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Background As next‐generation sequencing (NGS) technology matures, various amplicon‐based NGS tests for BRCA1/2 genotyping have been introduced. This study was designed to evaluate an NGS test using a newly released amplicon‐based panel, AmpliSeq for Illumina BRCA Panel (AmpliSeq panel), for detection of clinically significant BRCA variants, and to compare it to another amplicon‐based NGS test confirmed by Sanger sequencing. Methods We reviewed BRCA test results done by NGS using the TruSeq Custom Amplicon kit from patients suspected of hereditary breast/ovarian cancer syndrome (HBOC) in 2018. Of those, 96 residual samples with 100 clinically significant variants were included in this study using predefined criteria: 100 variants were distributed throughout the BRCA1 and BRCA2 genes. All target variants were confirmed by Sanger sequencing. Duplicate NGS testing of these samples was performed using the AmpliSeq panel, and the concordance of results from the two amplicon‐based NGS tests was assessed. Results Ninety‐nine of 100 variants were detected in duplicate BRCA1/2 genotyping using the AmpliSeq panel (sensitivity, 99%; specificity, 100%). In the discordant case, one variant (BRCA1 c.3627dupA) was found only in repeat 1, but not in repeat 2. Automated nomenclature of all variants, except for two indel variants, was in consensus with Human Genome Variation Society nomenclature. Conclusion Our findings confirm that the analytic performance of the AmpliSeq panel is satisfactory, with high sensitivity and specificity., One hundred target variants were distributed throughout the BRCA1 and BRCA2 genes. AmpliSeq for Illumina BRCA Panel was satisfactory with 99% sensitivity and 100% specificity. Visual confirmation was needed for adequate reporting of indel variants.

We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients.We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed.Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001).Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Although next-generation sequencing (NGS) is widely used for

Background Distant metastasis occasionally occurs in patients who have been diagnosed with colorectal cancer (CRC), but it occurs in a few patients with stage I CRC. The vagina as a metastasis site has also been reported, albeit rarely. Most reported cases of vaginal metastasis (VM) report their origin from advanced CRC. We encountered a patient who was diagnosed with isolated VM originating from stage I colon cancer (T2N0) and herein present the case of this patient. Case summary A 63-year-old woman visited the outpatient clinic because of a positive result from a stool occult blood test. She underwent laparoscopic anterior resection and was pathologically diagnosed with stage I (T2N0) sigmoid colon cancer. Neither lymphovascular invasion nor perineural invasion was observed. Ten months following the surgery, isolated vaginal metastases were detected on gynecologic examination. The examination was performed due to vaginal spotting. A transvaginal wide excision was performed, and no other adjuvant treatment was provided after discussion with a multidisciplinary team and the patient. Subsequently, a new VM was discovered after 33 mo. An additional transvaginal excision was performed. To date, there has been no evidence of further disease progression. From the time of diagnosis of VM, the patient's overall survival has been 54 mo. Conclusion VM can occur as a result of early-stage colorectal cancer. Surgeons should consider the possibility of VM following complaints of gynecologic symptoms following surgery.

Objective Circulating cell-free tumor DNA (cfDNA) is the DNA released by apoptotic and necrotic cells of the primary tumor into the blood during the period of tumor development. The cfDNA reflects the genetic and epigenetic alterations of the original tumor. TP53 mutations are a defining feature of high-grade serous ovarian carcinoma. We optimized the methods for detecting TP53 mutations in cfDNA from blood samples. We confirmed the correlation of TP53 mutation in primary ovarian cancer tissue and it in cfDNA using digital polymerase chain reaction (dPCR). Methods We found 12 frequent mutation sites in TP53 using The Cancer Genome Atlas and Catalogue of Somatic Mutations in Cancer data and manufactured 12 primers. The mutations in tissues were evaluated in fresh-frozen tissue (FFT) and formalin-fixed paraffin-embedded tissue (FFPET). We performed a prospective analysis of serial plasma samples collected from 4 patients before debulking surgery. We extracted cfDNA and calculated its concentration in blood. dPCR was used to analyze TP53 mutations in cfDNA, and we compared TP53 mutations in ovarian cancer tissue with those in cfDNA. Results Ten primers out of 12 detected the presence of TP53 mutations in FFT, FFPET, and cfDNA. In FFT and FFPET tissue, there were no significant differences. The average cfDNA concentration was 2.12±0.59 ng/mL. We also confirmed that mutations of cfDNA and those of FFT were all in R282W site. Conclusion This study developed detection methods for TP53 mutations in cfDNA in ovarian cancer patients using dPCR. The results demonstrated that there are the same TP53 mutations in both ovarian cancer tissue and cfDNA.

Purpose Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment. Materials and methods In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR). Results Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m2 Genexol-PM or 174.24±3.81 mg/m2 Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable. Conclusion Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

Objective To identify risk factors for distant recurrence in node-positive cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection (PLND) with para-aortic lymph node sampling (PALNS) or para-aortic lymph node dissection (PALND). Methods A total of 299 patients in whom lymph node metastasis was confirmed after radical surgery at Asan Medical Center for stage IA2 to IIB cervical cancer from February 2001 to December 2012 were identified. In all, 72 (24.1%) patients underwent PLND only and 227 (75.9%) underwent PLND with PALNS or PALND. Four patients were excluded due to diagnosed with small cell carcinoma. The clinicopathologic data of 223 patients were retrospectively analyzed. Distant recurrence was defined as recurrence at a site over the pelvic radiation field. Results Among all 223 study patients, the mean number of positive lymph nodes was 4.46. There were 54 (24.2%) patients with distant metastasis. Multivariate analyses using the Cox proportional hazards model showed that histologic types (HR=3.031, P ≤0.001 for adenocarcinoma, HR=2.302, P =0.066 for adenosquamous carcinoma), number of positive lymph nodes (HR=1.077, P ≤0.001), and surgical stage (HR=1.264, P =0.022) were independent risk factors for distant recurrence of cervical cancer. A scoring system for the prediction of distant recurrence was generated by incorporating these factors and showed good discrimination and calibration (concordance index of 0.753). In an internal validation set, this scoring system showed good discrimination with a C-statistics of 0.777. According to the Hosmer-Lemeshow test, the chi-square was 0.650 and the P -value was 0.723. Conclusions We have developed a robust scoring system that can predict the risk of distant recurrence in node-positive cervical cancer patients after radical operation. This scoring system was used to identify a group of patients who required systemic control of distant micrometastasis. This group of patients is an appropriate target for consolidation chemotherapy after concurrent chemoradiation therapy.

Objective The study aims to identify preoperative predictors of complete cytoreduction and early recurrence and death in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy (NACT). Methods We performed a retrospective analysis of 85 patients who underwent 3 cycles of NACT. Patients were divided into 2 groups according to residual tumor at interval debulking surgery (IDS), and clinicopathologic, surgical, and follow-up data were compared. Results Cancer antigen 125 (CA-125) levels before the IDS after completion of NACT were higher in the residual tumor group (42.0 vs 116.6 U/mL, P = 0.006). The drop rate of CA-125 after NACT was higher in the no residual tumor group (96.8% vs 89.9%, P = 0.001). Patients with residual tumor showed lower disease-free and overall survival outcomes than patients with no residual tumor. In univariate analysis, CA-125 of 100 U/mL or less before IDS and a drop rate after NACT greater than 80% were preoperative predictive factors for complete cytoreduction. In multivariate analysis, a drop rate of CA-125 after NACT greater than 80% was an independent preoperative predictive factor for complete cytoreduction (P = 0.002). Progressive disease on follow-up image during NACT was an independent preoperative predictive factor for early recurrence and death (P Conclusions A significant drop of CA-125 after NACT and progressive disease on follow-up image are independent preoperative predictors for complete cytoreduction and early recurrence and death.

The RB1/E2F1 signaling pathway is frequently deregulated in colorectal cancer and has been suggested to intersect with Wnt/β-catenin and PI3K/Akt pathways, but molecular evidence for this link is lacking. In this study, we demonstrate that phospholipase D1 (PLD1), a transcriptional target of β-catenin/TCF4, orchestrates functional interactions between these pathways during intestinal tumor development. Overexpression of PLD1 in intestinal epithelial cells protected cells from apoptosis induced by PLD1 ablation in the Apcmin/+ mouse model of intestinal tumorigenesis. Mechanistic investigations revealed that genetic and pharmacologic targeting of PLD1 promote the E2F1-dependent apoptotic program via both miR-192/4465–mediated downregulation of RB1 and inhibition of Akt–TopBP1 pathways. Moreover, the miRNA–RB1 axis and Akt pathway also contributed to the PLD1-mediated self-renewal capacity of colon cancer–initiating cells. Finally, PLD1-driven E2F1 target gene expression positively correlated with tumor stage in patients with colorectal cancer. Overall, our findings suggest that PLD1 mediates cross-talk between multiple major signaling pathways to promote the survival and malignancy of colon cancer cells and may therefore represent an ideal signaling node for therapeutic targeting. Cancer Res; 77(1); 142–52. ©2016 AACR.

The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.

This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples with OC (mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772&ndash, 0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714&ndash, 0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

In 2016, 9-valent human papillomavirus (HPV) vaccine has been newly introduced in Korea, thus the need to develop recommendations for the vaccine has raised. Until we decide to develop a guideline, no further studies on the bi-valent or quadri-valent HPV vaccine have been announced. We searched and reviewed the literatures focused on the efficacy of 9-valent HPV vaccine, the ideal age of 3-dose schedule vaccination, the efficacy of 9-valent HPV vaccine in middle-aged women, the efficacy of the 2-dose schedule vaccination, the safety of 9-valent HPV vaccine, the possibility of additional 9-valent HPV vaccination, and cross-vaccination of 9-valent HPV vaccine. So, Korean Society of Gynecologic Oncology (KSGO) developed a guideline only for 9-valent HPV vaccine.

Robot-assisted laparoscopic myomectomy (RALM) has broadened the indications even in com-plex myomas. However, the high cost of RALM remains the main disadvantage. Therefore, a surgical technique that can reduce the cost of RALM and still has the advantages of robotic sur-gery is required. We propose a “locking suture on myoma (LSOM)” technique and compared the operative and perioperative outcomes of patients who underwent RALM with or without the LSOM technique. We included 337 patients who underwent RALM with (n = 160) or without (n = 177) the LSOM technique between March 2019 and August 2020. The LSOM group had low parity and gravidity, with a low rate of Cesarean sections. Myoma type was not different between the groups, however, patients in the LSOM group had larger, heavier, and higher number of myo-mas, although fewer patients had multiple myomas and were discharged earlier. Total operating time, estimated blood loss, pre- and postoperative hemoglobin levels, transfusion rate, and postoperative fever were not different between the two groups. In conclusion, the LSOM tech-nique may be a viable surgical option for myomas, as it can reduce the cost of RALM by obviat-ing the need for robotic Tenaculum forceps.

Contrasting human security with national security, this chapter examines South Korea’s policies toward global refugees and North Korean defectors, an effective indicator of regime instability. It is argued that the security and welfare of individual persons, which are the very reason for the existence of a sovereign state, must be prioritized in human security practice. Policy development in this regard is essential for a middle-power nation. Some policy considerations are provided for the examination of refugee responses from the human security perspective, particularly regarding how to make stakeholder support more comprehensive and how to promote bottom-up engagement and empowerment.

Background Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. Method We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. Results A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006–2010 and 6.06 for those who died during 2011–2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006–2010) vs. 4.93 times (2011–2015; p

To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy (LH).Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups. Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach. Secondary outcomes were postoperative pain and operative scar.Demographic parameters including age, body mass index, parity, and history of vaginal and cesarean delivery were comparable between the 2 groups. The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8% and 10.3%, respectively. Conversions were similar between the groups with 4% of single-port cases and .8% of multiport cases. Transfusions were the most frequent complication required in 4.0% of single-port cases and 7.9% of multiport cases, with no difference between the groups. Concerning secondary outcomes, postoperative pain score and patient and observer scar assessment were not different between the 2 groups. Although not a specific outcome measure, there was no difference between the groups in blood loss, operative time, and postoperative hospital stay.Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates, including transfusion. However, the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes. These findings were demonstrated by multi-institutional surgeons in Korea.

Objective Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. Materials and methods We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. Results The median age was 55.5 years (range, 37–68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5–25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8–173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9–18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. Conclusion Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

ObjectiveThe purpose of this study was to identify preoperative clinicopathological predictive factors for lymph node (LN) metastasis in women diagnosed with uterine papillary serous carcinoma (UPSC).MethodsWomen diagnosed with UPSC in our institution from 1997 to 2012 were identified. All patients underwent hysterectomy and bilateral salpingo-oophorectomy plus pelvic and/or para-aortic lymphadenectomy. The predictive values of the risk factors for LN metastasis were analyzed using χ2 and multivariate logistic regression analyses.ResultsA total of 94 patients met our study criteria. A CA-125 cutoff of 47.5 IU/mL on the receiver operating characteristic curve provided the best sensitivity and specificity (56.5% vs 90.1%, respectively) for LN metastasis prediction. The sensitivities and specificities of old age (≥60 years), body mass index of 25 kg/m2 or greater, deep myometrial invasion, tumor size greater than 2 cm, tumor size greater than 4 cm, preoperative CA-125 greater than 47.5 IU/mL, LN metastasis on imaging, and extrauterine spread on imaging for the presence of a positive LN were 39.1%, 34.8%, 30.4%, 34.8%, 21.7%, 56.5%, 43.5%, and 52.2%, and 52.1%, 45.1%, 78.9%, 57.7%, 83.1%, 90.1%, 93.0%, and 90.1%, respectively. Preoperative CA-125 (P < 0.001), LN metastasis on preoperative imaging (P < 0.001), and extrauterine spread on preoperative imaging (P = 0.009) were risk factors for LN metastasis on univariate analysis. Multivariate analysis revealed that preoperative CA-125 (P = 0.001) was the only independent risk factor for LN metastasis.ConclusionsPreoperative CA-125 is a preoperative predictive factor for LN metastasis in UPSC.

Objective This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. Methods This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m2) between 1st December 2014 and 31th July 2016. Results The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Objective This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. Methods This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. Results In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. Conclusion Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncologic Group (KGOG) has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we focused on radical hysterectomy and lymphadenectomy, and we developed a KGOG classification for those conditions.

Objective Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age. This study aimed to find the incidence of precursor lesions and cancer after RRSO. Methods We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2010 to 2014. From 2013, all cases were examined according to the Sectioning and Extensively Examining the Fimbria (SEE/FIM) protocol and underwent immunohistochemically staining. RRSO was performed in 63 patients, 27 in 2010 to 2012 and 36 in 2013 to 2014. Results The median age at RRSO was 46.5 years (range, 32 to 73 years). Occult invasive cancer was detected in eight patients, of ovarian origin in five and of tubal origin in three. All occult invasive cancer cases with metastasis were detected in patients older than 40 years. Of the 36 patients from the 2013 to 2014 cohort, seven showed p53 overexpression, one showed Ki-67 overexpression, two showed serous tubal intraepithelial carcinoma, and three showed occult cancer. The detection rate of precursor lesions or cancer was 36.1% (13/36). In the analysis according to age, precursor lesions were more common in BRCA1 mutation carriers younger than 40 years old (66.7% vs. 20.0%). In BRCA2 mutation carriers, precursor lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of precursor lesions in BRCA1 mutation carriers. Conclusion Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers.

Aims: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. Methods: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. Results: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. Conclusions: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.

The purpose of this study was to evaluate the surgical feasibility of and survival outcome after laparoscopy in obese Korean women with endometrial cancer which has recently been increasing. We reviewed the medical records of the patients treated at our medical institution between 1999 and 2012. The patients were divided into three groups, non-obese (Body Mass Index [BMI]

본고는 유엔주도 평화유지활동(UNPKO)과 비유엔주도(다국적군, MNF) 평화활동을 포괄하는 국제평화유지활동의 변화양상을 살펴보고, 이들 활동에 있어서의 한국의 역할을 고찰한다. 또한 본고는 이 두 유형의 평화활동이 그 성과 면에서 사실상 별다른 차이가 없음에도 불구하고, 왜 한국에서 이들에 대한 평가가 엇갈리는지를 분석하고자 한다. 유엔PKO에 대해서는 이해부족이나 무관심의 문제가 있기는 하나 상대적으로 참여에 대해 별다른 반대가 없는데 비해, MNF의 경우는 사회분열을 야기할 정도로 찬반론이 거센 상황이 종종 야기된다. 특히 MNF 파병에 반대하는 경우는 한국이 국제평화나 인도적 이유에서가 아니라 미국의 압력에 따라 ‘전쟁놀음’의 꼭두각시 노릇을 한다는 식의 강력한 비난이 쏟아지기도 한다. 그렇다면 한국의 국제평화활동에 대한 평가는 왜 이렇듯 ‘불일치’ 혹은 ‘PKO 격차’ 현상을 일으키는 것일까? 어떻게 이들 격차를 좁힐 수 있을까? 이에 대한 해답을 도출하기 위해 본고는 3가지 논지를 분석하고자 한다. 첫째, 유엔 헌장에도 명기되어있듯이 두 유형의 평화활동은 세계평화와 안전을 지키기 위해 상호 보완적이다. 둘째, 한국의 PKO 격차현상은 해외파병에 대한 대중인식에 커다란 영향을 받고 있으며 정치지도자의 성향도 일정 정도 이에 영향을 끼친다. 특히 대중의 태도나 반응은 정치적 목적에 이용되기도 한다. 셋째, 두 유형의 평화유지활동을 동시에 추구하는 것이 세계안보뿐 아니라 국익향상에도 기여한다는데 대한 국민적 합의가 필요한데, 이를 위해 정책결정자, 오피니언리더, 그리고 일반대중이 전략적, 실제적 이해관계와 윤리적, 규범적 고려를 동시에 추구하는 신중함과 지혜를 모아야 한다.

The objective of this study was to assess whether the ratio of upper abdomen (UA) to lower abdomen (LA) (relative to the umbilicus) standardized fluorine 18 fluorodeoxyglucose uptake, as measured by preoperative positron emission tomography and computed tomography, is predictive of recurrence, survival, and suboptimal cytoreduction (residual tumor1.0 cm) in advanced-stage ovarian cancer (AOC).Positron emission tomography/computed tomography before surgical staging was performed in 159 AOC patients. The ratio between the highest maximum standardized uptake value (SUV(max)) in the UA and the LA was expressed as UA/LA SUV(max). Clinicopathological characteristics and follow-up information were collected retrospectively. Cox proportional hazards analysis was used to identify prognostic factors for recurrence and survival. Logistic regression analysis was used to identify predictors of suboptimal cytoreduction.The median age and follow-up period were 55 years (range, 27-80 years) and 32 months (range, 1-92 months), respectively; 133 and 26 patients had stage III and IV disease, respectively. There were 120 and 54 cases of recurrence and disease-specific death, respectively. Multivariate analysis showed that recurrence was associated significantly with high UA/LA SUV(max) (P0.05; hazard ratio [HR], 4.902; 95% confidence interval [CI], 2.521-9.531) and suboptimal cytoreduction (P0.05; HR, 2.431; 95% CI, 1.561-3.788), and that disease-specific death was significantly associated with high UA/LA SUV(max) (P0.05; HR, 2.777; 95% CI, 1.270-6.075), suboptimal cytoreduction (P0.05; HR, 1.951; 95% CI, 1.080-3.524), and histology (P0.05; HR, 4.134; 95% CI, 1.676-10.196). Upper abdomen/lower abdomen SUV(max) was the only independent predictor of suboptimal cytoreduction (P0.05; odds ratio, 4.644; 95% CI, 1.676-12.862).High preoperative UA/LA SUV(max) was significantly associated with poor prognosis and may be predictive of suboptimal cytoreduction in AOC. This parameter may be considered in the treatment of AOC patients.

Objective The reciprocal regulation of c-Src and STAT3 activation seems to be associated with the poor response to c-Src inhibitors of ovarian cancer. This study aims to investigate inhibition of cell proliferation and enhancement of the cytotoxic effect of chemotherapeutic agents via simultaneous suppression of c-Src and STAT3 in ovarian cancer cell lines. Study design Specific siRNAs targeting c-Src and STAT3 were produced and transfected into an SKOV3 ovarian cancer cell line. We confirmed the downregulation of c-Src and STAT3 mRNAs by reverse transcriptase polymerase chain reaction. MTT assay was used to assess cytotoxicity following cisplatin administration. Protein expression level was evaluated by Western blot. Results Cell growth was significantly inhibited by c-Src or STAT3 siRNA. Cytotoxicity was not increased in cisplatin-treated SKOV3 by c-Src siRNA only or STAT3 siRNA only, but cell viability was decreased significantly in cisplatin-treated cells after simultaneous transfection with c-Src and STAT3 siRNAs. Specifically, the viability was significantly decreased from 30% to 55% within the IC50 concentration following simultaneous transfection with c-Src and STAT3 siRNAs, particularly after 72 h. Src and survivin protein expression level was significantly decreased at 72 h after transfection of c-Src and STAT3 siRNAs. Conclusions This study has demonstrated the principle that the simultaneous suppression of c-Src and STAT3 inhibits the growth of epithelial ovarian cancer cells and seems to enhance the cytotoxicity of chemotherapeutic agents in ovarian cancer.

Objective Laparoscopic management in patients with malignant nonepithelial ovarian tumors (MNEOTs) was unpopular owing to the solid nature and relatively large size of the tumors. The purpose of this study was to evaluate the role of laparoscopy for MNEOTs. Methods Between January 1989 and September 2010, 28 patients with MNEOTs underwent laparoscopic surgery at our institution. These patients’ clinicopathologic data were retrospectively reviewed from medical records. Results Cases included 20 sex cord–stromal tumors (18 granulosa cell and 2 Sertoli-Leydig cell) and 8 malignant germ cell tumors (4 dysgerminomas, 2 immature teratomas, 1 choriocarcinoma, and 1 yolk sac tumor). The patients’ median age was 27 years (range, 16–35 years) for those with malignant germ cell tumors and 42 years (range, 7–57 years) for those with stromal tumors. The median primary tumor diameter was 10.4 cm (range, 3.3–20.8 cm). Laparoscopic pelvic and para-aortic lymph node dissections were performed in 9 cases. Laparoscopic removal of primary tumor and omentectomy were performed in 26 and 6 cases, respectively. Hand-assisted laparoscopic surgery was performed for one huge tumor that could not be entered into the endobag. The median operating time was 102 minutes (range, 45–300 minutes), and the median postoperative hospital stay was 3 days (range, 2–10 days). All patients had stage I disease. Five patients received adjuvant chemotherapy, and the median interval to chemotherapy was 14 days (range, 2–21 days). No intraoperative complication or conversion to laparotomy was observed. Only one postoperative febrile morbidity occurred. The median follow-up was 34.5 months (1–185 months). One patient developed recurrence, which was treated with chemotherapy. No patient died of their disease. Conclusion This is the first case series report of laparoscopic surgery for MNEOTs. Laparoscopic management seems feasible and safe without compromising survival. With additional evidence, laparoscopic surgery could be a safe therapeutic option for management of early-stage MNEOTs.

Objective Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. Methods Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. Results In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825–0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. Conclusion We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.

Mucinous adenocarcinoma is an uncommon type of endometrial adenocarcinoma for which precursor lesions have yet to be clarified. During a review of noncancerous endometrial lesions in postmenopausal women, we found that mucinous endometrial glands showed variable degrees of epithelial changes that ranged from the formation of simple tubular glands to the formation of complex glands with papillary tufts, and some of the glands with papillary tufts were architecturally similar to low-grade mucinous adenocarcinomas. Based on histological similarities, we have postulated that mucinous metaplasia could be a precursor lesion of mucinous adenocarcinoma. To explain the pathogenetic significance of endometrial mucinous metaplasia, we analyzed the immunohistochemical expression of ER, PR, MKI67, PTEN, β-catenin, P16(INK4A), TP53, and PAX2 in 21 endometrial mucinous metaplasias, screened for KRAS (n=16) and PTEN (n=14) mutations, and compared expression patterns between samples with simple mucinous glands, those with complex glands having intraglandular papillary tufts, and endometrioid adenocarcinomas. Compared with the surrounding flat mucinous epithelium and simple mucinous metaplasia, the intraglandular papillary tufts associated with papillary mucinous metaplasia were characterized by selectively decreased expression of PAX2 (P=0.029) and PR (P

Background and Purpose: Ovarian cancer is the most frequent cause of death from gynecologic malignancy. Recently, immunotherapies have been suggested as ways to treat this malignancy. However, the ideal of immunotherapy has not been realized yet in ovarian cancer patients. Therefore, we investigated effects of monocyte-derived dendritic cells (mono DCs) and new-generation DCs subset (new DCs) on an ID8 orthotropic mouse model of ovarian cancer. Methods: Mono DCs were prepared from bone marrow of C57BL/6 mice. We isolated monocyte from bone marrow by monocyte isolation kit. Isolated monocyte was incubated for 7 days with IL-4 and GM-CSF. In addition, monocytes were pulsed with LPS and ID8 tumor lysate while incubating. Likewise new DCs were isolated from bone marrow of C57BL/6 mice. We isolated lineage negative cells from bone marrow using lineage cell depletion kit. Isolated cells were incubated with IL-4 and GM-CSF; also the cells were pulsed by ID8 tumor lysate and Rg3, which is a ginsenoside. Orthotropic model of ID8 was made on C57BL/6 mice. We injected 5x106 cells into peritoneal cavity. 4 weeks after cell injection, mice were grouped into three groups, which were vehicle, mono DCs and new DCs. Mice were injected with mono DCs and new DCs. 5x106 cells of DCs were injected 1 time/week for three weeks. One week later, mice were sacrificed and organs were harvested such as peritoneum, phren, ovary and tumor mass for histologic analysis. Results: DCs treated groups showed lower ascites formation than vehicle group. Ascites were fewest in new DCs group. Survival rate was lowest in vehicle group. Each survival rate is 0% in vehicle, 63% in new DCs and 80% in mono DCs. Also tumor growth at ovary was more decreased in mono DCs and new DCs group. In addition, mono DCs-treated mice showed low level of metastasis to other organs. Conclusion: Immunotherapy with dendritic cells showed inhibition of tumor growth and metastasis on mouse ovarian cancer. These results indicated that DCs treatments are able to be a potential therapy for ovarian cancer. It also could have synergy with the combined treatment of existing anticancer drugs. However, there are several limitations such as a relatively high dose of DCs and the procedure of isolating DCs needed large amount of bone marrow. We will continue to study and improve these issues. Citation Format: Min-Je Kim, Joo-won Kim, Ju-hyun Kim, Young-Jae Lee, Shin-Wha Lee, Yong-Man Kim. Immunotherapy with dendritic cells inhibited tumor growth on an ID8 orthotropic mouse model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 119.

Background: The analysis of single parameters alone may not provide sufficient insights about complex immune system-tumor interactions. This study is to validate the immune contexture as prognostic biomarkers in high-grade serous ovarian cancer (HGS-OC) and to find new era of immunoscore in HGS-OC. Methods: We collected FFPE samples from 187 patients with HSOC and produced TMA samples. We accomplished the OPAL multiplex IHC assay for the quantitative analysis of immune markers, including CD4, CD8, CD20, FoxP3, PD-L1, and CK. Multiplex Biomarker Imaging and inForm® Image Analysis Software was used. Results: FIGO stage III and IV patients were 84.5% (158/187). The optimal debulking surgery was done in 66.8% (125/187). The 3-year disease-free survival and 5-year overall survival were 35.1% and 50.0%, respectively. Any single marker was not related to the survival, including CD8, FoxP3, and PD-L1. However, high CD8:FoxP3 and CD8:PD-L1 ratios were correlated with good survival. In Cox regression model, the risk factors for HGS-OC survival were FIGO stage (HR 1.784, 95% CI: 1.295-2.457, p Conclusion: These findings indicate that although any single immune marker is not related to the survival, CD8:FoxP3 and CD8:PD-L1 ratios provide the positive correlation with the prognosis in HGS-OC; especially, CD8:PD-L1 ratio is prognostic biomarker that is comparable to clinical biomarkers. The next study for immunoscore is necessary to define immunoscore in ovarian cancer. Citation Format: Shin-Wha Lee, Min-Je Kim, Ju-hyun Kim, Young-Jae Lee, Yong-Man Kim, Yong-Man Kim. Immunoscore as prognostic biomarkers in patients with epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5703.

This study evaluated the efficacy and toxicity of belotecan (CKD-602), a new camptothecin analogue topoisomerase i inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. Data from 63 patients who had been treated with intravenous belotecan (0.5 mg/m(2)/day), administered for 5 days every 3 weeks at a single institute in Seoul, Korea, were collected retrospectively. The overall response rate was 30.2% including 9 patients with complete remission (CR) and the progression free survival was a median of 6.5 (0.7 - 29.7) months. The platinumsensitive group had a significantly higher response rate and longer progression-free survival more than the platinum-resistant group. The most common adverse effect of belotecan was hematologic toxicity which was tolerable. As a single chemotherapy agent, belotecan was effective in treating recurrent or refractory epithelial ovarian cancer, and had acceptable toxicity. Further studies of the efficacy of belotecan in combination with platinum or the other agents are warranted.

Background: PARP inhibitors have demonstrated clinically meaningful increase in progression-free survival as a single agent in women with recurrent ovarian cancer following a response to platinum-based chemotherapy. However, there still needs more improvement in efficacy because PARP inhibitors have comparatively low efficacy in non-germline BRCA-mutated patients. We aimed to develop a novel PAPR inhibitor that may have potent antitumor efficacy against the non-germline BRCA-mutated patients in addition to the germline BRCA-mutated patients. Here, we describe a novel selective PARP inhibitor IDX-1197. Materials and Methods: We conducted in vitro assays to evaluate IDX-1197 as a PARP inhibitor using PARP enzyme assay and PARP-catalytic inhibition assay in Hela cells. We evaluated in vivo efficacy of IDX-1197 against ovarian and breast tumor growth using patient-derived xenograft models. To investigate PARP inhibition in tumors, tumor PAR levels were measured by ELISA in the PDX models. Results: In enzyme assay, IDX-1197 potently inhibited PARP1 and PARP2 activities with IC50 values of 1.4 nM and 1.0 nM, respectively. By contrast, IDX-1197 was not sensitive to PARP5A (Tankyrase-1), which belongs to the PARP family (IC50>10 μM). In DNA damage-induced Hela cells, IDX-1197 significantly inhibited PARP1-mediated PAR expression (EC50 = 0.5 nM). In the germline BRCA1-mutated ovarian cancer PDX model, oral administration of IDX-1197 exhibited significant PAR inhibition (>90%) in tumor tissues until 24 hr post dose. IDX-1197 also dose-dependently led to potent tumor growth inhibition compared to Olaparib treatment group. Furthermore, IDX-1197 showed improved antitumor activity against breast cancer PDX models, which included both germline BRCA-mutated and non-germline BRCA-mutated models. In these models, IDX-1197 exhibited greater tumor growth inhibition compared with olaparib and/or niraparib. Conclusions: IDX-1197 is a highly potent and selective inhibitor of PARP1/2 with significant in vitro and in vivo activities in multiple cancer models. These preclinical data demonstrate the efficacy of IDX-1197, which has the potential for a best-in-class profile, in non-germline BRCA-mutated patients as well as BRCA-mutated patients. Based on these findings, IDX-1197 has entered clinical phase 1 trial in Korea. Funded by National OncoVenture. Citation Format: Myongjae Lee, Joon-Tae Park, Ji-hun Yang, Dohee Kim, In-Gyu Je, Yoon Suk Lee, Jinah Jeong, Dong Keun Song, Soobong Park, Hong-Sub Lee, Yong-Man Kim, Shin-Wha Lee, Dong Woo Kang, Ha-Young Lee, Jung Yong Kim, Sungsook Lee, Nam Seok Baek, Jae-Hoon Kang. Development of IDX-1197, a novel, selective, and highly potent PARP inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A106.

Objective. To investigate the efficacy of conization followed by conservative management for treating stage IA1 microinvasive carcinoma of the uterine cervix. Design/Setting. Retrospective study. Population. Seventy-five patients treated for stage IA1 microinvasive carcinoma of the cervix. Patients underwent conization followed by hysterectomy (Group 1, 53 patients), or were followed by conservative management (Group 2, 22 patients). Methods. Medical and histopathological record review. Results. For Group 1, pathology results showed that 30 had no residual tumor, one had cervical intraepithelial neoplasia (CIN) I, 11 had CIN III/cervical carcinoma in situ (CIS), nine had microinvasive carcinomas, and one had an invasive carcinoma (outcome for one patient not recorded). For Group 2, secondary procedures involved only cervical smears for 12 (48%) patients, of whom nine had normal cytology, one had low-grade squamous intraepithelial lesion and two had high-grade squamous intraepithelial lesions. For 13 (52%) patients in Group 2, secondary procedures involved repeat conization on whom six had no residual tumor, one had CIN II, four CIN III/CIS, and two microinvasive carcinoma and a negative resection margin. Therefore, conization followed by conservative management was an effective treatment for 90.9% (20/22) of Group 2. In neither group was recurrence recorded. There was no relation between lymphovascular invasion and follow-up cytology or pathology results, or between resection margin status and follow-up examination results. Conclusion. Conization alone with careful follow-up appears to be an effective and safe treatment for patients with stage IA1 microinvasive carcinoma of the uterine cervix, regardless of resection margins status or lymphovascular invasion.

Objective To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. Study Design A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. Results During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). Conclusion Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients.

Domestic politics combined with strategic repositioning toward the U.S. set back ties between Japan and South Korea in 2004–05. Despite the North Korean nuclear crisis and the challenge of shifting great power relations in Asia, as well as closer economic and cultural bilateral ties, politicized forces are pulling the two countries apart.