Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics / 부인종양

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer / 부인종양

Objective@#To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. @*Methods@#This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. @*Results@#Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. @*Conclusion@#Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer / 부인종양

Objective@#The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. @*Methods@#Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens.The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). @*Results@#Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration.Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). @*Conclusion@#The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib.

The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients / 부인종양

OBJECTIVE: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. METHODS: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. RESULTS: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. CONCLUSION: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model.

Unenhanced region on magnetic resonance imaging represents tumor progression in uterine carcinosarcoma / 부인종양

OBJECTIVE: Carcinosarcoma of the uterine corpus has a poor prognosis. Although pathological necrosis is a prognostic factor of endometrial cancer, the clinicopathological influences of an unenhanced region observed on magnetic resonance imaging (MRI) are inconclusive. The aim of our study was to determine the clinicobiological impact of the presence of an unenhanced region on MRI, which can represent necrosis, in uterine carcinosarcoma. METHODS: The clinicopathological factors of 29 patients diagnosed with uterine carcinosarcoma were assessed retrospectively. The percentage of the tumor that was unenhanced on MRI was determined. The clinicopathological factors related to the unenhanced regions were evaluated. The prognostic significance was assessed using the Kaplan-Meier method and Cox regression model. RESULTS: Although the presence of pathological necrosis was not a poor prognostic factor (p=0.704), unenhanced regions on MRI correlated with poor prognosis when the unenhanced regions in the tumor accounted for more than 10% of the total tumor (p=0.019). The percentage of unenhanced regions was positively correlated with stage (p=0.028; r=0.4691) and related to tumor size (p=0.086; r=0.3749). The Cox regression analysis indicated that the presence of lymph node (LN) metastasis and more than 10% of the tumor being unenhanced on MRI were prognostic factors of overall survival in the univariate analyses (p=0.018 and p=0.047, respectively). CONCLUSION: The unenhanced region on MRI, which represents pathological necrosis, reflects tumor progression, and semi-quantification of the region is useful to predict the prognosis in patients with uterine carcinosarcoma.

Groin lymph node detection and sentinel lymph node biopsy in vulvar cancer / 부인종양

OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.