Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial.

BACKGROUND: Treatment outcomes remain poor in recurrent platinum-resistant ovarian cancer. Enadenotucirev, a tumor-selective and blood stable adenoviral vector, has demonstrated a manageable safety profile in phase 1 studies in epithelial solid tumors. METHODS: We conducted a multicenter, open-label, phase 1 dose-escalation and dose-expansion study (OCTAVE) to assess enadenotucirev plus paclitaxel in patients with platinum-resistant epithelial ovarian cancer. During phase 1a, the maximum tolerated dose of intraperitoneally administered enadenotucirev monotherapy (three doses; days 1, 8 and 15) was assessed using a 3+3 dose-escalation model. Phase 1b included a dose-escalation and an intravenous dosing dose-expansion phase assessing enadenotucirev plus paclitaxel. For phase 1a/b, the primary objective was to determine the maximum tolerated dose of enadenotucirev (with paclitaxel in phase 1b). In the dose-expansion phase, the primary endpoint was progression-free survival (PFS). Additional endpoints included response rate and T-cell infiltration. RESULTS: Overall, 38 heavily pretreated patients were enrolled and treated. No dose-limiting toxicities were observed at any doses. However, frequent catheter complications led to the discontinuation of intraperitoneal dosing during phase 1b. Intravenous enadenotucirev (1×1012 viral particles; days 1, 3 and 5 every 28-days for two cycles) plus paclitaxel (80 mg/m2; days 9, 16 and 23 of each cycle) was thus selected for dose-expansion. Overall, 24/38 (63%) patients experienced at least 1 Grade ≥3 treatment-emergent adverse event (TEAE); most frequently neutropenia (21%). Six patients discontinued treatment due to TEAEs, including one patient due to a grade 2 treatment-emergent serious AE of catheter site infection (intraperitoneal enadenotucirev monotherapy). Among the 20 patients who received intravenous enadenotucirev plus paclitaxel, 4-month PFS rate was 64% (median 6.2 months), objective response rate was 10%, 35% of patients achieved stable disease and 65% of patients had a reduction in target lesion burden at ≥1 time point. Five out of six patients with matched pre-treatment and post-treatment biopsies treated with intravenous enadenotucirev plus paclitaxel had increased (mean 3.1-fold) infiltration of CD8 +T cells in post-treatment biopsies. CONCLUSIONS: Intravenously dosed enadenotucirev plus paclitaxel demonstrated manageable tolerability, an encouraging median PFS and increased tumor immune-cell infiltration in platinum-resistant ovarian cancer. TRIAL REGISTRATION NUMBER: NCT02028117.

High Expression of MYL9 Indicates Poor Clinical Prognosis of Epithelial Ovarian Cancer.

BACKGROUND: The prognosis of Epithelial Ovarian Cancer (EOC) is poor, but the prognostic biomarkers are neither sensitive nor specific. Therefore, it is very important to search novel prognostic biomarkers for EOC. OBJECTIVES: The present study aimed to investigate Myosin Light Chain 9(MYL9) expression in Epithelial Ovarian Cancer (EOC) tissues (including paraffin-embedded and fresh tissue samples) and its relationship with clinicopathological characteristics, as well as its potential prognostic value in patients with EOC. METHODS: Between March 2009 and December 2018, all of 184 paraffin-embedded cancer tissues from patients with EOC and 41 paratumor tissues, pathologically confirmed at the Memorial Hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, were collected for the present study and were assessed for MYL9 protein expression patterns using Immunohistochemistry (IHC). Furthermore, from August 2013 to November 2019, 16 fresh EOC tissues and their paired paratumor tissues, pathologically confirmed at the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were analyzed using Reverse-Transcription Quantitative PCR (RT-qPCR) to detect MYL9 mRNA expression levels. RESULTS: The results showed that MYL9 expression was higher in cancer tissues compared with that in paratumor tissues, and MYL9 overexpression was associated with shorter Recurrence Free Survival (RFS) and Overall Survival (OS) of EOC patients. Furthermore, multivariate Cox model analysis indicated that MYL9 overexpression was an independent poor survival prediction in patients with EOC. CONCLUSION: MYL9 is upregulated in EOC and may serve as a useful patent of prognostic biomarker in EOC, and it may demonstrate an important value for the clinical treatment and supervision of patients with EOC.

Cyclin-dependent kinase 9 (CDK9) predicts recurrence in Middle Eastern epithelial ovarian cancer.

BACKGROUND: Cyclin-dependent kinase 9 (CDK9) has been shown to play an important role in tumorigenesis of several malignancies. However, the expression of CDK9 in ovarian cancer from Middle Eastern ethnicity remains unknown. METHODS: A tissue microarray of 441 epithelial ovarian cancer (EOC) samples was used to study the expression of CDK9 immunohistochemically and their clinico-pathological associations were determined. Cox proportional hazards regression model was used for univariate and multivariate analysis of recurrence-free survival. RESULTS: CDK9 over-expression was noted in 56.2 % (248/441) of EOCs and was associated with adverse clinico-pathological parameters such as distant metastasis (p < 0.0001), stage IV tumors (p < 0.0001), tumor recurrence (p = 0.0105) and high Ki-67 index (p < 0.0001). Importantly, CDK9 over-expression was an independent predictor of poor recurrence-free survival (Hazard ratio = 1.51; 95 % confidence interval = 1.15-1.98; p = 0.0030). We also found that CDK9 outperforms Ki-67 as a predictor of tumor recurrence in EOC. CONCLUSIONS: Our results show that CDK9 expression correlates with markers of advanced disease in Middle Eastern EOC and is also a prognostic marker. CDK9 overexpression also identifies a subset of patients with highest likelihood of recurrence across the patient cohort. These patients may benefit from additional alternative therapies targeting CKD9.

PARP inhibition as frontline therapy in ovarian cancer.

Poly(ADP-ribose) polymerase (PARP) inhibitors have been rapidly integrated into clinical practice for women with ovarian cancer. Currently, PARP inhibitors are approved as frontline maintenance treatment for patients with and without BRCA-associated cancers, and they are listed by the National Comprehensive Cancer Network (NCCN) as a treatment option for all high-grade serous and endometrioid cancers with or without bevacizumab. PARP inhibitors are also approved as maintenance treatment following a response to platinum-based therapy in the recurrent setting, irrespective of biomarker status. Additionally, PARP inhibitors are approved as third-line treatment and beyond in lieu of chemotherapy for patients with BRCA-associated cancers, and as fourth-line treatment and beyond for patients with platinum-sensitive homologous recombination-deficient tumors. They are also listed by the NCCN in combination with bevacizumab for the treatment of patients who have platinum-sensitive recurrent disease. The first part of this 2-part review focuses on the changing paradigm of frontline therapy options resulting from the recent approvals of PARP inhibitors; the second part considers the role of PARP inhibition in recurrent ovarian cancer.

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy.

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo. Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

[Technical essentials and safety analysis of "rolling carpet" cytoreduction surgery in stage â ¢c epithelial ovarian cancer].

Objective: To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy （"rolling carpet" surgery） in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality. Methods: From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent "rolled carpet" CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of "rolled carpet" CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of "rolling carpet" CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups. Results: (1) Clinicopathological features: the age of patients in "rolling carpet" CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the "rolled carpet" CRS group, all patients （100%, 30/30） were performed optimal CRS, reaching completeness of cytoreduction score （CC score）, named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients （77%, 23/30） reached CC-0 score, 5 cases （17%, 6/30） reached CC-1 score, 2 cases （7%, 2/30） reached CC-2 score, and there were statistical significance between the two groups (P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the "rolled carpet" CRS group and the traditional CRS groups (P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion: It is safe and feasible to perform "rolled carpet" CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.

Cross­validation of genes potentially associated with neoadjuvant chemotherapy and platinum­based chemoresistance in epithelial ovarian carcinoma.

Ovarian carcinomas have the poorest prognosis and the highest mortality among gynecological malignancies. Neoadjuvant chemotherapy (NACT) is considered as a novel therapeutic strategy and an alternative treatment for advanced epithelial ovarian cancer (AEOC). The aim of the present study was to identify the core genes related to platinum­based NACT resistance in AEOC and to allow screening at the molecular level for the most appropriate ovarian cancer patients for NACT. We obtained three drug­resistant microarrays GSE114206, GSE41499 and GSE33482 from the Gene Expression Omnibus (GEO) database as well as a microarray representing NACT, GSE109934. Bioinformatics analysis revealed the nature of the four potential candidate genes for using in functional enrichment analyses and interaction network construction. The potential associations and possible genetic alterations among the DEGs were summarized using the STRING database in Cytoscape and the cBioPortal visualization tool, respectively. A total of 63 genes were identified as DEGs from GSE109934 representing NACT. From the drug­resistant GSE114206 and GSE41499 datasets, 106 DEGs containing 36 upregulated genes and 70 downregulated genes were selected, and from the drug­resistant GSE114206 and GSE33482 datasets, 406 DEGs with 157 upregulated genes and 249 downregulated genes were selected. The 36 upregulated DEGs and the 70 downregulated genes were notably abundant in the different categories. In KEGG pathway analysis, the 157 upregulated genes and the 249 downregulated genes were concentrated in distinctive signaling pathways. Four potential genes associated with NACT and platinum­based chemoresistance were screened, including nuclear factor of activated T­cells, cytoplasmic 1 (NAFTc1), Kruppel­like factor 4 (KLF4), nuclear receptor subfamily 4 group A member 3 (NR4A3) and hepatocyte growth factor (HGF). Our study showed that the mRNA expression levels of NAFTc1, NR4A3 and HGF were increased in drug­resistant OC cell lines (all P<0.01), whereas the mRNA expression levels of KLF4 were notably lower in the SKOV3­CDDP and HeyA8­CDDP cell line (all P<0.01) but higher in the A2780­CBP cell line. The NAFTc1, KLF4, NR4A3 and HGF genes may be potential therapeutic targets for NACT and platinum­based chemoresistance factors as well as candidate biomarkers in AEOC. Determination of the expression levels of these four genes in tumor tissues before planning NACT treatment or initial surgery would be beneficial for AEOC patients.

Selenium nanoparticles trigger alterations in ovarian cancer cell biomechanics.

High dose selenium acts as a cytotoxic agent, with potential applications in cancer treatment. However, clinical trials have failed to show any chemotherapeutic value of selenium at safe and tolerated doses (<90 µg/day). To enable the successful exploitation of selenium for cancer treatment, we evaluated inorganic selenium nanoparticles (SeNP), and found them effective in inhibiting ovarian cancer cell growth. In both SKOV-3 and OVCAR-3 ovarian cancer cell types SeNP treatment resulted in significant cytotoxicity. The two cell types displayed contrasting nanomechanical responses to SeNPs, with decreased surface roughness and membrane stiffness, characteristics of OVCAR-3 cell death. In SKOV-3, cell membrane surface roughness and stiffness increased, both properties associated with decreased metastatic potential. The beneficial effects of SeNPs on ovarian cancer cell death appear cell type dependent, and due to their low in vivo toxicity offer an exciting opportunity for future cancer treatment.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

Factors associated with referral and completion of genetic counseling in women with epithelial ovarian cancer.

OBJECTIVE: The National Comprehensive Cancer Network recommends that all women diagnosed with epithelial ovarian cancer undergo genetic testing, as the diagnosis of pathogenic variants may inform cancer survival and impact treatment options. The objective of this study was to assess factors associated with referral to genetic counseling in women with epithelial ovarian cancer. METHODS: A retrospective cohort study identified women with epithelial ovarian cancer from 2012 to 2017 at Massachusetts General Hospital and North Shore Medical Center, a community hospital affiliated with Massachusetts General Hospital. Multivariate logistic regression evaluated how race, age, stage, year of diagnosis, insurance status, family history of breast or ovarian cancer, and language relates to the receipt of genetic counseling. RESULTS: Of the total 276 women included, 73.9% were referred for genetic screening, of which 90.7% attended a genetic counseling visit. Older women were less likely to undergo genetic counseling (age ≥70 years: OR 0.26, 95% CI 0.07-0.94, p=0.04). Women who died within 365 days of initial oncology consult rarely reached a genetic counselor (OR 0.05, 95% CI 0.01-0.24, p<0.001). Women with a family history of breast or ovarian cancer were more likely to undergo counseling (OR 3.27, 95% CI 1.74-6.15, p<0.001). There was no difference in receipt of genetic counseling by race, stage, year of diagnosis, insurance status, or language. CONCLUSION: Older women with epithelial ovarian cancer and those who died within 1 year of initiation of care were less likely to undergo recommended genetic counseling. Race, insurance status, and language were not identified as predictive factors, although we were limited in this assessment by small sample size.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Ovarian Cancer: Evaluation of Side Effects in a Single Institution Cohort.

BACKGROUND/AIM: Peritoneal carcinomatosis is a sign of advanced ovarian cancer. If cytoreductive surgery results in a tumor-free situation with the remaining tumor being less than 0.25 cm, Hyperthermic intraperitoneal chemotherapy (HIPEC) may further improve prognosis. PATIENTS AND METHODS: Patients with ovarian cancer and peritoneal carcinomatosis underwent cytoreductive surgery. In 43 patients with optimal tumor debulking, HIPEC was performed. The peri- and post-operative course was observed. Adverse events were recorded after the Clavien-Dindo classification. RESULTS: The median age of the patients was 56 years, the median peritoneal cancer index (PCI) was 13, and the median operation time was 356 min. There was no postoperative surgery associated death. No adverse events were recorded in 16 (37.2%) of 43 patients, no grade III or IV adverse events were reported for 33 (76.7%) patients, and no grade IV adverse events were reported for 41 (95.3%) patients. Grade III adverse events occured in 19 (44.2%) of the 43 patients. Grade IV adverse events occured in 3 (7.0%) of the 43 patients. CONCLUSION: In ovarian cancer, multiple surgical procedures may be necessary in order to have macroscopically eradicated tumor tissue. The combination with HIPEC, further improves survival of patients with peritoneal carcinomatosis.

LGR4 overexpression is associated with clinical parameters and poor prognosis of serous ovarian cancer.

OBJECTIVE: LGR4 expression in serous ovarian cancer paraffin-embedded tissues and fresh tissues were investigated, and its expression associated with clinicopathological parameters and prognosis in serous ovarian cancer was explored. METHODS: From Dec, 2009 to Jan, 2020, 122 paraffin-embedded serous ovarian cancer patients and 41 paired paratumor tissues who were both diagnosed and operated at the memorial hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were selected in this research, respectively, and all of these tissues were performed by immunohistochemistry (IHC) with a polyclonal antibody for LGR4. Meanwhile, from Aug, 2013 to Mar, 2019, 15 cases of serous ovarian cancer fresh tissues and 15 cases of paratumor fresh tissues who were operated at Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were performed with Quantitative Real-time PCR to detect the mRNA expression of LGR4, respectively. RESULTS: LGR4 expression was much higher both in paraffin-embedded and fresh cancer tissues than that in paratumor tissues, respectively, and its expression was associated with recurrence free survival and overall survival in serous ovarian cancer patients. Moreover, in a multivariate model LGR4 was an indeed independent predictor of poor survival in serous ovarian cancer patients. CONCLUSION: LGR4 is upregulated in serous ovarian cancer, and LGR4 is an indeed useful independent prognostic predictor in serous ovarian cancer, and it may provide important clinical value of serous ovarian cancer.

Long-term multidisciplinary integrative therapy management resulted in favorable outcomes for ovarian cancer during pregnancy: a case report and literature review.

BACKGROUND: Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus's development. CASE PRESENTATION: A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient's anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing. CONCLUSIONS: Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists.

Low expression of KIF7 indicates poor prognosis in epithelial ovarian cancer.

The aim of the present study was to investigate kinesin family member 7 (KIF7) expression in epithelial ovarian cancer tissues (paraffin-embedded tissues and fresh) and to explore its expression, association with clinicopathological parameters and prognostic value in patients with epithelial ovarian cancer. A total of 113 paraffin-embedded tumor tissues of epithelial ovarian cancer patients diagnosed and operated at the memorial hospital of Sun Yat-sen University Between December 2009 and March 2017 and 41 paratumor tissues were collected for the present study and were assessed for KIF7 expression using immunohistochemistry. Furthermore, 22 fresh epithelial ovarian cancer tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and March 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of KIF7. The expression of KIF7 was lower in cancer tissues than in paratumor tissues, and KIF7 expression was associated with recurrence-free survival and overall survival in epithelial ovarian cancer patients. Furthermore, multivariate logistic regression analysis indicated that low KIF7 expression was an independent predictor of poor survival in patients with epithelial ovarian cancer. In conclusion, KIF7 has a tumor suppressor role in epithelial ovarian cancer and is a useful independent prognostic predictor. It may hold important value for the clinical diagnosis and treatment of epithelial ovarian cancer.

Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer.

Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 µg PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTXEtOH-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D = 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer.

Low rate of intraperitoneal port placement in ovarian cancer patients, a population-based assessment.

INTRODUCTION: The National Comprehensive Cancer Network (NCCN) guidelines recommend intraperitoneal chemotherapy in optimally debulked stage III ovarian cancer patients. The objective of this investigation was to determine the rate of intraperitoneal port placement in patients undergoing surgery for ovarian cancer in a national database maintained by the American College of Surgeons. METHOD: We identified ovarian cancer patients in the National Surgical Quality Improvement Program database from 2006 to 2012. Demographics, comorbidities, operative outcomes, and postoperative complications were abstracted. Descriptive analyses were conducted using Wilcoxon rank-sum and Chi square tests, and multivariate regression models were used to analyze pre-operative and post-operative variables associated with intraperitoneal port placement. RESULTS: We identified 2659 ovarian cancer patients who underwent primary surgical management. Of these patients, only 128 (4.8%) had an intraperitoneal port placed at the time of surgery. In multivariable analyses, intraperitoneal ports were associated with body mass index ≤25, disseminated cancer, later portion of the study period (2009-2012), and operative time >200 min. Intraperitoneal port placement was not associated with any difference in surgical site infection, wound disruption, major postoperative complication, readmission within 30 days, or death within 30 days. DISCUSSION: Recent investigation of practice at NCCN institutions between 2003 and 2012 found only 35% of eligible ovarian cancer patients received intraperitoneal chemotherapy. Using intraperitoneal port placement as a surrogate for intraperitoneal chemotherapy administration, our investigation suggests an even lower rate (4.8%) nationally.

Outcomes of secondary cytoreductive surgery for patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Most women with advanced epithelial ovarian cancer develop recurrent disease, despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. In observational studies, secondary cytoreductive surgery has been associated with improved survival; however its use is controversial, because there are concerns that the improved outcomes may reflect selection bias rather than the superiority of secondary surgery. OBJECTIVE: To compare the overall survival of women with platinum-sensitive recurrent ovarian cancer treated at National Cancer Institute-designated cancer centers who receive secondary surgery vs chemotherapy. STUDY DESIGN: This retrospective cohort study included women from 6 National Cancer Institute-designated cancer centers diagnosed with platinum-sensitive recurrent ovarian cancer between January 1, 2004, and December 31, 2011. The primary outcome was overall survival. Propensity score matching was used to compare similar women who received secondary surgery vs chemotherapy. Additional analyses examined how these findings may be influenced by the prevalence of unobserved confounders at the time of recurrence. RESULTS: Among 626 women, 146 (23%) received secondary surgery and 480 (77%) received chemotherapy. In adjusted analyses, patients who received secondary surgery were younger (P = 0.001), had earlier-stage disease at diagnosis (P = 0.002), and had longer disease-free intervals (P < 0.001) compared with those receiving chemotherapy. In the propensity score-matched groups (n = 244 patients), the median overall survival was 54 months in patients who received secondary surgery and 33 months in those treated with chemotherapy (P < 0.001). Among patients who received secondary surgery, 102 (70%) achieved optimal secondary cytoreduction. There were no significant differences in complication rates between the 2 groups. In sensitivity analyses, the survival advantage associated with secondary surgery could be explained by the presence of more multifocal recurrences (if 4.3 times more common), ascites (if 2.7 times more common), or carcinomatosis (if 2.1 times more common) among patients who received chemotherapy instead of secondary surgery. CONCLUSION: Patients with platinum-sensitive recurrent ovarian cancer who received secondary surgery had favorable surgical characteristics and were likely to have minimal residual disease following secondary surgery. These patients had a superior median overall survival compared with patients who received chemotherapy, although unmeasured confounders may explain this observed difference.

Efficacy of hyperthermic intraperitoneal chemotherapy in patients with epithelial ovarian cancer: a meta-analysis.

Objective: The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer (EOC) is still controversial. Present analysis aims to evaluate the survival benefit of HIPEC in treatment of EOC patients. Methods: Articles related to 'HIPEC' and 'ovarian cancer' were comprehensively searched in four databases (PubMed, EMBASE, MEDLINE and Cochrane Library) up to 4 February 2018. Eligible studies were identified depending on the selection criteria. The survival outcome and adverse events were collected. The relationship between HIPEC and survival of EOC was assessed using random-effects models. Results: A total of 1464 patients from 17 trials were subjected to analysis. The pooled results showed that HIPEC significantly improved overall survival (OS, HR = 0.50, 95% CI 0.36-0.69; p = 0.000) and progression-free survival (PFS, HR = 0.57, 95% CI 0.47-0.69; p = 0.000) among EOC patients when compared with no HIPEC controls. Similar results were observed in each year rate of survival. Subgroup analysis didn't lead to the opposite results, except no significant increased 1-year of OS in primary EOC and 1- and 2-year of PFS in recurrent EOC treated with HIPEC were observed. No significant difference existed in the adverse events and mortality between HIPEC and no HIPEC. Conclusions: HIPEC is associated with improved OS and PFS in both primary and recurrent EOC. However, no significant increased 1- and 2-year of PFS were reached in recurrent EOC treated with HIPEC. Further prospective randomized controlled trials are warranted.