Annika Auranen

Implementation of extensive cytoreductive surgery protocol in advanced epithelial ovarian cancer: Real‐world data on surgical treatment distribution and survival of the whole patient cohort; a single center experience

AbstractIntroductionThe aim was to assess the effect of the implementation of maximal surgical cytoreduction on the treatment decisions and overall survival of the entire patient cohort with advanced epithelial ovarian cancer.Material and MethodsWe collected retrospectively all newly diagnosed patients with FIGO stage IIIB–IVB epithelial ovarian cancer between 2013 and 2019 in Tampere University Hospital, Finland. Altogether, 333 patients were divided into two groups based on the date of diagnosis: Group 1 (n = 162) diagnosed before March 2016 and Group 2 (n = 171) after 1st of March 2016, when a systematic change in surgical approach toward maximal surgical cytoreduction was implemented in our institution.ResultsNo statistically significant differences were found in the proportions of patients having surgery or treated non‐surgically between the two time periods: 76.5% of patients in Group 1 and 71.9% in Group 2 underwent surgical treatment, while the others were treated with chemotherapy only or referred directly to palliative care (p = 0.38). In addition, there was no statistically significant difference in overall survival in patients who received any treatment (surgery and chemotherapy or chemotherapy only) between groups: the median overall survival was 32.8 months (95% CI 25.1–40.5) in Group 1 and 37.3 months (31.5–43.1) in Group 2, p = 0.214.ConclusionsThe change in surgical approach toward maximal surgical cytoreduction in advanced epithelial ovarian cancer did not significantly change the magnitude of patients who received only chemotherapy or underwent surgical treatment in our center. While the shift in surgical paradigm may provide survival benefits for carefully selected surgically treated patients, it did not result in a statistically significant improvement in overall survival for the entire patient cohort.

Sensitive circulating tumor DNA–based residual disease detection in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)–based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63,P< 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22,P< 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479–1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.

Long‐term risk of cancer among the first‐degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up

AbstractIntroductionThe long‐term risk of cancer among first‐degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers.Material and methodsUsing registry data, we conducted a retrospective cohort study with a total of 6501 first‐degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach).ResultsThe overall number of cancers was not increased among the first‐degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27–2.79), mostly explained by a 2.30‐fold (95% CI 1.46–3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient.ConclusionsIn our study cohort, we did not observe an increase in the overall cancer risk among the first‐degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.

Maximal surgical effort increases the risk of postoperative complications in the treatment of advanced ovarian cancer

Surgery is the cornerstone of the treatment for advanced ovarian cancer. Reaching complete cytoreduction resulting in no gross residual disease often requires complex surgery. The aim of this study was to assess the impact of increased surgical radicality on the risk of complications in the treatment of advanced ovarian cancer. All consecutive patients with advanced ovarian cancer (FIGO Stage IIIB-IVB) who had undergone primary or interval debulking surgery during a six-year study period were identified. In the midst of the study period, a surgical practice change towards maximal surgical effort occurred. Two groups were formed for the analysis: cohort A, that consisted of patients operated before the surgical paradigm shift and cohort B, that consisted of patients operated under the period of increased surgical radicality. 252 patients were included in the analysis. Complete resection (R0) was achieved in 21.3% of surgeries in cohort A and in 51.2% in cohort B. The total postoperative complication rate was 76.2%. Most of the complications (86.5%) were minor (Clavien-Dindo I-IIIA). The patients in cohort B were at increased risk for complications, OR 2.94 (95%CI 1.58-5.47; p = 0.001). As for the approach to cytoreduction (primary vs. interval debulking), there was no statistically significant association with the occurrence of postoperative complications (p = 0.659). In the present study more extensive surgeries led to better surgical results but increased postoperative morbidity. Postoperative complication rates were similar in both primary and interval debulking surgeries.

Real-life treatment patterns and time to next treatment among patients with ovarian cancer in the pre-PARP inhibitor era: the OCRWE-Finland Study

Background: As the treatment landscape for advanced ovarian cancer (OC) evolves, it is important to understand patient outcomes in real-world clinical practice. OCRWE-Finland was an observational cohort study investigating OC outcomes, including treatment patterns, time to next treatment 1 (TTNT1), overall survival and healthcare resource utilisation, in Finland during the pre-PARPi era. Materials and methods: Patients included in OCRWE-Finland were diagnosed with OC between 2014 and 2019. Here, we report treatment patterns and TTNT1 outcomes (as a surrogate for progression-free survival) for patients in the high-grade serous ovarian carcinoma (HGSOC) cohort. Results: In OCRWE-Finland, there were 867 patients with HGSOC. Of the 811 patients who received first-line treatment, the most common regimen was surgery and adjuvant chemotherapy (53%), and 227 patients also received first-line bevacizumab. Median TTNT1 among 623 patients with stage III/IV disease was 19 months (95% confidence interval, 18–21 months), with no difference between patients with stage III or IV disease (p = 0.24). The presence versus absence of visible residual disease post-debulking surgery was associated with shorter TTNT1 among patients with stage III tumours (p = 0.031) but showed no impact for stage IV tumours (p = 0.55). First-line versus no first-line bevacizumab was associated with shorter TTNT1 among stages I–IV (p < 0.0001) but did not affect patients with stage III/IV tumours (p = 0.45). Interpretation: In the pre-PARPi era, prognosis for advanced OC was poor, particularly for patients with stage III tumours and visible residual disease or stage IV tumours regardless of the presence of residual disease. The increasing use of PARPis will hopefully help address the need for effective treatments in advanced OC.