Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708)

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.ope

계엄령에 대하여 : 관동대지진을 상기한다는 것

오늘날 도쿄를 보면 불법입국한 다수의 삼국인, 외국인이 매우 흉악한 범죄를 반복하고 있습니다. 이미 도쿄의 범죄 양상은 과거와 달라졌습니다. 이런 상황에서 대단히 큰 재해가 발생했을 경우에는 크나큰 소요사건까지 예상되는 그런 상황입니다. 이와 같은 일에 대처하기에 우리 경찰의 힘만으로는 한계가 있습니다. 바로 그렇게 때문에, 그런 경우에 여러분에게 출동을 바라며, 재해의 구조뿐만 아니라, 역시 치안유지도 여러분의 커다란 목적으로 수행해 주셨으면 하고 기대하고 있습니다. 지난 2011년 3월 11일의 대지진 직후, 압도적인 지지로 재선하여 여전히 수상의 자리를 노리고 있는 이시하라 신타로(石原慎太郎) 도쿄 도지사가 육상자위대 앞에서 행한 이 발언을 현 상황을 생각하는 회로로서 확보해 두는 작업이 반드시 필요하다고 생각한다. 왜냐하면 이 발언은 현재 계속되고 있는 위기 속에서 현세화(現勢化)하고 있는 일본이라는 국가가 여전히 제국의 계보 속에 존재하고 있음을 보여 주기 때문이다. 또한 이시하라의 발언에서는 사법을 넘어선 군사적 폭력과 치안유지의 밀접한 관계가 범죄라는 사법적인 법적 규정을 근거로 등장하고 있다. 거기에서 법적 질서에 잠재하는, 법을 넘어선 무법의 국가폭력이 드러날것이다. 이 글에서 생각하고 싶은 것은 무법적인 폭력의 현세화이며, 그것은 우선 재해라는 위기상황과 관련되어 있다. 또한 뒤에서 구체적으로 검토하겠지만, 질서의 유지를 군사적으로 실현하는 비상사태야말로 계엄령이라는 문제에 다름 아니다. 그리고 이시하라의 발언이 과거 제국의 기억을 상기시켜 미래에의 경구가 되는 것도 계엄령이라는 문제와 깊이 관련되어 있다

Sprayable nanomicelle hydrogels and inflammatory bowel disease patient cell chips for development of intestinal lesion-specific therapy

All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.ope

Outcomes of Non-High Grade Serous Carcinoma after Neoadjuvant Chemotherapy for Advanced-Stage Ovarian Cancer: Single-Institution Experience

PURPOSE: Outcomes in patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied; however, there is limited information on responses to chemotherapy among patients with non-HGSC. The aim of this study was to compare the survival outcomes of patients with advanced-stage non-HGSC and HGSC treated with NAC. MATERIALS AND METHODS: This study was a retrospective analysis of patients with advanced-stage ovarian cancer treated at Yonsei Cancer Hospital between 2006 and 2017. The demographics, chemotherapy response, and survival rates were compared between patients with non-HGSC and those with HGSC. RESULTS: Among 220 patients who underwent NAC, 25 (11.4%) patients had non-HGSC histologic subtypes, and all received a taxane-platinum combination regimen for NAC. Patients with non-HGSC had lower baseline cancer antigen-125 levels (p<0.001), poorer response rates (p<0.001), lower rates of optimal cytoreduction (p=0.003), and poorer progression-free survival (PFS) (median PFS 10.3 months vs. 18.3 months; p=0.009) and overall survival (OS) (median OS 25.5 months vs. 60.6 months; p<0.001), compared to those with HGSC. In multivariate analysis, non-HGSC was a negative prognostic factor for both PFS [hazard ratio (HR), 3.19; 95% confidence interval (CI), 1.73-5.88] and OS (HR, 4.22; 95% CI, 2.07-8.58). CONCLUSION: In this study, poorer survival outcomes were observed in patients who underwent NAC for treatment of non-HGSC versus those treated for HGSC. Different treatment strategies are urgently required to improve survival outcomes for patients with non-HGSC undergoing NAC.ope

Impact of increased utilization of neoadjuvant chemotherapy on survival in patients with advanced ovarian cancer: experience from a comprehensive cancer center.

OBJECTIVE: The choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NAC) in advanced ovarian cancer remains controversial. We evaluated NAC use in our center before and after results from a randomized trial were published, with the aim to determine the impact of changes in the neoadjuvant strategy on survival in advanced-stage ovarian cancer. METHODS: We retrospectively investigated the clinical course of 435 patients with ovarian, tubal, or peritoneal carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV). According to the period of treatment, we stratified patients into a control group (n=216; diagnosed between 2006 and 2010; 83.8% underwent PDS) and a study group (n=219; diagnosed between 2011 and 2014; 48.9% received NAC followed by interval debulking surgery [IDS]). RESULTS: There were no between-group differences in age, body mass index, histology findings, or tumor grade. Compared to patients in the control group, those in the study group were more likely to receive NAC followed by IDS as first-line treatment (48.9% vs. 16.2%; p<0.001), cytoreductive surgery to no-residual disease (21.5% vs. 10.2%; p<0.001), or radical surgery (57.5% vs. 35.6%; p<0.001). However, there was no between-group difference in postoperative morbidity. Kaplan-Meier analysis showed no between-group differences in progression-free or overall survival (p=0.449 and 0.952, respectively). CONCLUSION: NAC incorporation resulted in increased optimal cytoreduction rates although no significant differences in survival outcomes were noted. NAC is advantageous for patients with high perioperative morbidity or unresectable disease.ope

Evaluation of various kinetic parameters of CA-125 in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy.

Various kinetic parameters of serum CA-125 have been reported to have better correlation with outcomes for patients treated with neoadjuvant chemotherapy (NAC). This study aimed to compare the available kinetic parameters of serum CA-125 in an external cohort of advanced-stage ovarian cancer. Using the cancer registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed 210 patients with advanced-stage ovarian cancer, treated with NAC followed by interval debulking surgery. We compared area under the receiver-operating characteristics curves (AUCs), false negative rate, and negative predictive value (NPV) using 10 different models for optimal cytoreduction and platinum resistance. In addition, we compared incremental AUC for progression-free survival (PFS) and overall survival (OS). No gross residual tumor was observed in 37.0% and residual tumors 0.6 for predicting optimal cytoreduction. After adjusting for age, BMI, disease stage, and histologic subtypes, all models had an AUC >0.70 for predicting platinum resistance. However, no model had a high enough NPV (highest value = 82.0%) to avoid chemotherapy futility. For survival outcomes, no model had an incremental AUC >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic parameters showed high accuracy in predicting optimal cytoreduction, platinum resistance, or survival in patients receiving NAC. For advanced-stage ovarian cancer treated with NAC, there is a need to discover reliable biomarkers to better stratify patient response groups for optimal treatment decision-makingope

Role of surgical therapy in the management of gestational trophoblastic neoplasia

OBJECTIVE: To evaluate the role of adjuvant surgical procedures in the management of gestational trophoblastic neoplasia (GTN). METHODS: In a retrospective review of medical records at the Severance Hospital, we identified 174 patients diagnosed with GTN between 1986 and 2006. Of the 174 patients, 129 (74%) were assigned to the nonmetastatic group, and 45 (26%) to the metastatic group; of the metastatic group patients, 6 were in the low-risk group and 39 were in the high-risk group. Thirty-two patients underwent 35 surgical procedures as part of the GTN treatment. The procedures included hysterectomy, lung resection, craniotomy, uterine wedge resection, uterine suturing for bleeding, salpingo-oophorectomy, pretherapy dilatation and curettage, adrenalectomy, nephrectomy, and uterine artery embolization. RESULTS: Of the 32 patients who underwent surgical procedures, 28 (87%) survived. Eleven patients underwent surgery for chemoresistant disease after receiving one or more chemotherapy regimens. Twelve patients underwent procedures to control tumor hemorrhage. Nine (81%) of 11 patients with chemoresistant disease survived, and 8 patients who underwent salvage surgery for chemoresistant disease received further chemotherapy. Of 21 patients who underwent hysterectomy, 19 (90%) achieved remission. All of three patients who had resistant foci of choriocarcinoma in the lung achieved remission through pulmonary resection. CONCLUSION: Adjuvant surgical procedures, especially hysterectomy and pulmonary resection for chemoresistant disease, as well as procedures to control hemorrhage, are pivotal in the management of GTN.ope

Early Assessment of Response to Neoadjuvant Chemotherapy with 18F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer

Purpose: The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. Materials and methods: Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. Results: A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). Conclusion: Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.ope

Pretreatment neutrophil-to-lymphocyte ratio and its dynamic change during neoadjuvant chemotherapy as poor prognostic factors in advanced ovarian cancer.

Objective: The purpose of this study was to determine the prognostic implications of the pretreatment neutrophil-to-lymphocyte ratio (NLR) and its dynamic change during chemotherapy in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy. Methods: We performed a retrospective analysis of 203 patients who underwent neoadjuvant chemotherapy prior to interval debulking surgery for advanced-stage ovarian cancer at Yonsei Cancer Hospital between 2007 and 2015. Pretreatment NLR was evaluated before starting neoadjuvant chemotherapy. Change in NLR was defined as the post-neoadjuvant NLR value divided by the initial value. The correlation of NLR and its dynamic change with chemotherapy response score, response rate, and recurrence was analyzed. Results: The NLR ranged from 0.64 to 22.8. In univariate analyses, a higher pretreatment NLR (>3.81) was associated with poor overall survival (OS), but not progression-free survival (PFS). Through multivariate analysis, high pretreatment NLR was shown to be an independent parameter affecting OS, but not necessarily PFS. Changes in NLR during chemotherapy were better predictors of PFS than baseline NLR. Patients with increased NLR during chemotherapy showed significantly poor PFS, and this change was an independent predictor of PFS. Conclusion: Pretreatment NLR and its dynamic change during chemotherapy may be important prognostic factors in patients who undergo neoadjuvant chemotherapy.ope

Pretreatment lymphocytopenia is an adverse prognostic biomarker in advanced-stage ovarian cancer

The aim of this study was to investigate the prognostic significance of lymphocytopenia in advanced-stage ovarian cancer. We retrospectively reviewed 506 patients with advanced-stage ovarian cancer at Yonsei Cancer Hospital. This study included two cohorts of patients: a neoadjuvant chemotherapy (NAC) group (N = 247) and a primary debulking surgery (PDS) group (N = 259). The absolute lymphocyte count was recorded before treatment. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff for defining lymphocytopenia in the NAC cohort and followed by multivariate analysis. Subsequently, lymphocytopenia was assessed in the PDS cohort by multivariate analysis. A further analysis was performed to evaluate the absolute lymphocyte count as a continuous variable. An absolute lymphocyte count of 1.49 × 109/L was determined as the cutoff for the ROC curve analysis in the NAC cohort, and the multivariate analysis revealed that lymphocytopenia was an independent prognostic factor for poor progression-free survival (PFS) [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.07-2.11] and overall survival (OS) (HR, 2.02; 95% CI, 1.21-3.40). In the PDS cohort, the multivariate analysis showed that lymphocytopenia was an independent prognostic factor for poor PFS (HR, 1.73; 95% CI, 1.20-2.49) and OS (HR, 1.87; 95% CI, 1.27-2.75). The absolute lymphocyte count was a significant factor when analyzed as a continuous variable in both the NAC and PDS cohorts. Pretreatment lymphocytopenia is an independent adverse prognostic factor in patients with advanced-stage ovarian cancer.ope