David Oram

Minia University, Minya, Al Minyā, Egypt

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Publications (67)456.76 Total impact

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    ABSTRACT: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 05/2015; 33(18). DOI:10.1200/JCO.2014.59.4945 · 18.43 Impact Factor
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    ABSTRACT: Background: Cervical cancer is the second commonest cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. Sources suggest that a very high proportion of new cervical cancer cases in developing countries are at an advanced stage (IB2 or more) and more than a half of these may be stage III or IV. Cervical cancer staging is based on findings from clinical examination (FIGO) staging). Standard care in Europe and US for stage IB2 to III is non-surgical treatment (chemoradiation). However in developing countries, where there is limited access to radiotherapy, locally advanced cervical cancer may be treated with a combination of chemotherapy and hysterectomy (surgery to remove the womb and the neck of the womb, with or without the surrounding tissues). It is not certain if this improves survival. Therefore, it is important to systematically assess the value of hysterectomy in addition to radiotherapy or chemotherapy, or both, as an alternative intervention in the treatment of locally advanced cervical cancer (stage IB2 to III). Objectives: To determine whether hysterectomy, in addition to standard treatment with radiation or chemotherapy, or both, in women with locally advanced cervical cancer (stage IB2 to III) is safe and effective compared with standard treatment alone. Search methods: We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, MEDLINE, EMBASE and LILACS up to February 2014. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria: We searched for randomised controlled trials (RCTs) that compared treatment protocols involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with advanced stage (IB2 to III) cervical cancer presenting for the first time. Data collection and analysis: We assessed study eligibility independently, extracted data and assessed risk of bias. Where possible, overall and progression or disease-free survival outcomes were synthesised in a meta-analysis using the random-effects model. Adverse events were incompletely reported so results of single trials were described in narrative form. Main results: We included seven RCTs (1217 women) of varying methodological quality in the review; most trials were at moderate or high risk of bias.Three were multi-centre trials, two were single-centre trials, and in two trials it was unclear if they were single or multi-centre. These trials compared the following interventions for women with locally advanced cervical cancer (stages IB2 to III):hysterectomy (simple or radical) with radiotherapy (N = 194) versus radiotherapy alone (N = 180); hysterectomy (simple or radical) with chemoradiotherapy (N = 31) versus chemoradiotherapy alone (N = 30); hysterectomy (radical) with chemoradiotherapy (N = 111) versus internal radiotherapy with chemoradiotherapy (N = 100); hysterectomy (simple or radical) with upfront (neoadjuvant) chemotherapy (N = 298) versus radiotherapy alone (N = 273).One trial (N = 256) found no difference in the risk of death or disease progression between women who received attenuated radiotherapy followed by hysterectomy and those who received radiotherapy (external and internal) alone (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.61 to 1.29). This trial also reported no difference between the two groups in terms of adverse effects (18/129 grade 3 or 4 adverse effects in the hysterectomy and radiation group and 19 cases in 18/121 women in the radiotherapy alone group). There was no difference in 5-year tumour-free actuarial survival (representation of the probable years of survivorship of a defined population of participants) or severe complications (grade 3) in another trial (N = 118) which reported the same comparison (6/62 versus 6/56 in the radiation with surgery group versus the radiotherapy alone group, respectively). The quality of the evidence was low for all these outcomes.One trial (N = 61) reported no difference (P value > 0.10) in overall and recurrence-free survival at 3 years between chemoradiotherapy and hysterectomy versus chemoradiotherapy alone (low quality evidence). Adverse events and morbidity data were not reported.Similarly, another trial (N = 211) found no difference in the risk of death (HR 0.65, 95% CI 0.35 to 1.21, P value = 0.19, low quality evidence), disease progression (HR 0.70, 95% CI 0.31 to 1.34, P value = 0.24, low quality evidence) or severe late complications (P value = 0.53, low quality evidence) between women who received internal radiotherapy versus hysterectomy after both groups had received external-beam chemoradiotherapy.Meta analysis of three trials of neoadjuvant chemotherapy and hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received neoadjuvant chemotherapy plus hysterectomy had less risk of death than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93, I(2) = 0%, moderate quality evidence). However, a significant number of the participants that received neoadjuvant chemotherapy plus hysterectomy had radiotherapy as well. There was no difference in the proportion of women with disease progression or recurrence between the two groups (RR 0.75, 95% CI 0.53 to 1.05, I(2) = 20%, moderate quality evidence).Results of single trials reported no apparent (P value > 0.05) difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between the two groups (low quality evidence).Quality of life outcomes were not reported in any of the trials. Authors' conclusions: From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with locally advanced cervical cancer who are treated with radiotherapy or chemoradiotherapy alone. The overall quality of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The quality of the evidence for neoadjuvant chemotherapy and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate, with evidence from other comparisons of low quality. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials that assess medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.
    Cochrane database of systematic reviews (Online) 04/2015; 4:CD010260. DOI:10.1002/14651858.CD010260.pub2 · 6.03 Impact Factor
  • Fani Kokka · Andy Bryant · David Oram · Melanie Powell
    Cochrane database of systematic reviews (Online) 01/2013; DOI:10.1002/14651858.CD010260 · 6.03 Impact Factor
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    ABSTRACT: To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I and aggressive Type II EOC in postmenopausal women with adnexal abnormalities on ultrasound. This was a prospective cohort study in the ultrasound group of the UK Collaborative Trial of Ovarian Cancer Screening of postmenopausal women with ultrasound-detected abnormal adnexal (unilocular, multilocular, unilocular solid and multilocular solid, solid) morphology on their first scan. Women were followed up through the national cancer registries and by postal questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC within 3 years of initial scan were calculated. Of 48 053 women who underwent ultrasound examination and had complete scan data, 4367 (9.1% (95% CI, 8.8-9.3%)) had abnormal adnexal morphology. Median follow-up was 7.09 (25(th) -75(th) centiles, 6.03-7.92) years. Forty-seven (32 borderline or Type I, 15 Type II) were diagnosed with EOC. The overall absolute risk of EOC associated with abnormal adnexal morphology was 1.08% (95% CI, 0.79-1.43%); for borderline and Type I it was 0.73% (95% CI, 0.5-1.03%); and for Type II it was 0.34% (95% CI, 0.33-0.79%). In the subgroup (n = 741) with solid elements (unilocular solid, multilocular solid and solid) overall absolute risk was 4.45% (95% CI, 3.08-6.20%), for borderline and Type I it was 3.1% (95% CI, 1.9-4.6%) and for Type II it was 1.3% (95% CI, 0.6-2.4%). 11 982 women had both ovaries visualized and normal annual scans throughout the 3-year follow-up period. In this group, no borderline or Type I and eight Type II cancers were diagnosed. Asymptomatic postmenopausal women with ultrasound-detected adnexal abnormalities with solid elements have a 1 in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of borderline or Type I cancer in women with ultrasound abnormalities seems to be higher than does the risk of Type II cancer. This has important immediate implications for patients with incidental adnexal findings as well as for any future ultrasound-based screening.
    Ultrasound in Obstetrics and Gynecology 09/2012; 40(3):338-44. DOI:10.1002/uog.12270 · 3.85 Impact Factor
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    ABSTRACT: To describe the outcome of primary chemotherapy for women with advanced-stage epithelial ovarian or primary peritoneal cancer and delayed surgery when optimal debulking surgery cannot be achieved at diagnosis. Between 1998 and 2006, we retrospectively reviewed the overall survival and examined prognostic markers in consecutive patients who were not suitable for initial radical surgery because of the extent of disease and/or poor performance status. They were treated with a policy of primary platinum-based chemotherapy, followed whenever possible in responding patients by debulking surgery. A total of 171 patients received least one cycle of chemotherapy. Eighty-six patients proceeded to surgery and 53 (31% of 171 and 62% of 86) had optimal (<1 cm) residual disease. Eighty-five patients did not undergo surgery because they remained unfit or had not responded sufficiently to chemotherapy. The median overall survival was 18.7 months (95% confidence interval [CI], 16.5-24.2). The median OS in the surgical group for optimal and suboptimal surgery was 40.8 (95% CI, 32.5-50.0) and 22.5 (95% CI, 17.7-37.1) months (P = 0.005). On multivariate analysis, interval surgery and optimal surgery were the only independent prognostic factors (hazard ratios, 0.45 and 0.43, respectively; P = 0.009). In the nonsurgical group, CA125 response was an independent prognostic factor (hazard ratio, 0.34; P = 0.001) with an OS of 21.7 months (95% CI, 14.0-35.4) in women with a normal CA125 after treatment compared with 6.7 (95% CI, 4.5-7.8) months. In one third of the women, the tumor was optimally debulked after primary chemotherapy and their median survival was 40.8 months. Suboptimal debulking surgery after primary chemotherapy did not result in a better survival than that achieved after a chemotherapy response alone, suggesting that surgery may be avoided when imaging after chemotherapy demonstrates residual disease that cannot be optimally debulked.
    International Journal of Gynecological Cancer 03/2012; 22(4):566-72. DOI:10.1097/IGC.0b013e318247727f · 1.95 Impact Factor
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    ABSTRACT: To evaluate factors affecting uptake of risk-reducing salpingo-oophorectomy (RRSO) over time in women at high-risk of familial ovarian cancer. Prospective observational cohort. Tertiary high-risk familial gynaecological cancer clinic. New clinic attendees between March 2004 and November 2009, fulfilling the high-risk criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed included RRSO and ovarian surveillance. Outcome data were analysed from a bespoke database. The competing risk method was used to model the cumulative incidence function (CIF) of RRSO over time, and the sub-hazard ratio (SHR) was used to assess the strength of the association of variables of interest with RRSO. Gray's test was used to evaluate the difference in CIF between two groups and multivariable competing risk regression analysis was used to model the cumulative probabilities of covariates on the CIF. Of 1133 eligible women, 265 (21.4%) opted for RRSO and 868 (69.9%) chose screening. Women undergoing RRSO were older (49 years, interquartile range 12.2 years) than those preferring screening (43.4 years, interquartile range 11.9 years) (P < 0.0005). The CIF for RRSO at 5 years was 0.55 (95% CI 0.45-0.64) for BRCA1/2 carriers and 0.22 (95% CI 0.19-0.26) for women of unknown mutation status (P < 0.0001); 0.42 (95% CI 0.36-0.47) for postmenopausal women (P < 0.0001); 0.29 (95% CI 0.25-0.33) for parity ≥1 (P = 0.009) and 0.47 (95% CI 0.39-0.55) for a personal history of breast cancer (P < 0.0001). Variables of significance from the regression analysis were: a BRCA1/2 mutation (SHR 2.31, 95% CI 1.7-3.14), postmenopausal status (SHR 2.16, 95% CI 1.62-2.87)) and a personal history of breast cancer (SHR 1.5, 95% CI 1.09-2.06). Decision-making is a complex process and women opt for surgery many years after initial risk assessment. BRCA carriers, postmenopausal women and women who had breast cancer are significantly more likely to opt for preventative surgery.
    BJOG An International Journal of Obstetrics & Gynaecology 01/2012; 119(5):527-36. DOI:10.1111/j.1471-0528.2011.03257.x · 3.45 Impact Factor
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    ABSTRACT: To compare surgical outcomes and occult cancer rates at risk-reducing salpingo-oophorectomy in BRCA carriers and high-risk women who had not undergone genetic testing. Prospective cohort study. Tertiary high-risk familial gynaecological cancer clinic. Women undergoing risk-reducing salpingo-oophorectomy between January 2005 and November 2009. Women at high-risk of ovarian/tubal cancer were identified on the basis of the inclusion criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed with 1456 high-risk women included risk-reducing salpingo-oophorectomy. A strict histopathological protocol with serial slicing was used to assess tubes and ovaries. In total, 308 high-risk women (191 with unknown mutation status; 117 known BRCA1/BRCA2 carriers) chose risk-reducing surgery; 94.5% of procedures were performed laparoscopically. The surgical complication rate was 3.9% (95% CI 2.0-6.7). Four ovarian and ten tubal occult invasive/in situ cancers were found. The overall occult invasive cancer rate was 5.1% (95% CI 1.9-10.83) in BRCA1/BRCA2 carriers and 1.05% (95% CI 0.13-3.73) in untested women. When tubal in situ cancers were included, the overall rate was 4.55% (95% CI 2.5-7.5). Two untested women with tubal carcinoma in situ were subsequently found to be BRCA carriers. The median ages of BRCA carriers (58 years; IQR 13.4 years) and untested women (49.5 years; IQR 20.6 years) with occult invasive/in situ cancer were not significantly different (P = 0.454). Both high-risk women of unknown mutation status and BRCA carriers have a significant (although higher in the latter group) rate of occult invasive/in situ tubal/ovarian cancer, with a similar age distribution at detection. The data has important implications for counselling high-risk women on the likelihood of occult malignancy and perioperative complications at risk-reducing salpingo-oophorectomy. Women with occult disease should be offered genetic testing.
    BJOG An International Journal of Obstetrics & Gynaecology 03/2011; 118(7):814-24. DOI:10.1111/j.1471-0528.2011.02920.x · 3.45 Impact Factor
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    ABSTRACT: Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status. Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs) were calculated based on national mortality (2005) and cancer incidence (2006) statistics. The Index of Multiple Deprivation (IMD 2007) was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations. The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived) than the national average, those who joined the trial were less deprived. Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent to use the various mortality and incidence rates presented as guides for calculating event rates and power in RCTs involving women.
    Trials 03/2011; 12(1):61. DOI:10.1186/1745-6215-12-61 · 1.73 Impact Factor
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    ABSTRACT: The increase in the worldwide incidence of endometrial cancer relates to rising obesity, falling fertility, and the ageing of the population. Transvaginal ultrasound (TVS) is a possible screening test, but there have been no large-scale studies. We report the performance of TVS screening in a large cohort. We did a nested case-control study of postmenopausal women who underwent TVS in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) following recruitment between April 17, 2001, and Sept 29, 2005. Endometrial thickness and endometrial abnormalities were recorded, and follow-up, through national registries and a postal questionnaire, documented the diagnosis of endometrial cancer. Our primary outcome measure was endometrial cancer and atypical endometrial hyperplasia (AEH). Performance characteristics of endometrial thickness and abnormalities for detection of endometrial cancer within 1 year of TVS were calculated. Epidemiological variables were used to develop a logistic regression model and assess a screening strategy for women at higher risk. Our study is registered with ClinicalTrials.gov, number NCT00058032, and with the International Standard Randomised Controlled Trial register, number ISRCTN22488978. 48,230 women underwent TVS in the UKCTOCS prevalence screen. 9078 women were ineligible because they had undergone a hysterectomy and 2271 because their endometrial thickness had not been recorded; however, 157 of these women had an endometrial abnormality on TVS and were included in the analysis. Median follow-up was 5·11 years (IQR 4·05-5·95). 136 women with endometrial cancer or AEH within 1 year of TVS were included in our primary analysis. The optimum endometrial thickness cutoff for endometrial cancer or AEH was 5·15 mm, with sensitivity of 80·5% (95% CI 72·7-86·8) and specificity of 86·2% (85·8-86·6). Sensitivity and specificity at a 5 mm or greater cutoff were 80·5% (72·7-86·8) and 85·7% (85·4-86·2); for women with a 5 mm or greater cutoff plus endometrial abnormalities, the sensitivity and specificity were 85·3% (78·2-90·8) and 80·4% (80·0-80·8), respectively. For a cutoff of 10 mm or greater, sensitivity and specificity were 54·1% (45·3-62·8) and 97·2% (97·0-97·4). When our analysis was restricted to the 96 women with endometrial cancer or AEH who reported no symptoms of postmenopausal bleeding at the UKCTOCS scan before diagnosis and had an endometrial thickness measurement available, a cutoff of 5 mm achieved a sensitivity of 77·1% (67·8-84·3) and specificity of 85·8% (85·7-85·9). The logistic regression model identified 25% of the population as at high risk and 39·5% of endometrial cancer or AEH cases were identified within this high risk group. In this high-risk population, a cutoff at 6·75 mm achieved sensitivity of 84·3% (71·4-93·0) and specificity of 89·9% (89·3-90·5). Our findings show that TVS screening for endometrial cancer has good sensitivity in postmenopausal women. The burden of diagnostic procedures and false-positive results can be reduced by limiting screening to a higher-risk group. The role of population screening for endometrial cancer remains uncertain, but our findings are of immediate value in the management of increased endometrial thickness in postmenopausal women undergoing pelvic scans for reasons other than vaginal bleeding.
    The Lancet Oncology 01/2011; 12(1):38-48. DOI:10.1016/S1470-2045(10)70268-0 · 24.69 Impact Factor
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    ABSTRACT: Endometrial cancer is cancer arising from the lining of the womb. Most women with endometrial cancer are diagnosed when their tumour is still confined to the body of the womb. However, about 10% of women with endometrial cancer are diagnosed when the disease is already at an advanced stage. The latter group of patients tend to have much poorer survival. Treatment of women with advanced or recurrent endometrial cancer is challenging because often they suffer from other diseases and aggressive chemotherapy with or without surgery may not be beneficial or may even be harmful. Hormonal therapy in these cases is thought to be easily administered and to cause fewer side effects than systemic chemotherapy (standard treatment). The purpose of this review was to assess the available literature on the effect of hormonal treatment on the survival of patients with advanced or recurrent endometrial cancer. We found six randomised controlled trials (RCTs) that assessed hormonal treatment in various forms and combinations in 542 eligible patients. We found insufficient evidence to suggest that hormonal therapy improves survival in these patients. The main limitations of the review were the small number of patients included in the RCTs, the diversity of both the patient population and the hormonal agents used and the fact that quality of life was not reported in any of the trials. The quality of life with treatment is especially important for a condition that has a poor survival rate.
    Cochrane database of systematic reviews (Online) 12/2010; 12(12):CD007926. DOI:10.1002/14651858.CD007926.pub2 · 6.03 Impact Factor
  • Fani Kokka · Jeyarajah A · Oram D
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    J Warwick · D Oram · A Covens · S Duffy · K Reynolds
    BJOG An International Journal of Obstetrics & Gynaecology 12/2009; 117(1):114 - 116. DOI:10.1111/j.1471-0528.2009.02429.x · 3.45 Impact Factor
  • Histopathology 12/2009; 55(6):756-8. DOI:10.1111/j.1365-2559.2009.03435.x · 3.45 Impact Factor
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    ABSTRACT: Diagnosis of ovarian cancer at early stages increases the likelihood for effective treatment and long-term survival. Preliminary data from a randomized controlled trial suggested a survival benefit of routine screening for ovarian cancer sequentially with the CA-125 blood test and ultrasound (multimodal screening). This randomized controlled trial — the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) — assessed the effect of screening with CA-125 and transvaginal ultrasound on mortality. Between 2001 and 2005, a total of 202,638 postmenopausal women aged 50 to 74 years were randomly assigned to 3 groups: (1) a no treatment control group receiving no ovarian screening (n = 101,359); (2) an annual CA-125 screening group with transvaginal ultrasound scan as a second-line test (multimodal screening [MMS] [n = 50,640]); or (3) an annual screening transvaginal ultrasound group (USS) (n = 50, 639). The serum CA-125 tumor marker was measured from blood samples. For the prevalence screen, 50,078 (98·9%) women underwent MMS, and 48,230 (95·2%) were screened with USS. Overall, 4555 (9.1%) of the MMS women and 5779 (12.0%) of the USS women had unsatisfactory or abnormal scans and required a repeat test. A total of 167 (0.3%) of the MMS women and 1894 (3.9%) of the USS women who underwent the initial prevalence screening required clinical evaluation; 97 (0.2%) of the MMS women and 845 (1.8%) of the USS women had surgery to remove both ovaries and fallopian tubes for examination. Primary ovarian or tubal malignancies were detected in 42 women in the MMS group and 45 in the USS group; of these, 8 MMS and 20 USS were borderline tumors. Overall, 48.3% (28/58) of the total invasive cancers detected were early stages I/II (12 MMS and 16 USS). There was no significant difference (P = 0.396) in stage distribution between the groups. Within 1 year of a normal prevalence screen test, 13 additional (interval) ovarian and tubal cancers were diagnosed; 5 were MMS, and 8 USS. The sensitivity and specificity values for MMS to detect primary invasive ovarian and tubal cancers were 89.5% and 99.8% whereas these same values for USS were 75.0%, and 98.2%, respectively. Compared with the USS, these values were significantly higher with the MMS for specificity (P < 0.0001) but not for sensitivity. The investigators conclude from these findings that routine screening of women at normal risk is feasible and may improve detection rates of early ovarian cancer. Whether mortality rates are reduced by screening cannot be determined until the study is completed in 2014.
    Obstetrical and Gynecological Survey 09/2009; 64(9):592-593. DOI:10.1097/01.ogx.0000358020.23155.ac · 1.86 Impact Factor
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    ABSTRACT: To establish the optimal management strategy for women with suspected stage 1 ovarian cancer. We created a flowchart to illustrate each of six hypothetical management strategies. These considered two surgical approaches (systematic lymphadenectomy versus no lymph node dissection at all) in combination with three different policies for giving adjuvant chemotherapy. Gynaecological cancer centre, London, UK. Patient data and published papers. We developed a deterministic model that uses information from multiple sources to estimate patient flow through each level of a hypothesised decision tree. We estimated that for every 100 cases of suspected early-stage ovarian cancer, there would be 37 cases with 'apparent' stage 1 disease and that of these, two (6%) would be denied potentially life-saving adjuvant treatment if systematic lymphadenectomy was not performed. The number of women given chemotherapy would not, according to our estimates, differ greatly between the two surgical approaches, the 7% increase with systematic lymphadenectomy being because of cases identified as having nodal metastases. We present a model of the intraoperative decision-making process that determines the extent of the staging procedure to be performed within our department when early-stage ovarian cancer is suspected. Unless adjuvant chemotherapy is prescribed for all, systematic pelvic and para-aortic node dissection is required to optimise survival. However, in our department, this would result in 32% of women with suspected early-stage ovarian cancer undergoing systematic node dissection. This flexible focused model may facilitate multidisciplinary team discussion when this part of the surgical staging procedure is considered within the context of the population presenting to the team, the morbidity of the procedure within the department and the predictive values of frozen section within that department. As the model is not disease-specific, it may be useful for decision making in other medical disciplines.
    BJOG An International Journal of Obstetrics & Gynaecology 06/2009; 116(9):1225-41. DOI:10.1111/j.1471-0528.2009.02213.x · 3.45 Impact Factor
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    ABSTRACT: Ovarian cancer has a high case-fatality ratio, with most women not diagnosed until the disease is in its advanced stages. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomised controlled trial designed to assess the effect of screening on mortality. This report summarises the outcome of the prevalence (initial) screen in UKCTOCS. Between 2001 and 2005, a total of 202 638 post-menopausal women aged 50-74 years were randomly assigned to no treatment (control; n=101 359); annual CA125 screening (interpreted using a risk of ovarian cancer algorithm) with transvaginal ultrasound scan as a second-line test (multimodal screening [MMS]; n=50 640); or annual screening with transvaginal ultrasound (USS; n=50 639) alone in a 2:1:1 ratio using a computer-generated random number algorithm. All women provided a blood sample at recruitment. Women randomised to the MMS group had their blood tested for CA125 and those randomised to the USS group were sent an appointment to attend for a transvaginal scan. Women with abnormal screens had repeat tests. Women with persistent abnormality on repeat screens underwent clinical evaluation and, where appropriate, surgery. This trial is registered as ISRCTN22488978 and with ClinicalTrials.gov, number NCT00058032. In the prevalence screen, 50 078 (98.9%) women underwent MMS, and 48 230 (95.2%) underwent USS. The main reasons for withdrawal were death (two MMS, 28 USS), non-ovarian cancer or other disease (none MMS, 66 USS), removal of ovaries (five MMS, 29 USS), relocation (none MMS, 39 USS), failure to attend three appointments for the screen (72 MMS, 757 USS), and participant changing their mind (483 MMS, 1490 USS). Overall, 4355 of 50 078 (8.7%) women in the MMS group and 5779 of 48 230 (12.0%) women in the USS group required a repeat test, and 167 (0.3%) women in the MMS group and 1894 (3.9%) women in the USS group required clinical evaluation. 97 of 50 078 (0.2%) women from the MMS group and 845 of 48 230 (1.8%) from the USS group underwent surgery. 42 (MMS) and 45 (USS) primary ovarian and tubal cancers were detected, including 28 borderline tumours (eight MMS, 20 USS). 28 (16 MMS, 12 USS) of 58 (48.3%; 95% CI 35.0-61.8) of the invasive cancers were stage I/II, with no difference (p=0.396) in stage distribution between the groups. A further 13 (five MMS, eight USS) women developed primary ovarian cancer during the year after the screen. The sensitivity, specificity, and positive-predictive values for all primary ovarian and tubal cancers were 89.4%, 99.8%, and 43.3% for MMS, and 84.9%, 98.2%, and 5.3% for USS, respectively. For primary invasive epithelial ovarian and tubal cancers, the sensitivity, specificity, and positive-predictive values were 89.5%, 99.8%, and 35.1% for MMS, and 75.0%, 98.2%, and 2.8% for USS, respectively. There was a significant difference in specificity (p<0.0001) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers. The sensitivity of the MMS and USS screening strategies is encouraging. Specificity was higher in the MMS than in the USS group, resulting in lower rates of repeat testing and surgery. This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group. The prevalence screen has established that the screening strategies are feasible. The results of ongoing screening are awaited so that the effect of screening on mortality can be determined.
    The Lancet Oncology 04/2009; 10(4):327-40. DOI:10.1016/S1470-2045(09)70026-9 · 24.69 Impact Factor
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    ABSTRACT: To determine the accuracy of naked eye assessment of surgical margins after formalin fixation in vulval cancer in comparison with microscopic assessment. Retrospective review. The Gynaecological Cancer Centre, St Bartholomew's Hospital, London, U.K. Patients with primary vulval cancer who underwent surgery from 1997 to 2006. Histopathology reports were reviewed and data on surgical margins were analysed. After formalin fixation, pathologists analysed surgical margins and measured them with a ruler. This measurement was compared with microscopic measurement. Other clinicopathologic variables were also recorded and compared. Comparison between macroscopic and microscopic measurement, and the relation to clinicopathological variables. Naked eye assessment of surgical margins was within 2 mm of correlated microscopic measurement in 29 patients (Group 1). In ten patients the macroscopic measurement of clear margins was less than the microscopic (Group 2). In the remaining 11 cases (22%) naked eye observation overestimated the normal skin margins (Group 3). Seven patients from this group eventually fell into the unfavourable prognostic category of surgical margins <8 mm. The presence of LVSI was significantly more frequent in Group 3 than in the other two groups (p = 0.01). The difference between other variables of the study groups was statistically non-significant. Our study demonstrates that naked eye assessment of surgical margins after formalin fixation is inaccurate and that surgical margins are often inadequate. We conclude that tumours with LVSI should be considered for a wider surgical excision.
    European journal of gynaecological oncology 02/2008; 29(5):455-8. · 0.61 Impact Factor
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    ABSTRACT: To describe the factors that contributed to successful recruitment of more than 200,000 women to the UK Collaborative Trial of Ovarian Cancer Screening, one of the largest ever randomised controlled trials. Descriptive study. 13 NHS trusts in England, Wales, and Northern Ireland. Postmenopausal women aged 50-74; exclusion criteria included ovarian malignancy, bilateral oophorectomy, increased risk of familial ovarian cancer, active non-ovarian malignancy, and participation in other ovarian cancer screening trials. Achievement of target recruitment, acceptance rates of invitation, and recruitment rates. The trial was set up in 13 centres with 27 adjoining local health authorities. The coordinating centre team was led by one of the senior investigators, who was closely involved in planning and day to day trial management. Of 1 243,282 women invited, 23.2% (288 955) replied that they were eligible and would like to participate. Of those sent appointments, 73.6% (205 090) attended for recruitment. The acceptance rate varied from 19% to 33% between trial centres. Measures to ensure target recruitment included named coordinating centre staff supporting and monitoring each centre, prompt identification and resolution of logistic problems, varying the volume of invitations by centre, using local non-attendance rates to determine the size of recruitment clinics, and organising large ad hoc clinics supported by coordinating centre staff. The trial randomised 202,638 women in 4.3 years. Planning and trial management are as important as trial design and require equal attention from senior investigators. Successful recruitment needs constant monitoring by a committed proactive management team that is willing to explore individual solutions for different centres and use central resources to improve local recruitment. Automation of trial processes with web based trial management systems is crucial in large multicentre randomised controlled trials. Recruitment can be further enhanced by using information videos and group discussions. Trial registration Current Controlled Trials ISRCTN22488978.
    BMJ (online) 02/2008; 337(7681):a2079. DOI:10.1136/bmj.a2079 · 17.45 Impact Factor
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    ABSTRACT: As the overall prognosis for patients with ovarian cancer is poor, the management of this condition should be restricted to expert multi-disciplinary teams in gynaecological oncology. Apparent early stage ovarian cancer requires accurate and complete staging so that potential sites for metastases are not missed. Omitting adequate staging may have significant consequences including a negative impact on survival rates in young patients. The challenge with advanced ovarian cancer is to obtain a detailed appreciation of the extent of disease. This information allows treatment with primary chemotherapy if the cancer is considered to be inoperable and/or the general condition of the patient renders her unfit for appropriate surgery. Available data would suggest that a 5-year survival rate of 50% is only possible for those patients who have had complete cytoreduction of all tumour. Therefore, the best surgical option for patients with advanced ovarian cancer is a 'complete' primary surgical procedure that achieves complete clearance of the abdominal cavity rather than 'optimal' surgery that leaves tumour nodules up to 1 cm in diameter in situ in the patient.
    Cancer Imaging 02/2007; 7(1):210-5. DOI:10.1102/1470-7330.2007.0030 · 2.07 Impact Factor
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    ABSTRACT: To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. Postmenopausal women, > or = 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.
    Journal of Clinical Oncology 12/2005; 23(31):7919-26. DOI:10.1200/JCO.2005.01.6642 · 18.43 Impact Factor

Publication Stats

3k Citations
456.76 Total Impact Points


  • 2012
    • Minia University
      • Department of Obstetrics and Gynecology
      Minya, Al Minyā, Egypt
  • 2009
    • Barts Health NHS Trust
      Londinium, England, United Kingdom
  • 2007
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2003
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1999–2001
    • Queen Mary, University of London
      • Oral Pathology
      Londinium, England, United Kingdom
  • 2000
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom
  • 1998
    • Statens Serum Institut
      København, Capital Region, Denmark
  • 1992–1993
    • University of Cambridge
      • Department of Obstetrics & Gynaecology
      Cambridge, England, United Kingdom