Browsing Over 107 Presentations
Live Q&A
- Carien L. Creutzberg (Leiden, Netherlands)
13P - Dosimetric comparisons of brachytherapy applicators used in carcinoma cervix and their utility in toxicity prediction
- Naren Gokulanathan (Puducherry, India)
Abstract
Background
Brachytherapy is an important component in management of cervical cancer, enabling dose escalation with reasonable limitation of toxicity. However, in some patients, there is an inadvertent increase in OAR (Organs at Risk) doses. In our study, we analyse the dosimetric differences between the two commonly used ICBT (Intracavitary Brachytherapy) applicators in our hospital.
Methods
We performed a retrospective analysis of intracavitary brachytherapy (ICBT) plans using clinical records of 109 cervix cancer patients from Aug-2020 to Aug-2021. Patients who completed the ICBT course with the same applicators were chosen. 3 month follow up and symptom data was acquired from clinical records. The mean doses per patient were compared between FSD (Fletcher Suit Delclos) and Ring-Tandem applicator with ring cap.
Results
Ring and Tandem applicator was used in 67 patients while the Fletcher Suit Delclos applicator was used in 42 patients. The mean bladder D2cc (Highest irradiated 2cc area), rectum D2cc were 79.2% vs 79.2% and 50.4% vs 63.2%. (σ = 19.4) The mean (Posterior Inferior Border of Pubic Symphysis) PIBS +2 and PIBS dose was 146% vs 218.5% and 49% vs 83.6%. At the time of 3 months of follow up, incidence of Grade 2 dysuria was compared (0.5% v 19.5%, p<0.05) Analysing the anatomical parameters, the AP pelvic diameter correlated negatively with the average D2cc of OARs. The rectum volume correlated positively with D2cc rectum (ρ, correlation coefficient = 0.44). The rectum (ρ = 0.01) and bladder diameter (ρ = 0.15) at the level of the flange also correlated positively with OAR D2cc.
Conclusions
It can be inferred from the study that the ring and tandem has a comparably favorable dosimetric profile and it should be evaluated further, with a view to decrease OAR toxicities and improve symptom free quality of life. The dose at PIBS should also be looked into further as a marker of vaginal toxicity and urethral toxicity, and brachytherapy dose delivery should be optimised accordingly.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
50P - Direct-acting oral anticoagulants prescribing pattern in patients with gynaecological cancer: results of a survey among Italian oncologists belonging to MITO group and AIOM society
- Valentina Tuninetti (Turin, Italy)
Abstract
Background
Venous thromboembolism (VTE) is a major cause of death and morbidity in patients with cancer. Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOAC) have shown efficacy and safety not inferior to LMWH and most recent guidelines included DOACs as an option for the CAT treatment.
Methods
The aim of the survey was to better understand the prescription trends of DOACs in patients with cancers in Italy, especially gynaecological cancers (GCs). The survey was made of 21 questions and the last 4 questions were addressed to doctors involved in Gynecological Oncology. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members on 13 October 2021 and 14 October 2021, respectively. Respondents completed the survey by 15 November 2021.
Results
Overall, 113 medical doctors (MDs) completed the questionnaire and 69 of them were involved in Gynecological Oncology. Most of the respondents (46, 41%) were aged 30-40 years old, worked in a Public Hospital (59, 52.2%), were Medical Oncologists (86, 76.1%) and, at the time of the survey, were not allowed by Italian Regulations to prescribe a DOAC (108, 96%). LMWH was widely the preferred choice for the treatment of CAT (104, 92%). However, 89 (78.8%) of the respondents stated that they had prescribed or asked another specialist to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty to verify the therapeutic effect/absence of antidotes in case of severe bleeding (37.9%). In patient with GCs, DOACs were used with Niraparib, Olaparib and Rucaparib in less than 10 patients by 23%, 20% and 9% of the respondents, respectively. They seemed to be more confident in the use of immune checkpoint inhibitors (ICIs) with a DOAC, indeed 10.2% (7/69) have employed them in more than 10 patients.
Conclusions
DOACs are still poorly prescribed in patients with cancer, especially for GCs.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Future clinical research and unmet needs
- Isabelle L. Ray-Coquard (Lyon, France)
Q&A from audience
- The Panelists (Valencia, Spain)
8P - 20 years of cervical cancer screening program and the impact on hospitalization rates in the public health system in a state of Brazil
- Ana Maria F. Silva (Aracaju, Brazil)
Abstract
Background
Cervical cancer is one of the leading causes of death by neoplasia in the world. In Brazil, it is the 3rd cause of women's death by neoplasia. Since its implantation, 20 years ago, the federal program to prevent cervical cancer frequently had logistic and technical difficulties, especially in remote areas. Morbimortality studies are necessary to evaluate the evolution of the prevention program.
Methods
The present study evaluated cervical cancer hospitalizations in the state of Sergipe between 2008 and 2015. The data was extracted from a public database containing information about the unified public health system. The variables age, city of residence and type of hospitalization (clinical or surgical) were analyzed. Changes in hospitalization rates after the introduction of Papanicolaou test as a priority in primary care were considered through a temporal analysis using Joinpoint regression software. For this purpose, it was devised a linear logarithmic model that includes points and calculate the difference from a statistically significant value using a Monte-Carlo permutation test. The Average Annual Percent Change (AAPC), Annual Percent Change (APC) and temporal tendencies in hospitalization frequencies were calculated.
Results
873 hospitalizations were analyzed, the median age was 46 years. Surgical hospitalizations correspond to 67%.The temporal analysis showed a yearly decrease in hospitalizations of about 10%, both for the population living in the capital and in other cities of the state. When the hospitalizations in the whole state were divided by age subgroups, there was a statistically significant reduction in the subgroups 40 to 59 years and 60 years or more.
Conclusions
A consistent reduction in cervical cancer hospitalizations was observed in the state of Sergipe in the analyzed time period. This suggests an improvement after 20 years of the cervical cancer prevention program. Better access to diagnostic methods and appropriate treatment allow for more effective interventions, with fewer hospitalizations. There is, however, a long way to go, especially with regard to expanding health care for the population across the state, also aiming at reducing mortality rates.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
44TiP - ENGOT-ov65/KEYNOTE-B96: Phase 3, randomized, double-blind study of pembrolizumab vs placebo + paclitaxel with optional bevacizumab for platinum-resistant recurrent ovarian cancer
- Nicoletta Colombo (Milan, Italy)
Abstract
Background
There is an urgent need for new treatments for platinum-resistant recurrent ovarian cancer (PROC). Addition of bevacizumab (bev) to non-platinum-based chemotherapy (chemo) significantly improved PFS in patients (pts) with PROC but did not show a clear OS benefit. Thus far, the combination of paclitaxel + bev has shown the most promise in PROC, although the proportion of pts eligible for bev is limited by treatment-related toxicities. Combination of the anti-PD-1 antibody pembrolizumab (pembro) with weekly paclitaxel showed antitumor activity and manageable toxicity in pts with PROC in a single-arm, phase II study. ENGOT-ov65/KEYNOTE-B96 (NCT05116189) compares the efficacy and safety of pembro + standard of care chemo (weekly paclitaxel) ± bev vs placebo (pbo) + weekly paclitaxel ± bev in pts with PROC.
Trial design
In this randomized, pbo-controlled, double-blind, phase III study, eligible pts are aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-2 prior lines of systemic therapy, including ≥1 prior platinum-based therapy with ≥4 cycles in first line. Pts must have platinum-resistant disease (radiographic evidence of PD ≤6 mo after last platinum-based therapy dose), be eligible for paclitaxel (± bev per investigator discretion), have ECOG PS ≤1, radiographically evaluable disease per RECIST v1.1, and have a tumor sample for central evaluation of PD-L1 status. ∼616 pts will be randomized 1:1 to pembro 400 mg IV or pbo Q6W for up to 18 cycles (∼2 y) + paclitaxel 80 mg/m2 on days 1, 8, and 15 of each Q3W cycle (± bev 10 mg/kg Q2W per investigator discretion) until PD or unacceptable toxicity. Randomization is stratified by planned bev use (yes vs no), region (US vs Europe vs rest of world), and PD-L1 status (combined positive score [CPS] <1 vs CPS 1-<10 vs CPS ≥10). Primary endpoint is PFS per RECIST v1.1 by investigator review in pts with tumor PD-L1 CPS ≥1 and in all pts. Secondary endpoints are OS in pts with tumor PD-L1 CPS ≥1 and in all pts, PFS per RECIST v1.1 by blinded independent central review in pts with tumor PD-L1 CPS ≥1 and in all pts, safety, and pt-reported outcomes. Enrollment is ongoing.
Clinical trial identification
NCT05116189.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
N. Colombo: Financial Interests, Personal, Full or part-time Employment, Employment of Immediate Family Member: Sarepta Therapeutics; Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Tesaro, GlaxoSmithKline, Immunogen, Mersana, Eisai, Advaxis, Nuvation Bio, Advaxis; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer, Mersana, Eisai, Advaxis, Nuvation Bio. R.L. Coleman: Financial Interests, Personal, Full or part-time Employment: US Oncology; Financial Interests, Personal, Advisory Role: Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, Tesaro, OncoMed, Sotio, Oncolytics, AbbVie/Stemcentrx, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, Regeneron; Financial Interests, Personal, Leadership Role: Onxeo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Sotio, Vaniam Group; Financial Interests, Personal, Stocks/Shares: McKesson; Financial Interests, Personal, Ownership Interest: McKesson; Financial Interests, Personal, Research Grant: AstraZeneca/MedImmune, Esperance Pharmaceuticals, Array Biopharma, Clovis Oncology, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie; Financial Interests, Institutional, Research Grant: Immunogen, Mirati Therapeutics, Amgen, Pfizer, Lilly, Regeneron. F. Kose: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Institutional, Other, Honoraria: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen. R. Wenham: Financial Interests, Personal, Advisory Role: Mersana, Merck, Tesaro, Clovis Oncology, Genentech, Regeneron, AbbVie, AstraZeneca, GlaxoSmithKline, Seattle Genetics/Astellas, Legend Biotech; Financial Interests, Personal, Speaker’s Bureau: Tesaro, Clovis Oncology, Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: TapImmune Inc; Financial Interests, Personal, Stocks/Shares: Ovation Diagnostics; Financial Interests, Personal, Ownership Interest: Ovation Diagnostics; Financial Interests, Personal, Other, Honoraria: Tesaro, Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck, Prescient Therapeutics, Anixa Biosciences. Other Relationship: AstraZeneca, GlaxoSmithKline/Tesaro; Other, Personal, Other: AstraZeneca, GlaxoSmithKline/Tesaro. A. Sebastianelli: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, GlaxoSmithKline. K. Hasegawa: Financial Interests, Personal, Advisory Role: MSD K.K., Kaken Pharmaceutical, Eisai, Takeda; Financial Interests, Personal, Other, Honoraria: MSD K.K., Daiichi Sankyo, Chugai Pharma, AstraZeneca, Eisai, Kyowa Kirin, Takeda, Genmab; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Daiichi Sankyo, Merck, Takeda, Eisai. E. Zsiros: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, Honoraria: Survivornet, AstraZeneca, TeneoBio; Financial Interests, Personal, Research Grant: Merck. T. De La Motte Rouge: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Personal, Advisory Role: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Seagen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, French National Cancer Institute (INCa). M. Bidzinski: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, GlaxoSmithKline, Johnson & Johnson, Olympus. I. McNeish: Financial Interests, Personal, Advisory Role: Clovis Oncology, AstraZeneca, Carrick Therapeutics, Roche, BeiGene, Scancell Ltd., GlaxoSmithKline, Epsila; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. J. Sehouli: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche, Ingress Health, Riemser, Sobi, GlaxoSmithKline, Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GlaxoSmithKline, Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. J. Korach: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P.R. Debruyne: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Stocks/Shares: Alkermes, Biocartis Group NV; Financial Interests, Personal, Ownership Interest: Alkermes, Biocartis Group NV; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Merck/Pfizer, MSD, Roche, Bayer. J. Kim: Financial Interests, Personal, Advisory Board: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea; Financial Interests, Personal, Invited Speaker: CMIC, AstraZeneca, Janssen; Financial Interests, Personal, Expert Testimony: LG Pharma. A.C. De Melo: Financial Interests, Personal, Speaker’s Bureau: BMS Brazil, MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Novartis, BMS Brazil; Financial Interests, Institutional, Research Grant: Roche, MSD Oncology, BMS Brazil, Novartis, Clovis Oncology, AstraZeneca. X. Peng: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A.M. Bogusz: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. K. Yamada: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. B.J. Monk: Financial Interests, Personal, Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesa; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GlaxoSmithKline, Merck; Financial Interests, Personal, Other, Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesaro/GlaxoSmithKline, Vascular Biogenics; Financial Interests, Institutional, Research Grant: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana. All other authors have declared no conflicts of interest.
Management of immunotherapy and targeted therapies-induced toxicities
- Antonio Jose Gonzalez Martin (Madrid, Spain)
Recent advances in the management of endometrial cancer
- Ana Oaknin (Barcelona, Spain)
3P - Identification of novel biomarkers of response to ATR inhibitors in ARID1A mutant ovarian clear cell carcinoma.
- James R. Stewart (London, United Kingdom)
Abstract
Background
Ovarian clear cell carcinoma (OCCC) is characterised by a high prevalence of ARID1A mutations and chemotherapy resistance. We previously found that loss of ARID1A causes ATR inhibitor (ATRi) sensitivity, which led to the phase II ATARI clinical trial (NCT04065269). We aim to identify novel genetic determinants of ATRi response in ARID1A-mutant OCCC.
Methods
A genome wide CRISPR knockout (CRISPRn) screen was performed in OCCC TOV21G cells. CRISPR prime gene-editing was used to introduce PPP2R1A p.R183 mutations. In vitro and in vivo ATRi sensitivity was assessed in PPP2R1A isogenic models. Cell cycle analysis was performed via flow cytometry. Phospho-proteomic profiling was performed using mass spectrometry.
Results
A CRISPRn screen in ARID1A mutant OCCC cells identified protein phosphatase 2 (PP2A) complex subunits as ATRi response genes. In OCCC, PPP2R1A missense mutations cause amino acid substitutions at residue p.R183. Characterisation of a cohort of OCCC primary tumours revealed a higher prevalence of structural subunit (PPP2R1A) mutations than previously reported (50%) which frequently co-occurred with ARID1A mutations. ARID1A-mutant OCCC cells with heterozygous PPP2R1A p.R183P or p.R183W mutations displayed enhanced ATRi sensitivity in vitro and in vivo. The most profound cell-cycle defect caused by PPP2R1A missense mutation was an ATRi-induced reduction in active S phase. ATRi exposure in PPP2R1A mutants increased 53BP1 bodies, a mark of residual DNA damage in mitosis. Phospho-proteomic profiling of PPP2R1A mutant OCCC cells revealed the selective increase in phosphorylation of Lysine Deficient Protein Kinase 1 (WNK1) following ATRi exposure, as well as increased phosphorylation of the WNK1 substrate Oxidative Stress Response Kinase 1 (OSR1). Depletion of WNK1 rescued ATRi sensitivity and S phase defects in PPP2R1A mutant cells suggesting a novel role for this kinase.
Conclusions
The ability of PPP2R1A missense mutations to enhance ATRi sensitivity in tumours cells with pre-existing ARID1A mutations suggests that the co-occurrence of these mutations may be better predictors of ATRi sensitivity than either mutation alone. Increased phosphorylation of WNK1 may drive ATRi sensitivity in PPP2R1A mutant cells.
Legal entity responsible for the study
The authors.
Funding
Cancer Research UK.
Disclosure
S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Genmabs; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Oxcerna; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Shattuk Labs; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Immunogen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Mersana; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche. C. Lord: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: KGaG; Financial Interests, Institutional, Research Grant: Artios; Financial Interests, Personal, Advisory Board: Syncona; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal, Advisory Board: Gerson Lehrman; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Vertex; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Dark Blue Therapeutics; Financial Interests, Personal, Stocks/Shares: Tango; Financial Interests, Personal, Stocks/Shares: Ovibio; Financial Interests, Personal, Stocks/Shares: Enedra Tx; Financial Interests, Personal, Stocks/Shares: Hysplex; Financial Interests, Personal, Stocks/Shares: Tesselate. All other authors have declared no conflicts of interest.
39P - Longitudinal Increases in Albumin-Adjusted Serum Calcium Predict Ovarian Cancer
- Gary Schwartz (Grand Forks, ND, ND, United States of America)
Abstract
Background
Screening methods for ovarian cancer are urgently needed. Previously, we showed that women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin (Schwartz et al, 2020, Gynecol Oncol 2020:159:264-269). These changes could be useful in screening. We asked, prior to their diagnosis, are women with ovarian cancer more likely to show a positive slope in their in albumin-adjusted serum calcium (a-asc)?
Methods
This is a population-based case-control study based in Sioux Falls, SD. Cases were women with epithelial ovarian cancer. Controls are women without a diagnosis of cancer. Patients with a history of cancer and/or parathyroid disease were excluded. Data are from patients’ Comprehensive Metabolic Panels (CMPs). We calculated albumin-adjusted serum calcium (a-asc) and estimated regression equations of each woman’s a-asc from pre-diagnosis to diagnosis. Data were analyzed by multiple regression, ANCOVA and logistic regression.
Results
We studied 124 cases and 98 controls. Cases were significantly older than controls (64.7 12.9 SD, vs. 41.0 16.8 years). For controls, the first and last a-asc was 9.23 mg/dL, for a slope of 0. For cases, the first and last values of a-asc were 9.28 and 9.37 mg/dL, for a slope of 0.04 mg/dl per year (P<0.001). The probability of cancer for a 0.04 mg/dL/year increase in a-asc increased with age until age 70 and showed a significant dose-response. The Odd Ratio (OR) of ovarian cancer for a 65 yr old woman with a 0.06 mg/dL increase/year was ∼3.0; the OR for a 1 mg/dl increase/year was ∼10. This effect was also seen for early stage tumors and persisted after age-adjustment.
Conclusions
In health, serum calcium levels are tightly regulated and the “expected” slope of a-asc is zero. A significant positive slope of a-asc in women with ovarian cancer, if confirmed by future studies, suggests that an increase in the slope a-asc could help identify women with undiagnosed ovarian cancer. Increases in a-asc were often small and could be easily overlooked. However, a computer algorithm could calculate the slope from patients’ annual records. Women with rising a-asc could be candidates for increased medical surveillance (e.g., transvaginal ultrasonography).
Legal entity responsible for the study
The authors.
Funding
This research was funded by grants from the University of North Dakota School of Medicine & Health Sciences, the Great Plains IDeA-CTR and the Coverys Community HealthCare Foundation (to GGS).
Disclosure
All authors have declared no conflicts of interest.
28MO - Real-world whole sequencing data of ovarian cancer patients
- James D. Brenton (Cambridge, United Kingdom)
Abstract
Background
Poly(ADP-ribose)-polymerase (PARP) inhibitor therapy has dramatically changed outcomes for women with high-grade serous ovarian carcinoma. Germline or somatic pathogenic variants in BRCA1 or BRCA2 are strong predictive biomarkers for PARP therapy, but patients with other causes of homologous recombination deficiency (HRD) also strongly benefit. NHS patients have commercial testing for HRD using the Myriad MyChoice assay, but using WGS through the GLH could provide a more cost-effective and universally accessible assay for NHS patients.
Methods
We compared the performance of 3 bioinformatics algorithms for HRD detection (CHORD, HRDetect, Dragen) for ovarian cancer patients included in the 100K dataset to perform real-world response and survival analysis.
Results
HRD was associated with better overall survival outcome across all 3 algorithms in patients treated with platinum-based therapy (CHORD: n=259, HR=0.32 [95% CI 0.19–0.52], Wald test=20.94, p«0.001; Dragen: n=268, HR=0.38 [95% CI 0.23–0.62], Wald test=14.9, p<0.001; HRDetect: n=239, HR=0.28 [95% CI 0.16–0.48], Wald test=21.24, p«0.001). The results of the analysis showed substantial concordance, both in between each bioinformatics algorithm and in correlation with the BRCA1/2 status. However, for accurate correlation of the WGS-based HRD scores with the measures of response, there is a prerequisite of high-quality clinical data.
Conclusions
Clinically relevant HRD prediction is feasible using WGS data and supports further development of these algorithms for NHS use in the Genomics Medicine Service. Future improvements will use a multimodal machine-learning (ML) model to define separate weights for classes of clinical data or genomic data (HRD) and subclasses of data points. We will also include multimodal data as additional covariates in the models, including radiomic and pathology image analysis data. Incorporating multi-dimensional data, in particular pathology and radiological imaging parameters, into an ML model is fundamental for improved integrative biomarkers of HRD.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.D. Brenton: Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Tailor Bio; Financial Interests, Personal, Stocks/Shares: Tailor Bio; Financial Interests, Institutional, Invited Speaker: Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Aprea AB; Non-Financial Interests, Personal, Member: Association of Cancer Physicians. All other authors have declared no conflicts of interest.