Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial

Overall survival; Olaparib; Ovarian cancerSupervivencia global; Olaparib; Cáncer de ovario avanzadoSupervivència global; Olaparib; Càncer d'ovari avançatPURPOSE In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting. METHODS This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up. RESULTS The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups. CONCLUSION Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up

Long-term recurrence-free survival in a patient with stage IVB uterine carcinosarcoma

Uterine carcinosarcomas are rare and highly aggressive tumors with a poor prognosis. Due to early metastasis and disease progression, it is known to be far more aggressive than matched grade 3 endometroid endometrial carcinomas. Five-year survival for stage IV is reported to be 10% and overall survival for stage IVB is expected to be very poor. The authors report one case after experiencing long-term survival (over 5 years) for stage IVB carcinosarcoma of uterus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed to 56 year old patient for uterine myoma. On pathology report, uterine carcinosarcoma was diagnosed and image studies were performed. With the impression of stage IVB uterine carcinosarcoma, 6 cycles of chemotherapy (ifosfamide and cisplatin) was conducted as adjuvant. Up to recently (over 5 years), she maintains good performance scale without evidence of tumor recurrence or disease progression

Interaction of testisin with maspin and its impact on invasion and cell death resistance of cervical cancer cells

AbstractPrevious studies have shown that testisin promotes malignant transformation in cancer cells. To define the mechanism of testisin-induced carcinogenesis, we performed yeast two-hybrid analysis and identified maspin, a tumor suppressor protein, as a testisin-interacting molecule. The direct interaction and cytoplasmic co-localization of testisin with maspin was confirmed by immunoprecipitation and confocal analysis, respectively. In cervical cancer cells, maspin modulated cell death and invasion; however, these effects were inhibited by testisin in parallel experiments. Of interest, the doxorubicin resistance was dramatically reduced by testisin knockdown (P=0.016). Moreover, testisin was found to be over-expressed in cervical cancer samples as compared to matched normal cervical tissues. Thus, we postulate that testisin may promote carcinogenesis by inhibiting tumor suppressor activity of maspin.Structured summaryMINT-7712215, MINT-7712176: Testisin (uniprotkb:Q9Y6M0) binds (MI:0407) to Maspin (uniprotkb:P36952) by pull down (MI:0096)MINT-7712188: Testisin (uniprotkb:Q9Y6M0) and Maspin (uniprotkb:P36952) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7712115: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by two-hybrid (MI:0018)MINT-7712162, MINT-7712128: Maspin (uniprotkb:P36952) physically interacts (MI:0915) with Testisin (uniprotkb:Q9Y6M0) by anti bait co-immunoprecipitation (MI:0006)MINT-7712147: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by anti tag co-immunoprecipitation (MI:0007

Benign Metastasizing Leiomyoma with Multiple Lymph Node Metastasis: A Case Report

This is a case report about benign metastasizing leiomyoma with multiple lymph node metastasis. A 34-year-old woman received an abdominal myomectomy for a suspicious leiomyoma. On the pathology report, atypical leiomyoma was suspected. Due to the suspicion of multiple lymph node metastasis on pelvis computed tomography (CT) 1 year after the operation, she was transferred to the Samsung Medical Center on October, 2009 for further work up. According to original slide review, it was determined to be a benign leiomyoma with a mitotic count <5/10 high-power fields, little cytological atypia and no tumor cell necrosis. Additional immunostaining was done. Multiple lymph node metastasis and a small lung nodule were identified on positron emission tomogarphy-CT and chest CT. Extensive debulking surgery and diagnostic video-assisted thoracoscopic surgery (VATS) wedge resection were subsequently done. Metastatic lesions were reported to have a histology similar to that of the original mass. VATS right upper lobectomy with mediastinal lymph node dissection was performed because of the pathology result of VATS (adenocarcinoma). She started taking an aromatase inhibitor (Letrozole®) and there was no evidence of recurrence of disease on an imaging study and no post-operative complications until recently

Chemo-resistant choriocarcinoma metastatic to colon cured by low-anterior resection

The role of surgery in the treatment of patients with metastatic choriocarcinoma has diminished. We present a case of chemo-resistant metastatic choriocarcinoma salvaged by surgery. A 48-year-old patient presented with uterine perforation and severe intractable hemorrhage, and histological examination revealed a choriocarcinoma. After 6 years of disease-free state, recurrence occurred in the rectosigmoid colon. Seven cycles of EMACO chemotherapy was administered, and the human chorionic gonadotropin level was normalized. Three months after the chemotherapy, the rectosigmoid colon metastasis progressed. Low anterior resection with lymphadenectomy up to the level of the inferior mesenteric artery was conducted. After the operation, the human chorionic gonadotropin level decreased to within the normal range. There has been no evidence of disease for 13 months since the operation. Local resection of metastases seems to play a significant role in curing the disease in a small subset of patients

Genomic Network-Based Analysis Reveals Pancreatic Adenocarcinoma Up-Regulating Factor-Related Prognostic Markers in Cervical Carcinoma

We previously showed that PAUF is involved in tumor development and metastases in cervical cancer. This study was conducted to discover novel molecular markers linked with PAUF in cervical cancer using genomic network analysis and to assess their prognostic value in cervical cancer. Three PAUF-related genes were identified using in-silico network-based analysis of the open genome datasets. To assess the expression of these genes and their relationship to the outcome of cervical cancer, immunohistochemical analysis was performed using cervical cancer TMA. The associations of the identified proteins with clinicopathologic characteristics and prognosis were examined. AGR2, BRD7, and POM121 were identified as interconnected with PAUF through in-silico network-based analysis. AGR2 (r = 0.213, p &lt; 0.001) and POM121 (r = 0.135, p = 0.013) protein expression were positively correlated with PAUF. BRD7High and AGR2Low were significantly associated with favorable disease-free survival (DFS) (p = 0.009 and p &lt; 0.001, respectively), and in combination with PAUFHigh, even more significantly favorable DFS observed (p &lt; 0.001 for both). In multivariate analysis, AGR2High (HR = 3.16, p = 0.01) and BRD7High (HR = 0.5, p = 0.025) showed independent prognostic value for DFS. In a random survival forest (RSF) model, the combined clinical and molecular variable model predicted DFS with significantly improved power compared with that of the clinical variable model (C-index of 0.79 vs. 0.75, p &lt; 0.001). In conclusion, AGR2 and BRD7 expression have prognostic significance in cervical cancer and provide opportunities for improved treatment options. Genomic network-based approaches using the cBioPortal may facilitate the discovery of additional biomarkers for the prognosis of cervical cancer and may provide new insights into the biology of cervical carcinogenesis