Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation / Journal of the Korean Cancer Association, 대한암학회지

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.

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.

Comparing prediction models for lymph node metastasis risk in endometrial cancer: the winner may not take it all / 부인종양

No abstract available.

Survival outcomes after extensive cytoreductive surgery and selective neoadjuvant chemotherapy according to institutional criteria in bulky stage IIIC and IV epithelial ovarian cancer / 부인종양

OBJECTIVE: To investigate the survival outcomes in patients with bulky stage IIIC and IV ovarian cancer, treated by primary debulking surgery (PDS) and selective use of neoadjuvant chemotherapy (NAC) according to institutional criteria. METHODS: Medical records for advanced ovarian cancer patients who were treated at National Cancer Center (NCC) between December 2000 and March 2009 were retrospectively reviewed in the comprehensive cancer center. Bulky stage IIIC and IV ovarian cancer cases were included. Current NCC indication for NAC is determined based on patients' performance status and/or computerized tomography (CT) findings indicating difficult cytoreduction. After NAC, all traces of regressed metastatic ovarian cancer, potentially including chemotherapy-resistant cancer cells, were surgically removed. RESULTS: Of the 279 patients with bulky stage IIIC and IV, 143 (51%) underwent PDS and 136 (49%) received NAC. No gross residual and residual tumor measuring ≤1 cm was achieved in 66% and 96% of the PDS group and 79% and 96% of the NAC group, respectively. The median progression-free survival (PFS) and overall survival (OS) time were 20 months and not reached, but might be estimated more than 70 months in the PDS group and 15 and 70 months in the NAC group, respectively. CONCLUSION: Extensive cytoreductive surgery to minimize residual tumor and selective use of NAC based on the institutional criteria could result in improved survival outcomes. Until further studies can be done to define the selection criteria for NAC after surgery, institutional criteria for NAC should consider the ability of the surgeon and institutional capacity.

Do we need a better marker for successful ovarian cancer surgery? / 부인종양

No abstract available.

The Effect of Breastfeeding Duration and Parity on the Risk of Epithelial Ovarian Cancer: A Systematic Review and Meta-analysis / 예방의학회지

OBJECTIVES: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). METHODS: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p=0.17; Q=18.79, I²=25.5%). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. CONCLUSIONS: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.

Second Primary Cancer after Diagnosis and Treatment of Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to investigate the incidence and survival outcomes of second primary cancers after the diagnosis of cervical cancer. MATERIALS AND METHODS: Data from the Korea Central Cancer Registry between 1993 and 2010 were reviewed and analyzed. Standardized incidence ratios (SIRs) of second primary cancers among women with cervical cancer were analyzed. Kaplan-Meier survival curves were constructed for cervical cancer patients with or without a second primary cancer. RESULTS: Among 72,805 women with cervical cancer, 2,678 (3.68%) developed a second primary cancer within a mean follow-up period of 7.34 years. The overall SIR for a second cancer was 1.08 (95% confidence interval, 1.04 to 1.12). The most frequent sites of second primary cancers were the vagina, bone and joints, vulva, anus, bladder, lung and bronchus, corpus uteri, and esophagus. However, the incidence rates of four second primary cancers (breast, rectum, liver, and brain) were decreased. The 5-year and 10-year overall survival rates were 78.3% and 72.7% in all women with cervical cancer, and for women with a second primary cancer, these rates were 83.2% and 65.5% from the onset of cervical cancer and 54.9% and 46.7% from the onset of the second primary cancer, respectively. CONCLUSION: The incidence rates of second primary cancers were increased in women with cervical cancer compared to the general population, with the exception of four decreasing cancers. The 10-year overall survival rates were decreased in cervical cancer patients with a second primary cancer.

Incidence of epithelial ovarian cancer according to histologic subtypes in Korea, 1999 to 2012 / 부인종양

OBJECTIVE: To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012. METHODS: Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (59 years), and age-specific incidence rates were compared. RESULTS: Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, -1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999. CONCLUSION: The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.

Major clinical research advances in gynecologic cancer in 2014 / 부인종양

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

Controversies in the management of endometrial cancer: a survey of the Korean Gynecologic Oncology Group / 부인종양

OBJECTIVE: To identify current practice patterns for unresolved issues in the surgical and adjuvant management of endometrial cancer in Korea. METHODS: We designed and conducted a survey of all 218 active members of the Korean Gynecologic Oncology Group to try to identify how they would manage various case scenarios for endometrial cancer. Data were collected using an Internet survey database. RESULTS: A total of 108 members (49.5%) responded to the survey. Laparoscopy (81.6%) was the most commonly used mode of surgery in early-stage endometrial cancer. Of all the respondents, 19.8% stated that lymphadenectomy could be omitted and 21.7% recommended selective lymphadenectomy based on sentinel biopsy or frozen results for patients with presumed stage IA/grade 1 disease. On the other hand, 71.9% of respondents recommended para-aortic lymphadenectomy for patients with presumed stage IB/grade 1 disease and 86.4% recommended this treatment for presumed stage IB/grade 3 disease. The majority of respondents performed adjuvant therapy for stage IB/grade 2 (91.7%), IB/grade 3 (99.0%), and stage II (89.6%). Whole pelvic radiotherapy and vaginal brachytherapy were the most frequently used options among these patients. All respondents administered adjuvant therapy when node metastasis was found, and concurrent chemoradiotherapy (53.2%) was the most preferred option for stage IIIC1 disease. CONCLUSION: There is broad variation in both the surgical and adjuvant treatment of endometrial cancer among Korean gynecologic oncologists.

Completeness of pedigree and family cancer history for ovarian cancer patients / 부인종양

OBJECTIVE: To investigate the completeness of pedigree and of number of pedigree analysis to know the acceptable familial history in Korean women with ovarian cancer. METHODS: Interview was conducted in 50 ovarian cancer patients for obtaining familial history three times over the 6 weeks. The completeness of pedigree is estimated in terms of familial history of disease (cancer), health status (health living, disease and death), and onset age of disease and death. RESULTS: The completion of pedigree was 79.3, 85.1, and 85.6% at the 1st, 2nd, and 3rd time of interview and the time for pedigree analysis was 34.3, 10.8, and 3.1 minutes, respectively. The factors limiting pedigree analysis were as follows: out of contact with their relatives (38%), no living ancestors who know the family history (34%), dispersed family member because of the Korean War (16%), unknown cause of death (12%), reluctance to ask medical history of relatives (10%), and concealing their ovarian cancer (10%). The percentage of cancers revealed in 1st (2%) and 2nd degree (8%) relatives were increasing through surveys, especially colorectal cancer related with Lynch syndrome (4%). CONCLUSION: Analysis of pedigree at least two times is acceptable in Korean woman with ovarian cancer from the first study. The completion of pedigree is increasing, while time to take family history is decreasing during three time survey.

Major clinical research advances in gynecologic cancer in 2013 / 부인종양

In 2013, 10 topics were selected for major clinical research advances in gynecologic oncology; these included three topics regarding cervical cancer, three regarding ovarian cancer, two regarding endometrial cancer, and one each regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab was first demonstrated to exhibit outstanding clinical efficacy in a recurrent, metastatic setting. Regarding cervical cancer screening, visual inspections with acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow-up results of four randomized controlled trials of human papillomavirus-based screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before chemoradiation for locally advanced cervical cancer was the final topic for cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted agents administered according to combination or maintenance schedules were discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and farletuzumab were discussed for platinum-sensitive disease. The final overall survival data associated with a combination of bevacizumab and chemotherapy for platinum-resistant disease were briefly summarized. For endometrial cancer, the potential clinical efficacy of metformin, an antidiabetic drug, in obese patients was followed by integrated genomic analyses from the Cancer Genome Atlas Research Network. For breast cancer, three remarkable advances were reviewed: the long-term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2-positive disease, and the approval of pertuzumab in a neoadjuvant setting with a pathologic complete response as the surrogate endpoint. Finally, the recent large studies of intensity-modulated radiotherapy for gynecologic cancer were briefly summarized.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Coexisting carcinoma in endometrial hyperplasia: does more risk factor mean better discrimination? / 부인종양

No abstract available.

Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010 / 부인종양

OBJECTIVE: To investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females. METHODS: Data from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated. RESULTS: The absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females or =80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%). CONCLUSION: ASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.

Pelvic exenteration for recurrent cervical cancer: ten-year experience at National Cancer Center in Korea / 부인종양

OBJECTIVE: To evaluate survival and morbidity after pelvic exenteration (PE) for the curative management of recurrent cervical cancer. METHODS: We retrospectively evaluated patients with recurrent cervical cancer who underwent PE from January 2001 to April 2011. Patients were identified from the registry of our institution. The clinical status and demographic information was obtained by reviewing the medical records. RESULTS: Sixty-one recurrent cervical cancer patients underwent PE. Patients who received radiotherapy, operation, chemotherapy before PE were 98%, 41%, and 23%, respectively. The total morbidity rate was 44%; 10 (16%) patients had early complications (30 days or less after PE), whereas 22 (36%) patients had late complications. Wound problems were common early complications (7/18), and bowel fistulas were common late complications (9/30). The five-year overall survival and five-year disease-free survival were 56% and 49%, respectively. Median follow-up was 22 months (range, 1.8 to 60 months). Affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement. CONCLUSION: Our overall 5-year survival is encouraging. Although the morbidity rate is still high, PE is a potentially curative opportunity in gynecological malignancies with no other treatment options. The most important factors for overall survival after PE are the resection margin status, pelvic wall involvement and rectal involvement.

How low is low enough? Evaluation of various risk-assessment models for lymph node metastasis in endometrial cancer: a Korean multicenter study / 부인종양

OBJECTIVE: The aim of this study was to identify a standard for the evaluation of future models for prediction of lymph node metastasis in endometrial cancer through estimation of performance of well-known surgicopathological models. METHODS: Using the medical records of 947 patients with endometrial cancer who underwent surgical management with lymphadenectomy, we retrospectively assessed the predictive performances of nodal metastasis of currently available models. RESULTS: We evaluated three models included: 1) a model modified from the Gynecologic Oncology Group (GOG) pilot study; 2) one from the GOG-33 data; and 3) one from Mayo Clinic data. The three models showed similar negative predictive values ranging from 97.1% to 97.4%. Using Bayes' theorem, this can be translated into 2% of negative post-test probability when 10% of prevalence of lymph node metastasis was assumed. In addition, although the negative predictive value was similar among these models, the proportion that was classified as low-risk was significantly different between the studies (56.4%, 44.8%, and 30.5%, respectively; p<0.001). CONCLUSION: The current study suggests that a false negativity of 2% or less should be a goal for determining clinical usefulness of preoperative or intraoperative prediction models for low-risk of nodal metastasis.

Pelvic exenteration for recurrent cervical cancer: ten-year experience at National Cancer Center in Korea / 부인종양

OBJECTIVE: To evaluate survival and morbidity after pelvic exenteration (PE) for the curative management of recurrent cervical cancer. METHODS: We retrospectively evaluated patients with recurrent cervical cancer who underwent PE from January 2001 to April 2011. Patients were identified from the registry of our institution. The clinical status and demographic information was obtained by reviewing the medical records. RESULTS: Sixty-one recurrent cervical cancer patients underwent PE. Patients who received radiotherapy, operation, chemotherapy before PE were 98%, 41%, and 23%, respectively. The total morbidity rate was 44%; 10 (16%) patients had early complications (30 days or less after PE), whereas 22 (36%) patients had late complications. Wound problems were common early complications (7/18), and bowel fistulas were common late complications (9/30). The five-year overall survival and five-year disease-free survival were 56% and 49%, respectively. Median follow-up was 22 months (range, 1.8 to 60 months). Affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement. CONCLUSION: Our overall 5-year survival is encouraging. Although the morbidity rate is still high, PE is a potentially curative opportunity in gynecological malignancies with no other treatment options. The most important factors for overall survival after PE are the resection margin status, pelvic wall involvement and rectal involvement.

How low is low enough? Evaluation of various risk-assessment models for lymph node metastasis in endometrial cancer: a Korean multicenter study / 부인종양

OBJECTIVE: The aim of this study was to identify a standard for the evaluation of future models for prediction of lymph node metastasis in endometrial cancer through estimation of performance of well-known surgicopathological models. METHODS: Using the medical records of 947 patients with endometrial cancer who underwent surgical management with lymphadenectomy, we retrospectively assessed the predictive performances of nodal metastasis of currently available models. RESULTS: We evaluated three models included: 1) a model modified from the Gynecologic Oncology Group (GOG) pilot study; 2) one from the GOG-33 data; and 3) one from Mayo Clinic data. The three models showed similar negative predictive values ranging from 97.1% to 97.4%. Using Bayes' theorem, this can be translated into 2% of negative post-test probability when 10% of prevalence of lymph node metastasis was assumed. In addition, although the negative predictive value was similar among these models, the proportion that was classified as low-risk was significantly different between the studies (56.4%, 44.8%, and 30.5%, respectively; p<0.001). CONCLUSION: The current study suggests that a false negativity of 2% or less should be a goal for determining clinical usefulness of preoperative or intraoperative prediction models for low-risk of nodal metastasis.

Prediction of a high-risk group based on postoperative nadir CA-125 levels in patients with advanced epithelial ovarian cancer / 부인종양

OBJECTIVE: We aimed to determine the ideal cut-off of nadir serum CA-125 level for prediction of progression free survival. METHODS: Among 267 patients who achieved complete remission after chemotherapy, the correlation between nadir CA-125 and progression free survival were compared among the subgroups classified according to the distribution of CA-125. The diagnostic odds ratio and area under the receiver operator characteristics curve were compared at various cut-off points. RESULTS: The nadir CA-125 levels did not have prognostic value under 12 U/mL (to 75 percentile). In contrast, they were significantly correlated with progression free survival only when the CA-125 level was greater than 12, which was 75 percentile (p=0.034). In predicting progression free survival 18 U/mL showed a hazard ratio of 2.85 (95% confidence interval, 1.70 to 4.76; p<0.001); patients with nadir levels between 18 and 12 U/mL showed a the hazard ratio of 1.68 (95% confidence interval, 1.11 to 2.56; p=0.015) compared with those whose nadir levels were under 12 U/mL. CONCLUSION: The predictive power of the traditional cut-off of 10 U/mL to classify a risk group or to identify high risk patients was unsatisfactory. The optimal diagnostic performance was observed at the cut-off of 18 U/mL and this can be proposed to dichotomize cut-off values to predict outcomes among individual patients.