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Usha Menon - One of the best experts on this subject based on the ideXlab platform.

  • Ovarian Cancer Screening: Current status and future directions
    Best practice & research. Clinical obstetrics & gynaecology, 2020
    Co-Authors: Zachary Nash, Usha Menon
    Abstract:

    Ovarian Cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through Screening. Multimodal Ovarian Cancer Screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, Screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel Screening modalities and longitudinal biomarker algorithms offer potential improvements to future Screening strategies as does the development of better risk stratification tools.

  • Abstract KP01: UNITED KINGDOM COLLABORATIVE TRIAL OF Ovarian Cancer Screening – (UKCTOCS) – EXPLORING THE RESULTS
    Detection and Prevention of Ovarian Cancer, 2017
    Co-Authors: Usha Menon
    Abstract:

    The continued high case fatality ratio in Ovarian Cancer has underpinned efforts to develop a Screening strategy that could impact on mortality. In the general population randomised control trial - United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) two Screening strategies (multimodal MMS and ultrasound USS) were compared to no Screening (control C). Of 202,638 women randomised between April 2001-October 2005, 50,624 MMS; 50,623 USS; and 101,299 C were eligible for analysis. By the end of Screening (December 2011) 345,570 MMS and 327,775 USS annual screens were performed. At censorship for the initial mortality analysis on 31st December 2014, there was an overall significant stage shift in invasive epithelial Ovarian/tubal/peritoneal Cancer in the MMS group compared to C in an ‘intention to screen’ analysis. More detailed analysis has shown this stage shift seen in the MMS group was limited to Type II (high grade serous) Ovarian Cancers. This was associated with a delayed but not yet statistically significant mortality reduction. Disease specific mortality rates in the C arm were continuing to rise while they appeared to have plateaued in the screen arms. Further follow-up is now underway to confirm the mortality reduction and determine its full extent. Meanwhile a focus on detecting low volume disease using Cancer specific markers, novel biospecimens such as endocervical samples, targeted imaging and time series algorithms for interpreting marker profile suggest that a new era in Ovarian Cancer Screening is underway. Citation Format: Usha Menon. UNITED KINGDOM COLLABORATIVE TRIAL OF Ovarian Cancer Screening – (UKCTOCS) – EXPLORING THE RESULTS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr KP01.

  • the effect of Ovarian Cancer Screening on sexual activity and functioning results from the uk collaborative trial of Ovarian Cancer Screening rct
    British Journal of Cancer, 2017
    Co-Authors: Lesley Fallowfield, Ian Jacobs, Usha Menon, Ivonne Solistrapala, C Langridge, Valerie Jenkins
    Abstract:

    Background: To examine the impact of multimodal (MMS) and ultrasound (USS) Screening on the sexual activity and functioning of 22,966 women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) RCT. Methods: Fallowfield’s Sexual Activity Questionnaire (FSAQ) was completed prior to randomisation, then annually in a random sample (RS) of women from MMS, USS and control groups. Any women in the study who required repeat Screening due to unsatisfactory results formed an Events Sample (ES); they completed questionnaires following an event and annually thereafter. Results: Over time in the RS (n=1,339) there was no difference between the MMS and USS groups in sexual activity compared with controls. In the ES there were significant differences between the USS group (n=10,156) and the MMS group (n=12,810). The USS group had lower pleasure scores (mean difference = -0.14, P=0.046). For both groups women who had ≥2 repeat screens, showed a decrease in mean pleasure scores compared to their annual scores (mean difference = -0.16, P=0.005). Similarly mean pleasure scores decreased following more intensive screens compared to annual Screening (mean difference= -0.09, P=0.046). Conclusion: Ovarian Cancer Screening did not affect sexual activity and functioning unless a woman had abnormal results and underwent repeated or higher level Screening.

  • Abstract IA23: Ovarian Cancer Screening.
    Keynote Sessions, 2016
    Co-Authors: Usha Menon
    Abstract:

    Ovarian Cancer is the 5th most common cause of Cancer death among women in the UK, with ten-year survival rates of 35%. The continued high case fatality ratio has underpinned efforts to develop a Screening strategy that could impact on mortality. In the UK large Ovarian Cancer Screening trials have been completed both in the general (United Kingdom Collaborative Trial of Ovarian Cancer Screening - UKCTOCS) and high-risk (UK Familial Ovarian Cancer Screening Study UKFOCSS) population. Emerging evidence from UKCTOCS is encouraging with the multimodal strategy appearing to have detected double the number of invasive epithelial Ovarian/fallopian tube Cancer during incidence Screening compared to a fixed cut-off for serum CA125 used previously. The key issue is impact on Ovarian Cancer mortality, which will be available from UKCTOCS in December 2015. Meanwhile new insights into carcinogenesis with a better understanding of the target lesion, improved design of biomarker discovery studies, a focus on detecting low volume disease using Cancer specific markers, novel biospecimens such as endocervical samples, targeted imaging and time series algorithms for interpreting marker profile suggests that a new era in Ovarian Cancer Screening is underway. Citation Format: Usha Menon. Ovarian Cancer Screening. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA23.

  • Abstract CT104: Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial
    Lancet (London England), 2015
    Co-Authors: Ian Jacobs, Usha Menon, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Alistair Mcguire, Mahesh K. B. Parmar, Steven J. Skates
    Abstract:

    Background: Ovarian Cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of Ovarian Cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in Screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of Screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of Screening. One intervention arm of this trial was designed to establish the effect of early detection by Screening with blood tests on Ovarian Cancer mortality. We estimated its impact on cases arising after Screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal Screening (MMS) with serum CA125 interpreted with use of the risk of Ovarian Cancer algorithm, annual transvaginal ultrasound Screening (USS), or no Screening, in a 1:1:2 ratio. The primary outcome was death due to Ovarian Cancer by Dec 31, 2014, comparing MMS with no Screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have Ovarian Cancer, or had exited the registry before recruitment. For this report, we focused on the impact of Screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no Screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual Screening episodes. At a median follow-up of 11.1 years, we diagnosed Ovarian Cancer in 968 women: 338 in the MMS group, and 630 in the no Screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no Screening group had died of Ovarian Cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from Ovarian Cancer of MMS versus no Screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to Ovarian Cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of Screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS Screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of Ovarian Cancer Screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.

Ian Jacobs - One of the best experts on this subject based on the ideXlab platform.

  • the effect of Ovarian Cancer Screening on sexual activity and functioning results from the uk collaborative trial of Ovarian Cancer Screening rct
    British Journal of Cancer, 2017
    Co-Authors: Lesley Fallowfield, Ian Jacobs, Usha Menon, Ivonne Solistrapala, C Langridge, Valerie Jenkins
    Abstract:

    Background: To examine the impact of multimodal (MMS) and ultrasound (USS) Screening on the sexual activity and functioning of 22,966 women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) RCT. Methods: Fallowfield’s Sexual Activity Questionnaire (FSAQ) was completed prior to randomisation, then annually in a random sample (RS) of women from MMS, USS and control groups. Any women in the study who required repeat Screening due to unsatisfactory results formed an Events Sample (ES); they completed questionnaires following an event and annually thereafter. Results: Over time in the RS (n=1,339) there was no difference between the MMS and USS groups in sexual activity compared with controls. In the ES there were significant differences between the USS group (n=10,156) and the MMS group (n=12,810). The USS group had lower pleasure scores (mean difference = -0.14, P=0.046). For both groups women who had ≥2 repeat screens, showed a decrease in mean pleasure scores compared to their annual scores (mean difference = -0.16, P=0.005). Similarly mean pleasure scores decreased following more intensive screens compared to annual Screening (mean difference= -0.09, P=0.046). Conclusion: Ovarian Cancer Screening did not affect sexual activity and functioning unless a woman had abnormal results and underwent repeated or higher level Screening.

  • Abstract CT104: Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial
    Lancet (London England), 2015
    Co-Authors: Ian Jacobs, Usha Menon, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Alistair Mcguire, Mahesh K. B. Parmar, Steven J. Skates
    Abstract:

    Background: Ovarian Cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of Ovarian Cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in Screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of Screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of Screening. One intervention arm of this trial was designed to establish the effect of early detection by Screening with blood tests on Ovarian Cancer mortality. We estimated its impact on cases arising after Screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal Screening (MMS) with serum CA125 interpreted with use of the risk of Ovarian Cancer algorithm, annual transvaginal ultrasound Screening (USS), or no Screening, in a 1:1:2 ratio. The primary outcome was death due to Ovarian Cancer by Dec 31, 2014, comparing MMS with no Screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have Ovarian Cancer, or had exited the registry before recruitment. For this report, we focused on the impact of Screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no Screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual Screening episodes. At a median follow-up of 11.1 years, we diagnosed Ovarian Cancer in 968 women: 338 in the MMS group, and 630 in the no Screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no Screening group had died of Ovarian Cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from Ovarian Cancer of MMS versus no Screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to Ovarian Cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of Screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS Screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of Ovarian Cancer Screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.

  • Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
    BMC public health, 2015
    Co-Authors: Katharine Bailey, Ian Jacobs, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, M Parmar, Hynek Pikhart
    Abstract:

    Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality.

  • Psychosocial Factors Associated With Withdrawal From the United Kingdom Collaborative Trial of Ovarian Cancer Screening After 1 Episode of Repeat Screening
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2015
    Co-Authors: Valerie Jenkins, Ian Jacobs, Usha Menon, Lesley Fallowfield, C Langridge, Andy Ryan, Jessica K. Barrett, Justine Kilkerr, Vernon T. Farewell
    Abstract:

    Objective: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) aims to establish the efficacy of 2 different Ovarian Cancer Screening schedules. The psychosocial substudy examines the psychological factors associated with the Screening program. Methods: Women aged 50 to 75 years from 16 UK gynecologic centers randomized to annual multimodal Screening or ultrasound Screening (US) groups were followed up for 7 years. Psychosocial data from women who withdrew from the study after a repeat screen were examined. Results: Sixteen percent (3499/21,733) of women requiring a repeat Screening test in addition to annual screen withdrew from the study: 12.9% (1560/12,073) from the multimodal group and 20.1% (1939/9660) from the US group. An estimated relative risk of withdrawal is 1.46 (95% confidence interval, 1.36-1.56; P

  • Psychological morbidity associated with Ovarian Cancer Screening: results from more than 23,000 women in the randomised trial of Ovarian Cancer Screening (UKCTOCS).
    BJOG : an international journal of obstetrics and gynaecology, 2014
    Co-Authors: Jane Barrett, Ian Jacobs, Usha Menon, C Langridge, Andy Ryan, Jenkins, Farewell, J Kilkerr, Lesley Fallowfield
    Abstract:

    Objective To examine the psychological sequelae associated with abnormal Screening in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Design Prospective, longitudinal randomised control trial. Setting Sixteen UKCTOCS centres. Sample Women aged 50–70 years randomised to annual multimodal Screening, ultrasound Screening or control groups. Methods Two groups were followed for 7 years: (1) a random sample (n = 1339), taken from all three study groups; and (2) an events sample (n = 22 035) of women with abnormal screens resulting in the need for repeat testing of either low or higher level intensity. Main outcome measures Patient-reported measures of anxiety (scores ranging from 20 to 80) and psychological morbidity. Results In the random sample the mean difference between anxiety scores after a repeat Screening and those following an annual Screening was 0.4 (95% CI −0.46, 1.27), and in the events sample it was 0.37 (95% CI 0.23, 0.51). The risk of psychological morbidity was only increased in the event sample for women requiring higher level repeat Screening (OR 1.28; 95% CI 1.18, 1.39). The risk of psychological morbidity in women with Ovarian Cancer was higher at both 6 weeks (OR 16.2; 95% CI 9.19, 28.54) and 6 months (OR 3.32; 95% CI 1.91, 5.77) following surgery. Conclusions Screening does not appear to raise anxiety but psychological morbidity is elevated by more intense repeat testing following abnormal annual screens, and in women after surgical treatment for Ovarian Cancer.

Aleksandra Gentry-maharaj - One of the best experts on this subject based on the ideXlab platform.

  • Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women.
    Cancers, 2020
    Co-Authors: Aleksandra Gentry-maharaj, Jatinderpal Kalsi, Oleg Blyuss, Andy Ryan, Matthew Burnell, Chloe Karpinskyj, Richard Gunu, Anne Dawnay, Inés P. Mariño, Ranjit Manchanda
    Abstract:

    Longitudinal CA125 algorithms are the current basis of Ovarian Cancer Screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual Screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-Ovarian Cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-Ovarian Cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in Ovarian Cancer Screening of postmenopausal women.

  • Abstract CT104: Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial
    Lancet (London England), 2015
    Co-Authors: Ian Jacobs, Usha Menon, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Alistair Mcguire, Mahesh K. B. Parmar, Steven J. Skates
    Abstract:

    Background: Ovarian Cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of Ovarian Cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in Screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of Screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of Screening. One intervention arm of this trial was designed to establish the effect of early detection by Screening with blood tests on Ovarian Cancer mortality. We estimated its impact on cases arising after Screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal Screening (MMS) with serum CA125 interpreted with use of the risk of Ovarian Cancer algorithm, annual transvaginal ultrasound Screening (USS), or no Screening, in a 1:1:2 ratio. The primary outcome was death due to Ovarian Cancer by Dec 31, 2014, comparing MMS with no Screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have Ovarian Cancer, or had exited the registry before recruitment. For this report, we focused on the impact of Screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no Screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual Screening episodes. At a median follow-up of 11.1 years, we diagnosed Ovarian Cancer in 968 women: 338 in the MMS group, and 630 in the no Screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no Screening group had died of Ovarian Cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from Ovarian Cancer of MMS versus no Screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to Ovarian Cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of Screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS Screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of Ovarian Cancer Screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.

  • Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
    BMC public health, 2015
    Co-Authors: Katharine Bailey, Ian Jacobs, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, M Parmar, Hynek Pikhart
    Abstract:

    Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality.

  • Ovarian Cancer Screening—Current status, future directions
    Gynecologic oncology, 2013
    Co-Authors: Usha Menon, Michelle Griffin, Aleksandra Gentry-maharaj
    Abstract:

    Evidence of a mortality benefit continues to elude Ovarian Cancer (OC) Screening. Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial which used a Screening strategy incorporating CA125 cut-off and transvaginal ultrasound has not shown mortality benefit. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is using the Risk of Ovarian Cancer (ROC) time series algorithm to interpret CA125, which has shown an encouraging sensitivity and specificity however the mortality data will only be available in 2015. The article explores the impact of growing insights into disease aetiology and evolution and biomarker discovery on future Screening strategies. A better understanding of the target lesion, improved design of biomarker discovery studies, a focus on detecting low volume disease using Cancer specific markers, novel biospecimens such as cervical cytology and targeted imaging and use of time series algorithms for interpreting markers profile suggests that a new era in Screening is underway.

  • Concordance of National Cancer Registration with self-reported breast, bowel and lung Cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening
    British journal of cancer, 2013
    Co-Authors: Aleksandra Gentry-maharaj, Ian Jacobs, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, Mariam Habib, Aarti Sharma, M Parmar, Usha Menon
    Abstract:

    Concordance of National Cancer Registration with self-reported breast, bowel and lung Cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

Andy Ryan - One of the best experts on this subject based on the ideXlab platform.

  • Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women.
    Cancers, 2020
    Co-Authors: Aleksandra Gentry-maharaj, Jatinderpal Kalsi, Oleg Blyuss, Andy Ryan, Matthew Burnell, Chloe Karpinskyj, Richard Gunu, Anne Dawnay, Inés P. Mariño, Ranjit Manchanda
    Abstract:

    Longitudinal CA125 algorithms are the current basis of Ovarian Cancer Screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual Screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-Ovarian Cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-Ovarian Cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in Ovarian Cancer Screening of postmenopausal women.

  • Abstract CT104: Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial
    Lancet (London England), 2015
    Co-Authors: Ian Jacobs, Usha Menon, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Alistair Mcguire, Mahesh K. B. Parmar, Steven J. Skates
    Abstract:

    Background: Ovarian Cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of Ovarian Cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in Screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of Screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of Screening. One intervention arm of this trial was designed to establish the effect of early detection by Screening with blood tests on Ovarian Cancer mortality. We estimated its impact on cases arising after Screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal Screening (MMS) with serum CA125 interpreted with use of the risk of Ovarian Cancer algorithm, annual transvaginal ultrasound Screening (USS), or no Screening, in a 1:1:2 ratio. The primary outcome was death due to Ovarian Cancer by Dec 31, 2014, comparing MMS with no Screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have Ovarian Cancer, or had exited the registry before recruitment. For this report, we focused on the impact of Screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no Screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual Screening episodes. At a median follow-up of 11.1 years, we diagnosed Ovarian Cancer in 968 women: 338 in the MMS group, and 630 in the no Screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no Screening group had died of Ovarian Cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from Ovarian Cancer of MMS versus no Screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to Ovarian Cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of Screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS Screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of Ovarian Cancer Screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.

  • Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
    BMC public health, 2015
    Co-Authors: Katharine Bailey, Ian Jacobs, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, M Parmar, Hynek Pikhart
    Abstract:

    Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality.

  • Psychosocial Factors Associated With Withdrawal From the United Kingdom Collaborative Trial of Ovarian Cancer Screening After 1 Episode of Repeat Screening
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2015
    Co-Authors: Valerie Jenkins, Ian Jacobs, Usha Menon, Lesley Fallowfield, C Langridge, Andy Ryan, Jessica K. Barrett, Justine Kilkerr, Vernon T. Farewell
    Abstract:

    Objective: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) aims to establish the efficacy of 2 different Ovarian Cancer Screening schedules. The psychosocial substudy examines the psychological factors associated with the Screening program. Methods: Women aged 50 to 75 years from 16 UK gynecologic centers randomized to annual multimodal Screening or ultrasound Screening (US) groups were followed up for 7 years. Psychosocial data from women who withdrew from the study after a repeat screen were examined. Results: Sixteen percent (3499/21,733) of women requiring a repeat Screening test in addition to annual screen withdrew from the study: 12.9% (1560/12,073) from the multimodal group and 20.1% (1939/9660) from the US group. An estimated relative risk of withdrawal is 1.46 (95% confidence interval, 1.36-1.56; P

  • Psychological morbidity associated with Ovarian Cancer Screening: results from more than 23,000 women in the randomised trial of Ovarian Cancer Screening (UKCTOCS).
    BJOG : an international journal of obstetrics and gynaecology, 2014
    Co-Authors: Jane Barrett, Ian Jacobs, Usha Menon, C Langridge, Andy Ryan, Jenkins, Farewell, J Kilkerr, Lesley Fallowfield
    Abstract:

    Objective To examine the psychological sequelae associated with abnormal Screening in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Design Prospective, longitudinal randomised control trial. Setting Sixteen UKCTOCS centres. Sample Women aged 50–70 years randomised to annual multimodal Screening, ultrasound Screening or control groups. Methods Two groups were followed for 7 years: (1) a random sample (n = 1339), taken from all three study groups; and (2) an events sample (n = 22 035) of women with abnormal screens resulting in the need for repeat testing of either low or higher level intensity. Main outcome measures Patient-reported measures of anxiety (scores ranging from 20 to 80) and psychological morbidity. Results In the random sample the mean difference between anxiety scores after a repeat Screening and those following an annual Screening was 0.4 (95% CI −0.46, 1.27), and in the events sample it was 0.37 (95% CI 0.23, 0.51). The risk of psychological morbidity was only increased in the event sample for women requiring higher level repeat Screening (OR 1.28; 95% CI 1.18, 1.39). The risk of psychological morbidity in women with Ovarian Cancer was higher at both 6 weeks (OR 16.2; 95% CI 9.19, 28.54) and 6 months (OR 3.32; 95% CI 1.91, 5.77) following surgery. Conclusions Screening does not appear to raise anxiety but psychological morbidity is elevated by more intense repeat testing following abnormal annual screens, and in women after surgical treatment for Ovarian Cancer.

Matthew Burnell - One of the best experts on this subject based on the ideXlab platform.

  • Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women.
    Cancers, 2020
    Co-Authors: Aleksandra Gentry-maharaj, Jatinderpal Kalsi, Oleg Blyuss, Andy Ryan, Matthew Burnell, Chloe Karpinskyj, Richard Gunu, Anne Dawnay, Inés P. Mariño, Ranjit Manchanda
    Abstract:

    Longitudinal CA125 algorithms are the current basis of Ovarian Cancer Screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual Screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-Ovarian Cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-Ovarian Cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in Ovarian Cancer Screening of postmenopausal women.

  • Abstract CT104: Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial
    Lancet (London England), 2015
    Co-Authors: Ian Jacobs, Usha Menon, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Alistair Mcguire, Mahesh K. B. Parmar, Steven J. Skates
    Abstract:

    Background: Ovarian Cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of Ovarian Cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in Screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of Screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of Screening. One intervention arm of this trial was designed to establish the effect of early detection by Screening with blood tests on Ovarian Cancer mortality. We estimated its impact on cases arising after Screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal Screening (MMS) with serum CA125 interpreted with use of the risk of Ovarian Cancer algorithm, annual transvaginal ultrasound Screening (USS), or no Screening, in a 1:1:2 ratio. The primary outcome was death due to Ovarian Cancer by Dec 31, 2014, comparing MMS with no Screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have Ovarian Cancer, or had exited the registry before recruitment. For this report, we focused on the impact of Screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no Screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual Screening episodes. At a median follow-up of 11.1 years, we diagnosed Ovarian Cancer in 968 women: 338 in the MMS group, and 630 in the no Screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no Screening group had died of Ovarian Cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from Ovarian Cancer of MMS versus no Screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to Ovarian Cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of Screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS Screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of Ovarian Cancer Screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian Cancer Screening and mortality in the UK collaborative trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.

  • Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
    BMC public health, 2015
    Co-Authors: Katharine Bailey, Ian Jacobs, Jatinderpal Kalsi, Aleksandra Gentry-maharaj, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, M Parmar, Hynek Pikhart
    Abstract:

    Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality.

  • Concordance of National Cancer Registration with self-reported breast, bowel and lung Cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening
    British journal of cancer, 2013
    Co-Authors: Aleksandra Gentry-maharaj, Ian Jacobs, Andy Ryan, Matthew Burnell, Evangelia-ourania Fourkala, Sophia Apostolidou, Mariam Habib, Aarti Sharma, M Parmar, Usha Menon
    Abstract:

    Concordance of National Cancer Registration with self-reported breast, bowel and lung Cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

  • Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2013
    Co-Authors: Aarti Sharma, Aleksandra Gentry-maharaj, Matthew Burnell, Stuart Campbell, Nazar Najib Amso, Mourad W. Seif, Gwendolen Fletcher, Carol Brunel, Gill Turner, Rani Rangar
    Abstract:

    Objective: Transvaginal sonography (TVS) is core to any Ovarian Cancer Screening strategy. General-population Screening involves older postmenopausal women in whom Ovarian visualization is difficult because of decreasing Ovarian size and lack of follicular activity. We report on factors affecting the visualization of postmenopausal ovaries in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods: The UKCTOCS is a randomized controlled trial of 202 638 postmenopausal women with 50 639 women in the ultrasound scan arm. TVS is the primary Screening modality in the ultrasound scan arm. Age, education, ethnicity, body mass index (BMI), previous pelvic surgery, lifestyle and reproductive factors, and a personal/family history of Cancer were assessed for their effects on Ovarian visualization at the initial TVS. Results: Between 11 June 2001 and 18 August 2007, 43 867 women underwent TVS. The median age and BMI of the women were 60.6 (interquartile range (IQR), 9.9) years and 25.7 (IQR, 5.8), respectively. The right ovary was visualized in 29 297 (66.8%) and the left ovary was visualized in 28 726 (65.5%). Visualization of ovaries decreased with previous hysterectomy (odds ratio (OR) = 0.534; 95% CI, 0.504–0.567), previous tubal ligation (OR = 0.895; 95% CI, 0.852–0.940), increasing age (OR = 0.953; 95% CI, 0.950–0.956), unilateral oophorectomy (OR = 0.224; 95% CI, 0.186–0.269) and being overweight (OR = 0.918; 95% CI, 0.876–0.962) or obese (OR = 0.715; 95% CI, 0.677–0.755). Increased visualization was observed with a history of infertility (OR = 1.134; 95% CI, 1.005–1.279) and increasing age (in years) at menopause (OR = 1.005; 95% CI, 1.001–1.009). Conclusions: Several factors affect the visualization of postmenopausal ovaries. Their impact needs to be taken into consideration when developing quality assurance for Ovarian ultrasound scanning or comparing study results as their prevalence may differ between populations.