Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Regional disparities in the availability of cancer clinical trials in Korea.

OBJECTIVES: Unequal access to cancer clinical trials is an important issue, given the potential benefits of participation for cancer patients. We evaluated regional disparities in access to cancer clinical trials in Korea. METHODS: From the Ministry of Food and Drug Safety database, we extracted 2,465 records of all cancer clinical trials approved between January 2012 and April 2023. To measure disparities in cancer clinical trial access, we calculated the ratio of clinical trials open to non-capital areas relative to those open to capital areas. We then analyzed temporal trends in this ratio, which we termed the trial geographical equity index (TGEI). RESULTS: Disparities in access to cancer clinical trials, as indicated by the TGEI, did not significantly improve during the study period (regression coefficient, 0.002; p=0.59). However, for phase II/III trials sponsored by global pharmaceutical companies, the TGEI improved significantly (regression coefficient, 0.021; p<0.01). In contrast, the TGEI deteriorated for trials initiated by investigators or those testing domestically developed therapeutics (regression coefficient, -0.015; p=0.05). Furthermore, the increasing trend of TGEI for phase II/III trials sponsored by global companies began to reverse after 2019, coinciding with the outbreak of coronavirus disease 2019 (COVID-19). CONCLUSIONS: Over the past decade, access to cancer clinical trials has improved in Korea, particularly for phase II/III trials evaluating therapeutics from global companies. However, this increase in accessibility has not extended to trials initiated by investigators or those assessing domestically developed therapeutics. Additionally, the impact of COVID-19 on disparities in clinical trial access should be closely monitored.

Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey.

OBJECTIVE: To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. METHODS: The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. RESULTS: Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. CONCLUSION: Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Anastomotic leakage after resection of the rectosigmoid colon in primary ovarian cancer.

BACKGROUND: The aim of the study is to evaluate the risk factors of anastomotic leakage (AL) and develop a nomogram to predict the risk of AL in surgical management of primary ovarian cancer. METHODS: We retrospectively reviewed 770 patients with primary ovarian cancer who underwent surgical resection of the rectosigmoid colon as part of cytoreductive surgery between January 2000 to December 2020. AL was defined based on radiologic studies or sigmoidoscopy with relevant clinical findings. Logistic regression analyses were performed to identify the risk factor of AL, and a nomogram was developed based on the multivariable analysis. The bootstrapped-concordance index was used for internal validation of the nomogram, and calibration plots were constructed. RESULTS: The incidence of AL after resection of the rectosigmoid colon was 4.2% (32/770). Diabetes (OR 3.79; 95% CI, 1.31-12.69; p = 0.031), co-operation with distal pancreatectomy (OR, 4.8150; 95% CI, 1.35-17.10; p = 0.015), macroscopic residual tumor (OR, 7.43; 95% CI, 3.24-17.07; p = 0<001) and anastomotic level from the anal verge shorter than 10 cm (OR, 6.28; 95% CI, 2.29-21.43; p = 0.001) were significant prognostic factors for AL on multivariable analysis. Using four variables, the nomogram has been developed to predict anastomotic leakage: https://ALnomogram.github.io/ . CONCLUSION: Four risk factors for AL after resection of the rectosigmoid colon are identified from the largest ovarian cancer study cohort. The nomogram from this information provides a numerical risk probability of AL, which could be used in preoperative counseling with patients and intraoperative decision for accompanying surgical procedures and prophylactic use of ileostomy or colostomy to minimize the risk of postoperative leakage. TRIAL REGISTRATION: Retrospectively registered.

A predictive model based on site-specific risk factors of recurrence regions in endometrial cancer patients.

OBJECTIVE: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated. METHODS: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. RESULTS: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. CONCLUSION: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients.

Surgical outcomes of ureteral reconstruction during cytoreductive surgery for ovarian cancer: a retrospective cohort study.

BACKGROUND: Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer.  METHODS: A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis.  RESULTS: Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4-9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. CONCLUSIONS: Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. TRIAL REGISTRATION: Retrospectively registered.

Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing: A Korean Gynecologic Oncology Group study (KGOG 3047).

Through the wide adaptation of next-generation sequencing (NGS) technology within clinical practice, molecular profiling of the tumor has been the principal component of personalized treatment. In our study, we have generated a large collection of cancer genomes on East Asian epithelial ovarian carcinoma (EOC) patients and demonstrate the feasibility and utility of NGS platforms to explore the dynamic interrelations of major cancer driver alterations and their impacts on clinical prognosis and management. A total of 652 EOC patients have undergone clinical NGS panels to determine the prevalence of germline and somatic mutations. Notably, TP53 was the most frequently altered event (73%), followed by both BRCA1 and BRCA2 (22% each) and MYC (19%) through pan-EOC analysis. When analyzed based on individual histopathological levels, TP53 mutation was highly dominant in high-grade serous and mucinous histology, whereas mutations in PIK3CA and ARID1A were mostly observed in clear cell carcinoma, and KRAS, BRAF, and CDKN2A mutations were enriched in endometrioid, low-grade serous, and mucinous tumors, respectively. The network-based probabilistic model showed significant co-occurrences of TP53 with BRCA1 and ALK with BRCA2, NOTCH1, and ROS1, whereas mutual exclusivity of TP53 with KRAS and PIK3CA was evident. Furthermore, we utilized machine-learning algorithms to identify molecular correlates that conferred increased sensitivity to platinum and olaparib treatments including somatic mutations in BRCA1, ATM, and MYC. Conversely, patients with ALK mutation were considerably resistant to both treatment modalities. Collectively, our results demonstrate the clinical feasibility of prospective genetic sequencing to facilitate personalized treatment opportunities for patients with EOC.

Health-Related Quality of Life of Patients with Cervical Cancer According to the Duration of Treatment and Cancer Progression.

OBJECTIVE: The purpose of this study was to assess health-related quality of life (HRQoL) in Korean patients with cervical cancer according to the duration of treatment and cancer progression of cervical cancer. METHODS: This study included 452 outpatients with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer from six tertiary hospitals in South Korea. The questionnaire included the EQ-5D-3L instrument, patients' age, cancer progression (CIN or invasive cervical cancer), treatment duration (<1 year, ≥1 year but <2 years, and ≥2 years), treatment method (surgery, chemotherapy, radiation therapy), and presence of recurrence. HRQoL indices were calculated for these independent factors, and the mean was compared using ANOVA. Multiple regression analysis was performed to analyze factors affecting HRQoL in patients with cervical cancer. RESULTS: The EQ-5D index was 0.93 for patients with CIN, 0.87 for patients with invasive cervical cancer, and 0.78 for patients with recurrent invasive cervical cancer. HRQoL was significantly lower as the CIN progresses to cervical cancer. HRQoL of patients with invasive cervical cancer was lowest within 1 year of treatment in all stages. In addition, the HRQoL of patients with CIN or invasive cervical cancer who received chemotherapy and radiotherapy was lower than that of patients who underwent surgery. Multiple regression analysis showed that the HRQoL decreased significantly as increasing age, the first year of treatment after diagnosis, cancer recurrence, or chemotherapy. CONCLUSION: The HRQoL of patients with cervical cancer is affected not only by the stage of cancer progression but also by the duration of treatment and the type of treatment. As a result, when trying to apply the quality of life of patients with cervical cancer to cost-utility analysis, it is necessary to consider the duration and the type of treatment they receive.

Randomized multicenter phase II trial of prophylactic irradiation of para-aortic lymph nodes in advanced cervical cancer according to tumor hypoxia: Korean Radiation Oncology Group (KROG 07-01) study.

We conducted a prospective phase II study on whether extended-field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA-seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5-year para-aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease-free survival (DFS; 78% vs 70%, P = .066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)-only positive, CA9/hypoxia-inducible factor (HIF) double positive and CA9 negative. In the CA9-only positive, EFI successfully increased 5-year PARFS (100% vs 76.4%, P = .010), resulting in significantly improved long-term DFS (85.7% vs 54.7%, P = .023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA-seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = -.37, P < .01), which showed a higher 5-year DFS than the immunelow (P = .032). Hypoxia-related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P < .05). Only 17.4% of patients in CA9-negative group showed immunelow signatures, while 40.0% of patients in the double-positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9-only positive LAUCC, and not in CA9/HIFs double-positive subgroup. RNA-seq analysis suggested that hypoxia-induced immunosuppression may be related to treatment resistance in LAUCC.

How Do Patients Value the Benefit of Minimally Invasive Surgery in Cancer Treatment?

OBJECTIVES: Due to the increasing cost of cancer treatment, the demand for value-based healthcare is increasing. Although several value frameworks have been developed recently in the field of oncology, the nononcological benefits of minimally invasive surgery have not been addressed. This study aimed to estimate how patients value nononcological benefits in minimally invasive cancer surgery. METHODS: The value that patients placed on various benefits of cancer surgery was termed throughout the study as patient value (PV). To quantize PVs for the benefits of cancer surgery, a one-tiered analytic hierarchy process model was constructed. The model includes 6 well-known surgical outcomes, including nononcological benefits. The study participants included 303 patients with cancer and family caregivers who participated in a questionnaire survey. RESULTS: The PVs for "decreased operation time," "reduced length of hospital stay," and "improved cosmetic results" were 0.050, 0.044, and 0.045, respectively, whereas the PVs for "increased survival," "prevention of disease recurrence," and "avoidance of complications" were 0.366, 0.292, and 0.203, respectively. The PV placed on nononcological benefits from minimally invasive surgery was one-tenth (10.2%) of the total value. CONCLUSIONS: Nononcological benefits arising from minimally invasive surgery were relatively small but nonnegligible. This value should be considered in the process of developing a value framework for cancer surgery and shared decision making.

Predicting the risk of the distant recurrence of cervical cancer after concurrent chemoradiation: A validation study of the Korean Gynecologic Oncologic Group (KGOG)-1024 model.

BACKGROUND: This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). METHODS: In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. RESULTS: The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. CONCLUSIONS: The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

Clinical outcomes of BRCA1/2 pathogenic variants in ovarian cancer cluster region in patients with primary peritoneal, epithelial ovarian, and fallopian tube cancer.

OBJECTIVE: An "ovarian cancer cluster region" (OCCR) has been reported in both BRCA1 and BRCA2. However, the clinical significance of the OCCR of BRCA1/2 has not yet been investigated. METHODS: The medical records of 991 patients with epithelial ovarian, primary peritoneal, and fallopian tube cancer who underwent genetic testing for BRCA1 and/or BRCA2 from January 1, 2006, to August 31, 2019, were retrospectively reviewed. Sanger and next-generation sequencing analyses were used to test the BRCA1 and BRCA2 mutation status. Progression-free survival (PFS) and overall survival (OS) were compared according to the mutation location (OCCR vs. non-OCCR region). Survival outcomes were determined using Kaplan-Meier survival analysis. RESULTS: A total of 162 patients had BRCA1 pathogenic variants (PVs), and 76 had BRCA2 PVs. Patients with BRCA1 PV that in the OCCR region showed shorter PFS than those with BRCA1 PV outside the OCCR (22.6 months vs. 27.6 months, P = 0.038). In the platinum-sensitive subgroup of BRCA1, patients with BRCA1 PV in the OCCR region showed shorter PFS than those in the non-OCCR group (P = 0.0197). On the other hand, BRCA2 variants did not exhibit any particular trend (32.8 months vs. 27.9 months, P = 0.468). However, no significant differences were detected in OS between patients with BRCA1/2 PVs, regardless of the location of the variants. CONCLUSIONS: Patients with BRCA1 PV in the OCCR had shorter PFS than those outside the OCCR. This tendency was more pronounced in the platinum-sensitive subgroup. To our knowledge, this is the first study of BRCA1/2 mutations based on the OCCR.

Is Korean society prepared for the financial burden of novel anticancer drugs? A survey of willingness to pay among National Health Insurance beneficiaries.

PURPOSE: Since South Korea's 5-year policy of increasing National Health Insurance (NHI) coverage began in 2017, related pharmaceutical expenditures have increased by 41%. Thus, there is a critical need to examine society's willingness to pay (WTP) for increased premiums to include new anticancer drugs in NHI coverage. METHODS: Participants aged 20-65 were invited to a web-based online survey. The acceptable effectiveness threshold for a new anticancer drug to be included in NHI coverage and the WTP for an anticancer drug with modest effectiveness were determined by open-ended questions. RESULTS: A total of 1817 respondents completed the survey. Participants with a family history of cancer or a higher perceived risk of getting cancer had significantly higher WTPs (RR [relative risk] = 1.17 and 1.21, both P = 0.012). Participants who agreed on adding coverage for new anticancer drugs with a life gain of 3 months had a higher WTP (RR = 1.70, P < 0.0001). These associations were greater among the employed and low-income groups. The adjusted mean of acceptable effectiveness for a new anticancer drug was 21.5 months (interquartile range [IQR] = 19.3 to 24.0, median = 21.9). The WTP for a new anticancer drug with a life gain of 3 months was $5.2 (IQR = 4.0 to 6.0, median = 4.6). CONCLUSION: The unrealistic expectations in Korean society for new anticancer agents may provoke challenging issues of fairness and equity. Although Korean society is willing to accept premium increases, our data suggest that such increases would benefit only a small proportion of advanced cancer patients.

How to manage synchronous endometrial and ovarian cancer patients?

BACKGROUNDS: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC). METHODS: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses. RESULTS: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis. CONCLUSIONS: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.

The Knowledge and Attitude of Patients Diagnosed with Epithelial Ovarian Cancer towards Genetic Testing.

This study assessed the knowledge and attitude of patients with ovarian cancer (OC) toward OC and next generation sequencing (NGS). The data, including characteristics of patients, their knowledge about OC and their knowledge and attitude of NGS, were collected from June to October 2018. Of the 103 participants, 70.9% (n = 73) had cancer within the second-degree relatives, and 18.4% (n = 19) had BRCA pathogenic mutations. The percentage of right answer for the knowledge about OC and NGS was 64.7% (11/17) and 50% (6/12), respectively. The median number of patients who had positive expectations for the genetic test was 34 (range, 22-44). Based on a first-degree familial history, patients had a different degree of knowledge about OC (11 vs. 8.5, p = 0.026) and NGS (6.5 vs. 5, p = 0.011), but patients with a BRCA pathogenic mutation did not have a different degree of knowledge about OC and NGS panel testing. High-income families had a more positive attitude towards the genetic test than low-income families (p = 0.005). Women with OC do not have enough knowledge about OC (11/17, 64.7%) and NGS (6/12, 50%) but they showed a positive attitude toward the NGS test. These women need OC and NGS educational intervention.

Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation.

PURPOSE: The BRCA1 or BRCA2 gene is transmitted in an autosomal dominant fashion, and genetic testing of first-degree relatives of patients with family-specific mutation (FSM) is recommended. This study examined factors affecting the uptake of FSM testing among relatives of patients with peritoneal, ovarian, or fallopian tube (POFT) cancer with confirmed BRCA1 or BRCA2 germline mutation. MATERIALS AND METHODS: Data from medical charts of 392 eligible patients and their relatives who had undergone outpatient genetic counseling/testing were retrospectively reviewed. Clinical factors were compared between family members who had and had not undergone genetic counseling/testing. RESULTS: The uptake of FSM testing was 30.5% (129/423) among first-degree living relatives and 53.5% (69/129) within the overall family unit. The average time from genetic testing of the proband to the first FSM test within a family was 168 days (range, 23 to 681 days). Having a living father (33.8% vs. 13.3%, p=0.007) and daughter (79.4% vs. 60.3%, p=0.019) increased the uptake of FSM testing. FSM testing was more likely among female than among male relatives of cancer patients (40.9% vs. 17.6%, p < 0.001). CONCLUSION: Approximately one-third of first-degree relatives of patients with a POFT cancer with BRCA1 or BRCA2 mutation underwent FSM testing. Having a living father or daughter was a factor affecting the uptake of FSM testing, which was higher among female than among male relatives of the proband. This discrepancy might be due to a misconception that the BRCA gene is associated with women rather than with men.

Prevalence of pathogenic variants in actionable genes in advanced ovarian cancer: a next-generation sequencing analysis of a nationwide registry study.

BACKGROUND: We examined the actionable genomic alterations in ovarian cancer by analysing the nationwide registry of next-generation sequencing (NGS) data. METHODS: From March 2017 to December 2018, 16,458 patients with cancer underwent NGS testing under the interim coverage programme for NGS provided by the National Health Insurance of Korea. Among these patients, 779 patients had advanced ovarian cancer. Fifty-eight mutations were reported as pathogenic variants, which included likely pathogenic variants, and 55 theoretically actionable genes were analysed. RESULTS: The prevalence of pathogenic mutations in the population was 81.5%, whereas 11.6% of the population had neither a pathogenic mutation nor a variant of unknown significance. Common pathogenic mutations shared by at least 3% of the study population were mutations in TP53 (61.5%), BRCA1 (12.2%), PIK3CA (10.4%), KRAS (10.3%), BRCA2 (9.6%) and PTEN (3.7%). BRCA1/2 pathogenic mutations were found in 14.0% (42 of 300, 95% confidence interval = 10-18%) of the patients with TP53 wild-type tumours, comprising approximately one-quarter (25.9%) of the total observed BRCA1/2 pathogen mutations. At least one pathogenic mutation in a theoretically actionable gene was found in 49.2% of patients. Among patients without a BRCA1/2 pathogenic mutation, mutations were frequently observed in KRAS (12.2%), PIK3CA (10.4%) and PTEN (4.2%). PTCH1 mutations were correlated with ATM, NF1, ERBB2 and MTOR mutations (adjusted p = 0.0054, p = 0.0035, p = 0.0010 and p = 0.0003, respectively). CONCLUSIONS: Almost half of patients with ovarian cancer could be estimated as theoretical candidates for genomic medicine. Substantial BRCA1/2 pathogenic mutations were observed in patients not harbouring a TP53 mutation.

Glycolytic phenotypes in an evaluation of ovarian carcinoma based on carcinogenesis and BRCA mutation.

BACKGROUNDS: Recently, a dualistic carcinogenesis model of ovarian cancer has emerged. We aimed to investigate differences in the glycolytic phenotypes of type I and type II ovarian carcinoma on the basis of FDG uptake and in the pathological features according to tumour grade and histology. MATERIALS AND METHODS: In total, 386 epithelial ovarian carcinoma patients underwent debulking surgery, and the histopathological results of the patients were retrospectively reviewed from 2003 to 2017. Among these patients, 170 patients had histopathological data that were available due to primary cytoreductive surgery and could be analysed regarding FDG avidity in type I and type II ovarian cancer. The FDG uptake of the tumour (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were analysed according to the tumour grade, histology and type of ovarian carcinogenesis (type I and II) and prognosis. RESULTS: Among the 386 patients, there was a significant difference in SUVmax among ovarian cancer subtypes. There was a significant increase in SUVmax as the tumour grade increased (8.08 ±â€¯0.63, 10.5 ±â€¯0.40, and 12.7 ±â€¯0.38 for grades I, II and III, respectively, Kruskal-Wallis test, p < 0.0001). Among the 90 type I and 80 type II ovarian carcinoma patients, there was a significant difference in SUVmax (type I and II, 9.47 ±â€¯0.54 and 12.97 ±â€¯0.70, respectively, Mann-Whitney test, p = 0.0003). However, no significant change in SUVmax was observed between BRCA-positive and BRCA-negative patients (N = 80, 13.8 ±â€¯5.78 and 12.4 ±â€¯6.30, Student's t-test, p = 0.3075). Among clinicopathologic and metabolic parameters, type of ovarian cancer, MTV and CA125 were significant factors in the prediction of recurrence. CONCLUSIONS: The glycolytic phenotype was related to tumour grade and histological subtype, with significant differences between type I and II ovarian cancer. SUVmax of the ovarian cancer would be considered in the differentiation of type I and II ovarian cancer.

Survival Effects of Cytoreductive Surgery for Refractory Patients after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

PURPOSE: Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. RESULTS: Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; p=0.011). High-grade serous histology was associated with longer OS than non-high-grade serous types. In group A, optimal surgery resection (<1 cm) was achieved after CRS in 6 patients (46%). Multivariate analysis showed that the treatment option was the only independent predictive factor for OS (hazard ratio, 2.30; 95% confidence interval, 1.02-5.17; p=0.044). CONCLUSION: CRS may result in a survival benefit even in patients with AEOC who develop PD after NAC.

The survival effect of ovary preservation in early stage endometrial cancer: a single institution retrospective analysis.

PURPOSE: We investigated the effect of ovary preserving surgery in early International Federation of Obstetrics and Gynecology (FIGO) stage endometrial cancer patients. METHODS: Medical records were retrospectively reviewed for 539 patients who were diagnosed with early stage endometrial cancer between Jan 2006 and Dec 2017. Patients were categorized into ovary preservation and ovary removal groups. Demographics, recurrence free survival (RFS), and five-year overall survival (OS) rate were compared, and the clinical factors affecting survival were evaluated by univariate and multivariate analysis. RESULTS: The median follow-up period was 85 months (range, 6-142 months), and the median age was 52.7 years. The mean age was higher in the ovary removal group than in the ovary preservation group (54.4 vs 40.94 years; P < 0.001). The ovary preservation group showed an earlier FIGO stage than the ovary removal group (P = 0.0264). There was a greater incidence of adjuvant chemotherapy administration in the removal group. There were no statistical differences in other baseline characteristics. When comparing the RFS and OS rates, there were no statistical differences between the preservation and removal groups. (recurrence free rate 98.5% vs 92.7%, p = 0.4360, and 5-year survival rate 98.6% vs 93.0%, p = 0.0892, respectively). Endometrioid histology (p = 0.006) and post-operative adjuvant chemotherapy (p = 0.0062) were related to OS, and adjuvant chemotherapy (p < 0.001) and radiotherapy (p = 0.005) were related to RFS. CONCLUSIONS: Ovary preservation in early stage endometrial cancer is worth considering, as it does not affect survival in early stage endometrial cancer patients.