Invasive Epithelial Ovarian Cancer poses challenges in treatment, with residual disease affecting outcomes. This study evaluates survival based on residual disease diameter and systemic anti-cancer therapy in stage III-IV ovarian cancer patients. Data from Norwegian registries is analyzed to assess the impact of residual disease following cytoreductive surgery on overall survival, guiding clinical decision-making.
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Presentation Transcript
Example of modelling survival with registry data to assist with clinical decision-making Cassia B. Trewin-Nybr ten 2024 Northern European Stata Conference 10 September 2024 1
Background Invasive Epithelial Ovarian Cancer is often detected at a late stage (III- IV), when the cancer has spread from the ovaries (7 in 10 cases).1 Surgically removing all cancerous tissue may be difficult. One-third of stage III-IV patients have residual disease (RD) after cytoreductive surgery.1 1 Fortner et al, Cancer Epidemiology, 2023 3
Background Attaining 1cm of RD widely considered adequate cytoreduction. Cochrane review showed significantly better survival for no RD vs any RD, but no clear survival difference between patients with 1 vs >1 cm RD1. Studies considering more refined RD diameter than 1 vs >1 cm are limited. 1 Bryant et al, Cochrane Database, 2022 4
Current Norwegian treatment guidelines Define patients with > 1cm RD following cytoreductive surgery as high- risk of disease recurrence. Recommend additional maintenance therapy for these patients (Bevacizumab). 1 Bryant et al, Cochrane Database, 2022 5
Study aims 1. Evaluate survival of ovarian cancer patients across (categorical and continuous) residual disease diameter. 2. Evaluate residual disease and survival in the context of systemic anti-cancer therapy (SACT). 6
Material and methods Data: Cancer Registry of Norway and Clinical Registry for Gynecological Cancer Population: Stage III-IV surgically treated ovarian cancer patients (C56), < 90 years, 2013 2022 (N=1797). Follow-up: from surgery to death, emigration or 31.10.2023. Main exposure: Residual disease in the abdominal cavity following cytoreductive surgery. Outcome: Death from any cause. Covariates: Histotype, stage, age, ECOG performance status, neoadjuvant and adjuvant chemotherapy (sub-cohort). 7
surgical outcomes Statistical Analysis Excess hazard ratios and relative survival predicted from flexible parametric models (stpm2). Residual disease (RD) modelled in three ways: Dichotomously: RD versus no RD. Categorically: No RD, 0.1 0.4, 0.5 0.9, 1.0, 1.1 2.9, 3.0 20.0 cm. Continuously: Restricted cubic spline with 3 df and boundary knots at 0.2 and 2.0cm due to sparse data outside this range (rcsgen). 8
Excess mortality by residual disease status, 20132022 (N=1797) Residual disease (RD) Cases/ deaths EHR (95% CI) P-value Model 1: Dichotomous RD1, N=1797 No residual disease 1154 / 470 1 (ref) Residual disease 643 / 481 2.62 (2.27 3.01) < 0.001 Model 2: Categorical RD1,2, N=1653 No residual disease 1154 / 470 1 (ref) 0.1 0.4 cm 138 / 86 2.09 (1.63 2.68) < 0.001 0.5 0.9 cm 89 / 69 2.97 (2.26 3.89) < 0.001 1.0 cm 102 / 83 2.74 (2.13 3.53) < 0.001 1.1 2.9 cm 94 / 61 3.10 (2.32 4.13) < 0.001 3.0 20 cm 78 / 59 2.75 (2.05 3.70) < 0.001 1Adjusted for histotype, stage, age and ECOG performance status. 2Excluded N=52 women with unknown residual disease diameter. 9
Predicted 3-year relative survival Residual disease diameter (N=501) Relative survival predicted for women with stage III EOC, median age 64 years and fully active ECOG. Residual disease modeled continuously with a restricted cubic spline (3 df, boundary knots at 0.2 and 2.0 cm). 10
Excess mortality by neoadjuvant chemotherapy and residual disease, 2019 2022 (N=645) Cases/ deaths EHR (95% CI) P-value Primary surgery and adjuvant chemotherapy, N=350 No residual disease 266 / 44 1 (ref) < 0.001 0.1 0.9 cm 33 / 18 8.72 (4.59 16.55) 0.181 1.0 cm 14 / 6 1.99 (0.73 5.46) < 0.001 1.1 20.0 cm 37 / 15 3.64 (1.87 7.10) High-risk patients indicated for Bevac- izumab Neoadjuvant chemotherapy and interval surgery, N=295 No residual disease 216 / 61 1 (ref) 0.1 0.9 cm 38 / 18 2.09 (1.18 3.71) 0.012 1.0 cm 13 / 10 3.81 (1.83 7.92) < 0.001 1.1 20.0 cm 28 / 12 3.00 (1.45 6.19) 0.003 Adjusted for histotype, stage, age, ECOG performance status and adjuvant Bevacizumab or PARP-inhibitor treatment 11
Conclusion Best survival with no residual disease after surgery. No significant difference in survival across continuous diameter of residual disease, in the context of modern ovarian cancer treatment. All stage III-IV patients with residual disease after surgery should be considered high risk of recurrence and death, when planning adjuvant treatment. 12
Thank you to my colleagues Project initative: Ren e Turzanski Fortner Co-authors: Torbj rn Paulsen Sigrid Leithe Hilde Langseth 13
