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Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

The Ministry of Health Malaysia aims to fully replace liquid-based cytology (LBC) with Human Papillomavirus (HPV) tests and increase the screening coverage from a baseline of 25% to 40% by 2023, followed by a 10% yearly increment until 70% coverage. This transition requires proper planning, including the number of tests needed and budget allocation. This study aims to simulate different transition strategies involving the shift from LBC to HPV testing with expanded screening coverage to predict their impact on cervical cancer elimination in Malaysia. A system dynamics model was developed to simulate the transition from LBC to HPV testing and HPV vaccination coverage in Malaysia. The dynamic model utilised local epidemiological data, published research, and expert opinion when data was unavailable. The simulation showed that a combination of high HPV vaccination coverage and transitioning fully to five-yearly HPV testing by 2030, coupled with a 70% screening uptake by 2040, would accelerate cancer elimination in Malaysia by 18 years with an estimated screening cost of MYR1.81 billion equivalent to USD 411 millions compared to the baseline of using LBC as the primary screening method (MYR1.39 billion, USD 315 millions). Sustained, it would lead to averting 6,000 new cancer cases by 2070. Alternatively, conducting HPV screenings twice before age 50 would advance cervical cancer elimination by 14 years and prevent approximately 1000 new cases by 2070, with an estimated cost of MYR1.13 billion equivalent to USD 257 millions. A delay in achieving the full transition prolonged the elimination more than a delay in increasing the screening coverage. In all scenarios, yearly vaccination of 90% of girls age 13 is crucial to achieving elimination. In the Malaysian context, where HPV vaccination coverage has reached considerable levels, the evidence advocates for a full transition from LBC to HPV testing, ideally by 2030. While expanding screening coverage remains a critical factor in this endeavour, the findings unequivocally endorse prioritising the transition process. Trial registration: Trial registration number: NMRR ID-22-00187-DJU. [ABSTRACT FROM AUTHOR]

Krukenberg tumour is a rare clinical entity and accounts for about 1-2% of all ovarian tumours. It is a metastatic ovarian tumour in which accurate diagnosis requires proper endoscopic evaluation and histopathological confirmation to exclude primary ovarian tumours. Dextrocardia with situs inversus totalis is another unusual clinical entity, with an incidence of 1 in 10,000 of the general population. Many patients with this unusual condition are unaware of their structural abnormality and mostly are diagnosed incidentally when they present with other medical conditions. Herein, we report a case of 47 years old woman who presented with bilateral ovarian tumour and incidental diagnosis of Dextrocardia with situs inversus totalis. She underwent surgery and histopathological examination confirms Krukenberg tumour. Both conditions existing together, an exceptionally rare clinical entity. [ABSTRACT FROM AUTHOR]

Background: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming., Methods: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer., Results: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms., Conclusion: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV- 16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening, was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs., (Creative Commons Attribution License)