the aim of the present study. Out of 500 patients, 126 (25%), were recognized to have an endometrial thickness of more than 8 mm at transvaginal sonography (TVS). Among the 100 patients who underwent to the procedure, SHG allowed to identify 53 endometrial polyps, all confirmed at hysteroscopy and hystology and 26 suspected hyperplasias. In this latter group, 12 hyperplasias were confirmed and two endometrial cancers were found at hystology. We did not have any false negative. SHG showed to be safe, easy to perform and more accurate than TVS alone in identifying endometrial pathologies.

Cervicography and HPV DNA testing have been proposed as intermediate triage techniques for the management of patients with Pap smear showing minor-grade atypia. The aims of the present study of 221 patients with positive Pap smear (ages 16–65) were (1) to evaluate the association of cervicography and HPV DNA test with the probability of biopsy and final histology diagnosis of CIN2 or worse, (2) to identify the combinations of results on cervicography and HPV DNA test associated with the absence of such lesions, and (3) to estimate the cost of a potential triage protocol for patients with HPV-CIN1 smear. The probability of biopsy showed a univariate association with the severity of the smear result and the cervicography classification but not the HPV DNA test. In the multivariate analysis, only the cervicography result was a significant predictor of biopsy. The final histology diagnosis showed a univariate association with each of the three tests and a multivariate association with the degree of cytology positivity and the cervicography result. Among patients with HPV-CIN1 smears, only a negative cervicography (with any HPV DNA test result) was always associated with the absence of severe histologic lesions. This pattern accounted only for 7% of such patients. The additional costs of a potential triage protocol based on cervicography were estimated to exceed the savings resulting from the reduced colposcopy rate.