Effect of Waiting Time from Pathological Diagnosis to Definitive Concurrent Chemoradiation for Cervical Cancer on Overall Survival / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effect of waiting time, from diagnosis to initiation of definitive concurrent chemoradiation (CCRT), on overall survival in cervical cancer patients. @*Materials and Methods@#Patients with cervical cancer who were treated with definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from initial pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in two groups (group 1 ≤ median, group 2 > median). Patients with a waiting time of more than 60 days were excluded. @*Results@#The median waiting time was 14 days (0-60). There were differences between group 1 and group 2 in age and chemotherapy regimens. However, no significant difference was found in the International Federation of Gynecology and Obstetrics stage, cell type, or the number of cycles of chemotherapy received during CCRT. A longer waiting time was associated with poorer overall survival on the Kaplan-Meier curve (group 1 vs. group 2, p=0.042). On multivariate analysis, intervals as either a continuous variable (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006 to 1.040; p=0.007) or a categorical variable (HR, 1.513; 95% CI, 1.073 to 2.134; p=0.018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival. @*Conclusion@#A shorter waiting time from pathological diagnosis to definitive CCRT showed benefit on overall survival. Our findings suggest that an effort to minimize waiting times should be recommended in cervical cancer patients who are candidates for CCRT.

Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features / 부인종양

Objective@#Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features. @*Methods@#A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model. @*Results@#Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7–97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003). @*Conclusion@#In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer. @*Materials and Methods@#We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed. @*Results@#We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.

Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer. @*Materials and Methods@#We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed. @*Results@#We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.

Pretreatment Lymph Node Metastasis as a Prognostic Significance inCervical Cancer: Comparison between Disease Status / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Lymph node metastasis (LNM) is the most significant prognostic factor in cervical cancerthat was recently incorporated into the International Federation of Gynecology and Obstetrics(FIGO) staging system. This study was performed to evaluate whether the prognosticsignificance of LNM differs according to disease status. @*Materials and Methods@#Patients with FIGO stage IB or higher cervical cancer who had pretreatment computedtomography and/or magnetic resonance imaging studies as well as long-term follow-upwere enrolled in this retrospective study. The hazard ratio (HR) of Cox regression was usedto determine the prognostic significance of LNM. The HRs were compared between the differenttumor groups (based on stage, histology, tumor size, primary treatment, age, parametriuminvolvement, and lymphovascular space invasion). @*Results@#A total of 970 patients treated between January 1999 and December 2007 were included.The pretreatment LNM had prognostic significance in patients with stage IB1/IIA (HR forprogression-free survival 2.10, p=0.001; HR for overall survival 1.99, p=0.005). However,the significance gradually decreased or disappeared with advancing stages. Similarly, theprognostic significance of the pretreatment LNM decreased with advancing disease status,including old age, parametrial involvement or lymphovascular space involvement. In contrast,the tumor size was associated with the prognostic significance of LNM with advancingstatus. The significance of the clinical LNM did not reflect the significance of the clinicalstage. In contrast, the tumor size, parametrial involvement, and significance of the pathologicLNM reflected the clinical stage. @*Conclusion@#In patients with cervical cancer, pretreatment LNM on imaging has different clinical significancedepending on the tumor status.

Long-term outcomes of single-port laparoscopic myomectomy using a modified suture technique

OBJECTIVE: To evaluate the long-term outcomes, including the pregnancy outcome and recurrence rate after single-port laparoscopic myomectomy (LM) using a modified suture technique with a Hem-o-lok clip (Choi's LM) and conventional 4-port LM.METHODS: A retrospective study of patients who underwent Choi's LM (n=55) and 4-port LM (n=102) in a single institutional hospital was conducted. Patients with <3 symptomatic myomas sized <10 cm each and operated on by a single surgeon were included. Recurrence was confirmed when a myoma measuring ≥3 cm was detected.RESULTS: The patients in both groups had similar demographic characteristics. Single (76.4% vs. 62.7%) and intramural (52.7% vs. 56.9%) tumors were commonly detected in both groups in the mean diameter (6.8±1.5 cm vs. 7.0±1.6 cm; P=0.40). In Choi's LM, 16 patients (29.1%) needed an additional port; those who were nulliparous and/or had a large leiomyoma more frequently required an additional port (P=0.023 and 0.04, respectively). During a median follow-up period of 69 months, 17 patients (7.1% vs. 14.6%) had recurrence. The size of dominant myomas at recurrence was significantly smaller in patients who underwent Choi's LM (3.4±0.7 cm vs. 5.7±2.4 cm; P=0.004). All 13 patients in both groups who successfully conceived had a full-term delivery. No major complications occurred during pregnancy.CONCLUSION: Although an additional port was frequently used, the long-term outcomes of patients who experienced recurrence and pregnancy after Choi's LM were acceptable. Considering its usability, Choi's LM is feasible for the treatment of uterine leiomyoma.

Combination of a pulmonary recruitment maneuver and intraperitoneal bupivacaine for the reduction of postoperative shoulder pain in gynecologic laparoscopy: a randomized, controlled trial

OBJECTIVE: To compare the efficacy of a pulmonary recruitment maneuver using lower airway pressure (30 cm H2O) and intraperitoneal bupivacaine, alone or in combination, for reducing shoulder pain after gynecologic laparoscopy.METHODS: A prospective controlled study was performed in a teaching hospital with patients who underwent elective gynecologic laparoscopic surgery. Two hundred eighty-seven patients were randomized into 1 of 4 groups: group A, placebo; group B, intraperitoneal instillation of bupivacaine; group C, CO2 removal by a pulmonary recruitment maneuver; group D, combination of intraperitoneal bupivacaine and pulmonary recruitment maneuver. The interventions were performed at the end of surgery. Shoulder pain was recorded on a visual analog scale (VAS) at 1, 6, 12, and 24 hours postoperatively.RESULTS: The overall incidence of shoulder pain was 49.8% and the incidence tended to gradually decrease from group A to group D (59.0% in group A, 54.8% in group B, 44.4% in group C, and 41.5% in group D; P=0.026). In addition, the VAS scores gradually decreased from group A to D, although a statistically significant difference was only found at 6 hours postoperatively (P=0.03). There were no complications related to the interventions.CONCLUSION: The combination of a pulmonary recruitment maneuver with intraperitoneal bupivacaine significantly reduced shoulder pain after gynecologic laparoscopy.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01039441

Optimal cutoff age for predicting prognosis associated with serous epithelial ovarian cancer: what is the best age cutoff? / 부인종양

OBJECTIVE: Elderly age is one of the poor prognostic factors in epithelial ovarian cancer (EOC), but the optimal age cut-off is not known. The present study sought to identify the ideal age cutoff that represents a negative prognostic factor in EOC, considering the geriatric assessment. METHODS: Hazard ratios (HRs) with p-values were calculated using all possible age cutoffs with stage, histology, grade, optimality and comorbidities as covariates in multivariate Cox regression model. The trends of p-value and HR by age cutoff were further evaluated in a subgroup of histology and in The Cancer Genome Atlas (TCGA) dataset. In addition, propensity score-matching analysis using the identified age cutoff was performed. RESULTS: An age of 66 years was shown to be the most significant cutoff for defining old age with independent prognostic power (HR=1.45; 95% confidence interval=1.04–2.03; p=0.027). This result was also observed with the analyses of serous histology subgroup and with the analysis of a TCGA dataset with serous EOC. In survival analysis, patients aged ≥66 years had significantly worse overall survival compared with younger individuals (56 months vs. 87 months; p=0.006), even following propensity score matching (57 vs. 78 months; p=0.038). CONCLUSION: An age of 66 years is the best cutoff to define elderly age in serous EOC patients considering the geriatric assessment, and this information can be used in the administration of individualized therapies in elderly EOC patients.

Six months response rate of combined oral medroxyprogesterone/levonorgestrel-intrauterine system for early-stage endometrial cancer in young women: a Korean Gynecologic-Oncology Group Study / 부인종양

OBJECTIVE: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. METHODS: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. RESULTS: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as “EC” by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (ĸ=0.55). CONCLUSION: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594879

Prediction of survival outcomes in patients with epithelial ovarian cancer using machine learning methods / 부인종양

OBJECTIVES: The aim of this study was to develop a new prognostic classification for epithelial ovarian cancer (EOC) patients using gradient boosting (GB) and to compare the accuracy of the prognostic model with the conventional statistical method. METHODS: Information of EOC patients from Samsung Medical Center (training cohort, n=1,128) was analyzed to optimize the prognostic model using GB. The performance of the final model was externally validated with patient information from Asan Medical Center (validation cohort, n=229). The area under the curve (AUC) by the GB model was compared to that of the conventional Cox proportional hazard regression analysis (CoxPHR) model. RESULTS: In the training cohort, the AUC of the GB model for predicting second year overall survival (OS), with the highest target value, was 0.830 (95% confidence interval [CI]=0.802–0.853). In the validation cohort, the GB model also showed high AUC of 0.843 (95% CI=0.833–0.853). In comparison, the conventional CoxPHR method showed lower AUC (0.668 (95% CI=0.617–0.719) for the training cohort and 0.597 (95% CI=0.474–0.719) for the validation cohort) compared to GB. New classification according to survival probability scores of the GB model identified four distinct prognostic subgroups that showed more discriminately classified prediction than the International Federation of Gynecology and Obstetrics staging system. CONCLUSION: Our novel GB-guided classification accurately identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method. This approach would be useful for accurate estimation of individual outcomes of EOC patients.

Prognostic factors for recurrence and survival in uterine leiomyosarcoma: Korean single center experience with 50 cases

OBJECTIVE: The aim of this study was to determine the possible prognostic factors in patients with uterine leiomyosarcoma (LMS). METHODS: This study retrospectively investigated 50 patients with uterine LMS treated at the Samsung Medical Center between 2001 and 2017. To analyze the prognostic significance of factors for recurrence-free survival (RFS), overall survival (OS), and survival after recurrence, the log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis. RESULTS: Of the 50 patients, 30 (60.0%) experienced recurrence and 16 (32.0%) died within a median follow-up period of 21 (range, 3–99) months. Multivariate analysis revealed that older age, absence of residual tumor after surgery, lower mitotic count, and a history of adjuvant radiotherapy at first treatment were significantly associated with better RFS. Presence of residual tumor after surgery and severe nuclear atypia were associated with poor OS. In the analysis of survival after recurrence, hematogenous recurrence, severe nuclear atypia, and presence of residual tumor at primary surgery were significantly associated with worse prognosis. Notably, residual tumor status at primary surgery was associated with RFS, OS, and survival after recurrence. CONCLUSION: We demonstrated the possible prognostic factors for RFS, OS, and survival after recurrence for patients with LMS. These results may provide useful information for patients with LMS.

Prevalence and oncologic outcomes of BRCA1/2 mutation and variant of unknown significance in epithelial ovarian carcinoma patients in Korea

OBJECTIVE: BRCA mutational status is important in the management of ovarian cancer, but there is a lack of evidence supporting genetic testing in Asian populations. This study was performed to investigate the prevalence and prognostic outcomes of BRCA1/2 mutation and variant of unknown significance (VUS) in Korean patients diagnosed with epithelial ovarian cancer (EOC). METHODS: Among patients newly diagnosed with EOC between January 2007 and January 2017, those tested for germline BRCA1/2 mutation were studied, regardless of family history. Overall survival (OS) and progression-free survival (PFS) were compared between the patients with and without BRCA1/2 mutation and VUS. RESULTS: A total of 313 patients underwent BRCA testing: 88 patients had a BRCA1/2 mutation and 48 patients had a BRCA1/2 VUS (28.1% and 15.3%, respectively). There were no significant associations between BRCA1/2 mutation, BRCA1/2 wild-type, or BRCA1/2 VUS with age at diagnosis, histologic distribution, or residual disease status after primary cytoreductive surgery. BRCA1 mutation, including BRCA1 VUS, showed no difference in PFS or OS compared to BRCA1 wild-type. In contrast, BRCA2 mutation showed longer PFS than that of BRCA2 wild-type (P=0.04) or BRCA2 VUS (P=0.02). BRCA2 mutation, including BRCA2 VUS, did not show any difference in OS compared to BRCA2 wild-type. CONCLUSION: BRCA mutation and BRCA VUS had similar clinical characteristics and survival outcomes, except that BRCA2 mutation showed better PFS. The results of this study will help to understand the prognostic significance of BRCA mutation and VUS in Korean patients.

Practice guidelines for management of ovarian cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement / 부인종양

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.

Primary malignant melanoma of the uterine cervix treated with pembrolizumab after radical surgery: a case report and literature review

Malignant melanoma of the genital tract is a rare disease that is usually diagnosed by chance. When a definite diagnosis is delayed, the prognosis is very poor without standardized treatment. Herein, we describe a 40-year-old patient who presented with a history of bloody vaginal discharge for 7 months. Gynecological examination showed an exophytic, hard and pigmented cervical mass involving the upper vagina. The patient was diagnosed with cervical melanoma after a punch biopsy and underwent a radical hysterectomy, upper vaginectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. After surgeries, the patient underwent 2-cycles of adjuvant immunotherapy with pembrolizumab, but died within 8 months. In this report, treatment with pembrolizumab after radical surgery was not effective for this patient who had a primary cervical melanoma that metastasized to bone and lung tissue. We do not know why pembrolizumab was ineffective for this patient, but there are several possible explanations; further research is needed.

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer / 부인종양

OBJECTIVE: We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. METHODS: The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. RESULTS: Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3–164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. CONCLUSION: Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease.

Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea

OBJECTIVE: Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. METHODS: The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. RESULTS: A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (β-hCG) at diagnosis was 190.9 mIU/mL. Five (83.3%) patients presented with irregular vaginal bleeding and one (16.7%) had amenorrhea. All patients had disease confined to the uterus without metastasis at diagnosis and were successfully treated by hysterectomy alone. All of them were alive without disease during the follow-up period. CONCLUSION: In this study, we observed low level serum β-hCG titer and irregular vaginal bleeding with varying interval after antecedent term pregnancy were most common presenting features of PSTT. In addition, we demonstrated hysterectomy alone was successful for the treatment of stage I disease of PSTT.

Retrospective study of combination chemotherapy with etoposide and ifosfamide in patients with heavily pretreated recurrent or persistent epithelial ovarian cancer

OBJECTIVE: This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). METHODS: Patients with recurrent or persistent EOC who had measurable disease and at least one chemotherapy regimen were to receive etoposide at a dose of 100 mg/m²/day intravenous (IV) on days 1 to 3 in combination with ifosfamide 1 g/m²/day IV on days 1 to 5, every 21 days. RESULTS: From August 2008 to August 2016, 66 patients were treated with ETI regimen. Most patients were heavily pretreated prior to ETI: 53 (80.3%) patients had received 3 or more chemotherapy regimens. The response rate (RR) of ETI chemotherapy was 18.2% and median duration of response was 6.8 months (range, 0–30). Median survival of all patients was 5 months at a median follow up of 7.2 months. Platinum-free interval (PFI) more than 6 months prior to ETI has statistically significant correlation with overall survival (OS; 9.2 vs. 5.6 months; P=0.029) and RR (34.5% vs. 5.4%; P < 0.010). However, treatment free interval before ETI, number of prior chemotherapy regimen, and optimality of primary surgery did not show significant difference for RR or OS. Grade 3 or 4 hematologic toxicities were observed in 7 cases (3%) of the 232 cycles of ETI. CONCLUSION: The ETI combination regimen shows comparatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC patients with more than 6 months of PFI after last platinum treatment.

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. MATERIALS AND METHODS: We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation, we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. RESULTS: We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. CONCLUSION: Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis / 부인종양

OBJECTIVE: The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC). METHODS: This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery. RESULTS: Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p < 0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant. CONCLUSION: CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor.

Catamenial hemoptysis accompanied by subcutaneous endometriosis treated with combination therapy

Extra pelvic endometriosis is considered to be rare. This paper reports a case of catamenial hemoptysis accompanied by subcutaneous endometriosis in 26-year-old woman. A computed tomography scan of the chest revealed a focal ground-glass opacity lesion in the posterior segment of the right upper lobe. Histopathology confirmed the diagnosis of endometriosis of right lung and concurrent subcutaneous endometriosis. She was treated with surgical resection of the endometriosis lesions on two different sites and perioperative gonadotropin-releasing hormone agonist therapy. The 6-month follow-up after combination treatment showed no recurrence. Though long-term follow-up result is needed, aggressive treatment using combination treatment (surgery and perioperative medication) should be considered for symptomatic extra pelvic endometriosis.