Jane Bridges

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

OBJECTIVE--To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN--The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING--General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS--22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES--Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS--41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS--This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer.

MULTIMODAL APPROACH TO SCREENING FOR OVARIAN CANCER

1010 postmenopausal women were recruited for an ovarian cancer screening programme incorporating serum CA-125 measurement and vaginal examination as initial tests and real-time ultrasonography as a secondary procedure in selected cases. The normal range for serum CA-125 in postmenopausal women was established. The specificity for ovarian cancer of serum CA-125 measurement and vaginal examination were 97.0% and 97.3%, respectively. The combinations of serum CA-125 measurement with ultrasound and vaginal examination with ultrasound achieved specificities of 99.8% and 99.0%, respectively. 100% specificity was achieved by serum CA-125 measurement with vaginal examination and by the combination of all three tests. The findings indicate that no individual screening test has acceptable specificity for ovarian cancer in postmenopausal women. However, the combination of CA-125 measurement with ultrasound did achieve acceptable specificity and offers the most hope of a specific and sensitive method for early detection.

Evaluation of magnetic resonance diffusion and spectroscopy measurements as predictive biomarkers in stage 1 cervical cancer

OBJECTIVE To establish whether ADC and total choline were significantly different between cervical tumors with different histological characteristics (type, degree of differentiation, presence or absence of lymphovascular invasion, lymph-node involvement) in order to establish their role as predictive biomarkers. METHODS 62 patients with stage 1 cervical cancer were scanned at 1.5 T. T2-weighted imaging (TR/TE=4500/80 ms), to identify tumor and normal cervix, was followed by diffusion-weighted imaging (TR/TE=2500/69 ms; 5 b-values 0, 100, 300, 500 and 800 s/mm(2)) and MR spectroscopic imaging (15 mm slice, 7.5 mm in-plane resolution, TR=888 ms). Regions of interest in normal cervix and tumor were drawn on apparent diffusion coefficient (ADC) maps by an expert observer with reference to the T2-weighted images. ADCs were calculated using a monoexponential fit of data from all b-values. MR spectra in voxels designated as tumor (>30% tumor) or non-tumor were quantified using LCModel and referenced to tissue water. RESULTS There was a statistically significant difference between the ADC of tumor regions (1117+/-183x10(-6) mm(2)/s) and of selected normal regions (1724+/-198x10(-6) mm(2)/s; p<0.001), and between tumors that were well/moderately differentiated (1196+/-181x10(-6) mm(2)/s) compared with those that were poorly differentiated (1038+/-153x10(-6) mm(2)/s; p=0.016). There was no significant difference between the ADCs of the tumors when separated by other characteristics (tumor type, lymphovascular invasion, lymph-node metastases), or between measured total choline in any of the groups. CONCLUSION ADCs are lower in cancer compared to normal cervical tissue, with degree of tumor differentiation contributing to this difference.

Epithelial Ovarian Cancer Metastasizing to the Brain: A Late Manifestation of the Disease With an Increasing Incidence

PURPOSE We present the Royal Marsden Hospital experience of cerebral metastases from primary epithelial ovarian carcinoma (EOC) over the last 20 years and examine the evidence for an increasing incidence of EOC metastasizing to this site. PATIENTS AND METHODS A total of 3,690 women with EOC were seen at the Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed cerebral metastases. RESULTS Median age at diagnosis of EOC was 52 years (range, 39 to 67). All patients received at least one line of platinum-based chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four lines. The median treatment interval between each line of chemotherapy was 12, 18, and 4 months. The median interval between diagnosis and CNS relapse was 46 months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to 1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the literature also suggests that the incidence of cerebral metastases from EOC has increased over time. CONCLUSION CNS metastases in EOC are a rare and late manifestation of the disease, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses. An analysis of our data and the data from the literature suggests that the incidence of metastasis at this site in patients with EOC is increasing.

The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant women

Summary. Investigation of serum and tissue homogenates obtained from first, second and third trimester pregnancies, and from nonpregnant women, has provided further insight into the possible origin of the CA 125 antigen. Serum CA 125 levels were higher in the first trimester (median 53.6 U/ml, range 15.6.268.3 U/ml) than in nonpregnant women (median 19.3 U/ml, range 7.2.27.0 U/ml) and later in pregnancy (second trimester: median 18.5 U/ml, range 12.0.25.1 U/ml, third trimester: median 19.2 U/ml, range 16.8.43.8 U/ml) (P<0.05) but were two orders of magnitude less than in second trimester amniotic fluid (median 4825 U/ml, range 3200.9300 U/ml). Fetal serum CA 125 activity was consistently <20 U/ml. The highest tissue levels of CA 125 were detected in first trimester decidual homogenate (median 4547 U/ 100 mg, range 340.4–20 851 U/100 mg) and were greater than in nonpregnant endometrium (median 388 U/100 mg, range 100.9–3341 U/100 mg) (P<0.01) and term decidua (median 116 U/100 mg, range 32.7–449.9 U/100 mg) (P<0.01). These observations suggest that CA 125 is synthesized by normal endometrium and decidua and that increased CA 125 activity during pregnancy is of decidual origin.

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests.

BackgroundWe assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer.Methods545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing.ResultsThe median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%.ConclusionNo early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.

9 Para-aortic lymphadenectomy

Summary Para-aortic lymphadenectomy is a procedure that has an undoubted place within the management spectrum of gynaecological malignancies. It should be performed in selected cases by trained gynaecological oncologists who are versed in the technique and in the management of potential complications. The removal and histological examination of nodal tissue remains the most accurate method of assessing the precise extent of disease spread. Its main value, therefore, is as part of a surgical staging procedure, which provides reliable survival information. However, it is still questionable whether treatment planning based on this knowledge, including modification of adjuvant therapy, results in improved survival figures. Until more data are available to clarify the degree of patient benefit, para-aortic lymphadenectomy is a technique that is more suitably practised in investigative oncological centres rather than on a widespread clinical basis.