Suboptimal Debulking Research Articles

Prediction of optimal debulking surgery in ovarian cancer.

The mainstay management of advanced ovarian cancer is maximal cytoreductive surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) are alternative treatments for patients with comorbidity, poor performance status, and predicted for suboptimal debulking surgery. It is the invariable principle in any situation that no residual disease after the completion of surgery is useful for patients with ovarian cancer. Therefore, the prediction of optimal debulking before the treatment of ovarian cancer is of utmost importance. Many studies have reported on the use of serum biomarkers, such as cancer antigen 125 (CA125) or human epididymis 4 (HE4), and imaging studies, such as computed tomography (CT), diffusion-weighted magnetic resonance imaging (DW-MRI), and positron emission tomography (PET)/CT, to identify adequate surgical candidates for primary debulking surgery (PDS). Laparoscopy has also been studied as a reliable tool for the prediction of optimal debulking. Here, we summarize a review of the related literature.

Cytomegalovirus and systemic inflammation at time of surgery is associated with worse outcomes in serous ovarian cancer

Objectives: Cytomegalovirus (CMV) is a common infection that establishes latency in healthy people. CMV has been associated with alterations of the immune compartment leading to improved responses, while inflammation has been shown to adversely impact outcomes. We investigated whether CMV serostatus predicts outcomes in ovarian cancer in the presence or absence of inflammation.Methods: A total of 106 patients with serous ovarian cancer from 2006 to 2009 were analyzed. CMV and systemic inflammation was measured using CMV immunoglobulin G (IgG) and C-reactive protein (CRP), respectively, in serum collected prior to cytoreduction. Patients were stratified by CMV IgG (non-reactive, reactive/borderline) and CRP (≤10, >10 mg/L) status. Overall survival (OS) and recurrence-free survival (RFS) were compared by group using log-rank tests and Cox proportional hazards regression models adjusting for age at surgery.Results: Of 106 eligible patients, 40 (37.7%) were CMV+/CRP+, 24 (22.6%) CMV+/CRP-, 19 (17.9%) CMV−/CRP+, and 23 (21.7%) CMV−/CRP−. CRP+ had higher CA-125 levels (P = 0.05) and higher rates of suboptimal debulking (P = 0.03). There were no other significant differences in demographic, surgical, or pathologic factors between groups. CMV+/CRP+ patients median RFS and OS were 16.9 months (95% CI: 9.0–21.1) and 31.7 months (95% CI: 25.0–48.7), respectively, with a significantly worse RFS (aHR: 1.85, 95% CI: 1.05–3.24, P = 0.03) and OS (aHR: 2.12, 95% CI: 1.17–3.82, P = 0.01) compared to CMV−/CRP− (RFS = 31.2 months (95% CI: 16.0–56.4) and OS = 63.8 months (95% CI: 50.7–87.0)). CMV+/CRP− group displayed the longest OS (89.3 months).Conclusions: Previous exposure to CMV and high CRP at surgery portended worse RFS and OS compared to women who tested negative. The CMV+/CRP− group had the longest OS, indicating that CMV status alone, in the absence of inflammation, may be protective.

Higher Level of Fatty Acid Synthase Enzyme Predicts Lower Rate of Completing Debulking Surgery in Epithelial Ovarian Cancer.

Background:The most dominant histopathologic type of ovarian cancer is epithelial ovarian cancer (EOC). Primary debulking surgery determines the treatment success and prognosis of advanced stage EOC. To maintain survival and progression, cancer cells need fatty acid synthase enzyme (FASN). The aim of this study was to evaluate preoperative serum FASN and CA 125 as predictors of primary debulking surgery results in patients with EOC. Methods:An observational cross-sectional study was performed on consecutive patients who underwent debulking surgery for suspected ovarian cancer at Dr. Hasan Sadikin Hospital Bandung from 2017 to 2019. Before debulking surgery, blood samples were examined for the serum levels of FASN and CA 125 using ELISA.Results:There were 53 patients enrolled in this study. Compared with the optimal debulking surgery group, the significant suboptimal debulking surgery group had significantly lower mean serum levels of FASN (0.46 ± 0.144 vs. 0.36 ± 0.128, p = 0.012) and CA 125 (964.22 ± 1722.5 vs. 264.98 ± 251.8, p = 0.002). The cutoff value was highest for the combination of FASN and CA 125 [410.06, area under the curve (AUC) = 77.5% (95% CI 65.5% to 81.9%, p = 0.001)] than for FASN alone [0.375, AUC = 71.3% (95% CI 56.8% to 85.8%, p = 0.009)] and CA 125 alone [222.5, AUC = 75.3% (95% CI 62.5% to 88.1%, p =0.002)]. Conclusion:The serum levelof FASN was correlated with suboptimal debulking surgery.

Are Epithelial Ovarian Cancers of the Mesenchymal Subtype Actually Intraperitoneal Metastases to the Ovary?

Primary ovarian high-grade serous carcinoma (HGSC) has been classified into 4 molecular subtypes: Immunoreactive, Proliferative, Differentiated, and Mesenchymal (Mes), of which the Mes subtype (Mes-HGSC) is associated with the worst clinical outcomes. We propose that Mes-HGSC comprise clusters of cancer and associated stromal cells that detached from tumors in the upper abdomen/omentum and disseminated in the peritoneal cavity, including to the ovary. Using comparative analyses of multiple transcriptomic data sets, we provide the following evidence that the phenotype of Mes-HGSC matches the phenotype of tumors in the upper abdomen/omentum: (1) irrespective of the primary ovarian HGSC molecular subtype, matched upper abdominal/omental metastases were typically of the Mes subtype, (2) the Mes subtype was present at the ovarian site only in patients with concurrent upper abdominal/omental metastases and not in those with HGSC confined to the ovary, and (3) ovarian Mes-HGSC had an expression profile characteristic of stromal cells in the upper abdominal/omental metastases. We suggest that ovarian Mes-HGSC signifies advanced intraperitoneal tumor dissemination to the ovary rather than a subtype of primary ovarian HGSC. This is consistent with the presence of upper abdominal/omental disease, suboptimal debulking, and worst survival previously reported in patients with ovarian Mes-HGSC compared to other molecular subtypes.

Extra Gastrointestinal Stromal Tumor Pada Ovarium, Kasus Jarang

Objective : This article objective is to describe a woman with extra gastrointestinal stromal tumor (extra GIST) in ovary; Method : A case report and literature review; The author reports a woman 54 years old with complaints of swelling in the abdomen. Tumors suspected originate from ovary with an extension to abdominal wall. The patient had history of previous ovarian tumor surgery with pathological anatomy diagnosis was thecoma. Working diagnosis of the patient was residif ovarian malignancy and then suboptimal debulking was performed. Microscopically, ovarian tumors appear cellular and diffuse, partially arranged fascicles. Cells with rounded-spindle nuclei, mitosis ≥ 4 per 10 HPF. The conclusion was malignant thecoma which metastasizes to peritoneum and omentum. Differential diagnosis were GIST and leiomyosarcoma. Immunohistochemistry examination was performed with Calretinin and CD117 to rule out the differential diagnosis. Calretinin were negative and CD117 were strongly positively smeared. Based on the morphology and positive CD117 results, diagnosis was extra GIST of ovary.; Conclusion: Extra GIST in the ovary is an unusual location so that it can be misdiagnosed as a gynecological disorder. The differential diagnosis at this location is quite limited including thecoma, fibrothecoma and leiomyosarcoma.Keywords: extra gastrointestinal stromal tumor, ovary, thecoma

Extra Gastrointestinal Stromal Tumor Pada Ovarium, Kasus Jarang

Objective : This article objective is to describe a woman with extra gastrointestinal stromal tumor (extra GIST) in ovary; Method : A case report and literature review; The author reports a woman 54 years old with complaints of swelling in the abdomen. Tumors suspected originate from ovary with an extension to abdominal wall. The patient had history of previous ovarian tumor surgery with pathological anatomy diagnosis was thecoma. Working diagnosis of the patient was residif ovarian malignancy and then suboptimal debulking was performed. Microscopically, ovarian tumors appear cellular and diffuse, partially arranged fascicles. Cells with rounded-spindle nuclei, mitosis ≥ 4 per 10 HPF. The conclusion was malignant thecoma which metastasizes to peritoneum and omentum. Differential diagnosis were GIST and leiomyosarcoma. Immunohistochemistry examination was performed with Calretinin and CD117 to rule out the differential diagnosis. Calretinin were negative and CD117 were strongly positively smeared. Based on the morphology and positive CD117 results, diagnosis was extra GIST of ovary.; Conclusion: Extra GIST in the ovary is an unusual location so that it can be misdiagnosed as a gynecological disorder. The differential diagnosis at this location is quite limited including thecoma, fibrothecoma and leiomyosarcoma.Keywords: extra gastrointestinal stromal tumor, ovary, thecoma

Similar Overall Survival Using Neoadjuvant Chemotherapy or Primary Debulking Surgery in Patients Aged Over 75 Years with High-Grade Ovarian Cancer.

To perform a hypothesis-generating evaluation of patient outcomes following neoadjuvant chemotherapy (NACT) compared with those following primary debulking surgery (PDS) in patients over age 75 with high-grade ovarian cancer. This was a retrospective cohort study of consecutive patients aged 75 years and older, with high-grade ovarian cancer. Data were analyzed in SPSS 25.0 using descriptive statistics to characterize groups based on primary treatment modality, Kaplan-Meier survival curves to estimate overall and progression-free survival, and Cox proportional hazards to analyze confounders. Of 429 patients with stages III and IV high-grade ovarian cancer (endometrioid and serous), 71 were aged older than 75 years and met our criteria for inclusion; 58 were treated with NACT while 13 underwent primary debulking. Sixteen patients did not undergo interval debulking following NACT. There were no significant differences in demographic characteristics between the groups. Following NACT, more patients were completely debulked-36.2% versus 21% (P=0.000)-and had a shorter length of stay (5 vs. 7 d; P=0.018). Overall survival was similar between the NACT and PDS groups (58.7 vs. 59.7 mo; LR -0.836; P=0.361) despite lower progression-free survival in the NACT group (25.9 vs. 47.1 mo; P=0.042; LR 4.31). Both progression-free and overall survival were significantly higher when patients undergoing NACT achieved complete debulking (21.7 and 102.3 mo, respectively) compared with suboptimal debulking (12.03 and 14.2 mo, respectively). In this select group older patients with stage III and IV high-grade ovarian cancers, neoadjuvant chemotherapy may be considered without compromising outcomes and contributes to complete debulking.

Histotype-specific analysis of acid ceramidase expression in ovarian cancer.

Acid ceramidase (ASAH1) is a key player in sphingolipid metabolism and signaling. It has prognostic value for several cancers, but histotype-specific analyses of ovarian cancer are not yet available. We used three retrospective TMA cohorts encompassing a total of 1106 ovarian cancers with follow-up data for immunohistochemical analysis of acid ceramidase (ASAH1) expression. Patients with sub-optimal debulking and persistent residual tumor after surgery introduced bias in the prognostic analysis and were excluded from further studies. Overall, we detected an association of ASAH1 expression with better prognosis in ovarian cancer patients. ASAH1 expression differed between histological ovarian cancer histotypes with most frequent expression in endometrioid and clear cell ovarian cancer, which are both associated with good prognosis. Stratified subgroup analyses within these histotypes did not reveal significant survival differences, but the power of the analysis may be limited by smaller sample sizes. In contrast to breast cancer, we found only a modest concordance between estrogen receptor status and ASAH1 expression within the endometrioid ovarian cancer histotype. In an exploratory analysis of estrogen receptor negative endometrioid ovarian cancer, ASAH1 expression was associated with significantly better overall survival (P = 0.007). Acid ceramidase is most frequently expressed in endometrioid and clear cell histotypes and could add independent prognostic value to estrogen receptor in endometrioid ovarian cancer. Modulating sphingolipid metabolism may lead to novel therapeutic intervention strategies for this disease.

Risk predictors of early recurrence in women with epithelial ovarian cancer in Lagos, Nigeria.

Introductionepithelial ovarian cancer (EOC) is the most lethal gynaecological cancer with a recurrence rate as high as 85% after an initial treatment. However, there are currently no reliable means of predicting the risk of recurrence after first-line treatment. This study investigated the risk factors that predict early recurrence of EOC after primary treatment among women in Lagos, Nigeria.Methodsthis was a retrospective cohort study involving the review of all histologically confirmed EOC patients managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. A study proforma was used to retrieve relevant information and descriptive statistics were computed for all data. The associations between variables were tested and multivariate analysis was done to adjust for all the possible characteristics that predict early EOC recurrence.Resultsthe rate of recurrence of EOC was 76.4%. Suboptimal debulking surgery is the only independent predictor of early tumour recurrence.Conclusionwomen should be adequately counselled and encouraged to report their symptoms early to ensure optimal primary treatment. Strategic efforts should also be made to further improve subspecialty training programs and skills development in gynaecological oncology in Nigeria and sub-Saharan Africa.

Serum calretinin as an independent predictor for platinum resistance and prognosis in ovarian cancer.

Calretinin (CRT) is a calcium-binding protein that controls intracellular calcium signaling. Besides its prominent expression in neurons, serum CRT (sCRT) has recently been suggested as blood-based biomarker for prediagnostic mesothelioma detection. CRT is expressed in ovarian cancer tissues in up to 40% of cases; however, its clinical relevance as blood-based biomarker for ovarian cancer is unknown. sCRT was determined by calretinin enzyme-linked immunoabsorbent assay (Calretinin-ELISA, DLD Diagnostika GmbH, Hamburg, Germany) in a total of 515 serum samples from 116 healthy controls and 134 ovarian cancer patients (thereof 86% with Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] III/IV), including samples at primary diagnosis and at four longitudinal follow-up time points in the course of treatment and at recurrence. sCRT level was significantly increased in ovarian cancer patients compared to healthy controls (estimated difference = 0.3 ng/ml, p < 0.001), was mostly independent from CA125 (r ≤ 0.388) and enabled accurate discrimination between cases and controls (area under the curve = 0.85). Higher sCRT level at primary diagnosis predicted suboptimal debulking (p < 0.001) and was associated with advanced FIGO-stage (p < 0.001) and increased amount of ascites (p < 0.001). sCRT levels at primary diagnosis and its dynamics in the course of chemotherapy were independent predictors for poor progression-free survival (hazard ratio [HR] = 1.99, confidence interval [CI] = [1.13-3.52], p = 0.0181) and overall survival (HR = 15.4, CI = [1.92-124], p = 0.0099). Furthermore, sCRT at primary diagnosis or a relative sCRT increase in the time interval between surgery and the onset of chemotherapy were both independent predictors of platinum resistance (OR = 4.99, CI = [3.50-16,001], p = 0.0016; OR = 2.41, CI = [1.37-6,026], p = 0.0271, respectively). This is the first study that suggests sCRT as liquid biopsy marker for independent prediction of platinum resistance and prognosis.

Cytoreductive surgery in advanced stage malignant ovarian germ cell tumors

IntroductionTo evaluate the survival effect of cytoreductive surgery in advanced stage malignant ovarian germ cell tumors (MOGCT). Material and MethodsClinicopathological data of patients with MOGCT that were treated between 1991 and 2014. Maximal debulking was defined as no gross residual tumor after primary or recurrence surgery; optimal and suboptimal debulking were used for patients with residual tumors of ≤1cm and >1cm, respectively. ResultsIn total, 31 patients with advanced stage MOGCT were analyzed. The median age at diagnosis was 21 (14-57) years. The median follow-up duration was 64.1 months. Of these 31 patients; 7 patients underwent sub-optimal debulking, 5 patients had optimal surgery and 18 had maximal debulking. Five-year DFS according to surgical resection rates were 29% in suboptimal debulking group, 75% in optimal debulking group and 93% in maximal cytoreduction group (p<0.001). Three of seven patients who underwent sub-optimal debulking were died of disease, however no deaths were seen in patients with optimal and maximal debulking. Five-year OS was 32% in suboptimal debulking group, and 100% in optimal and maximal debulking groups (p=0.001). DiscussionThe benefit of cytoreductive surgery is less well-established in MOGCT of ovary compared to ovarian tumors of epithelial origin due to rareness of this histological subtype. Patients with MOGCT are usually younger and preservation of fertility is an important issue which may lead to suboptimal procedures, sometimes in exchange for diminished survival. Our data demonstrated that maximal cytoreduction should be aimed in patients with advanced stage MOGCT, as it is significantly associated with improved overall survival.

Correlation of differential ascites volume with primary cytoreductive surgery outcome, lymph node involvement, and disease recurrence in advanced ovarian cancer.

High-grade serous ovarian cancer accounts for a disproportionate number of deaths from gynecologic malignancies. It typically presents at an advanced stage and with a high volume of ascites a common presenting feature. The aims of this study is to evaluate the association between ascites volume at the time of primary surgery for advanced stage ovarian cancer with surgical outcomes and patterns of recurrence. A retrospective review of stage III/IV high-grade serous ovarian cancer patients who underwent primary surgery at two centers between March 2003 to June 2016. Patients were categorized as low-volume ascites (≤ 200 mL) vs high-volume (≥ 1 L). Patients with an unknown volume of ascites or neoadjuvant chemotherapy were excluded. Patients' characteristics were compared for the two groups. Probability of recurrence over time and the HR from a proportional hazards model for sub-distribution were calculated. A total of 210 patients were included, 90 (42.9%) patients in the low-volume and 120 (57.1%) patients in the high-volume group. Patients in the low-volume group were older with a median age of 60.2 years vs 56.8 years in the high-volume group and had lower serum CA-125 levels (mean 223 vs 971.5 U/mL). The low-volume group had better surgical outcome with suboptimal debulking (> 1 cm residual disease) in only 17.8 % vs 39.2 % in the high-volume group and had longer median time to recurrence (2.8 years in low-volume vs 1.6 years high-volume group). At the time of recurrence, the low-volume group had a less disseminated pattern of recurrence, lower rates of ascites (20 % in the low-volume group vs 37.2 % in the high-volume group), and a trend toward lower serum CA125 levels (mean 352.8 vs 596.9 U/mL). Advanced stage serous ovarian cancer patients who present with low-volume ascites have lower serum CA125 levels, more optimal cytoreduction rates, and longer disease-free interval. The low-volume group had less ascites, less disseminated disease, and a trend toward lower serum CA125 levels at the time of recurrence.

Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p &lt; 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p &lt; 0.001) and were associated with advanced FIGO-stage (p &lt; 0.001) and high volume of ascites (p &lt; 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

Maximal cytoreduction is related to improved disease-free survival in low-grade ovarian serous carcinoma.

To evaluate the factors predicting oncologic outcomes in low-grade ovarian serous carcinoma (LGOSC). Seventy patients with LGOSC were included in the study. According to the residual disease present at the end of the initial cytoreductive surgery (CRS), surgical outcomes are defined as follows: maximal CRS for absence of macroscopic residual tumors, optimal CRS for macroscopic residual tumors with diameters ranging from 0.1 to ⩽1 cm diameter, and suboptimal CRS for macroscopic residual tumors measuring >1 cm in diameter. Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were 61% and 83%, respectively. Surgical outcomes were suboptimal in 3 (4.3%) patients, optimal in 8 (11.4%) patients, and maximal in 59 (84.3%) patients. Stage and surgical outcomes were related to DFS (p < 0.05). Compared with maximal CRS, the presence of residual tumors (suboptimal and optimal debulking) was related to threefold increased risk of disease failure (recurrence or progression) (hazard ratio [95% confidence interval] 3.00 [1.27-7.09]; P=0.012). CSS was associated with disease stage alone (P=0.03). Advanced stage was related with lower DFS and CSS. Maximal CRS facilitates an improvement in DFS. Achieving no residual disease after the completion of surgery should be a cornerstone of LGOSC management.

Laparoscopy for diagnosing resectability of disease in women with advanced ovarian cancer.

This is an update of a Cochrane Review that was originally published in 2014, Issue 2.The presence of residual disease after primary debulking surgery is a highly significant prognostic factor in women with advanced ovarian cancer. In up to 60% of women, residual tumour of > 1 cm is left behind after primary debulking surgery (defined as suboptimal debulking). These women might have benefited from neoadjuvant chemotherapy (NACT) prior to interval debulking surgery instead of primary debulking surgery followed by chemotherapy. It is therefore important to select accurately those women who would best be treated with primary debulking surgery followed by chemotherapy from those who would benefit from NACT prior to surgery. To determine if performing a laparoscopy, in addition to conventional diagnostic work-up, in women suspected of advanced ovarian cancer is accurate in predicting the resectability of disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE via Ovid, Embase via Ovid, MEDION and Science Citation Index and Conference Proceedings Citation Index (ISI Web of Science) to July 2018. We also checked references of identified primary studies and review articles. We included studies that evaluated the diagnostic accuracy of laparoscopy to determine the resectability of disease in women who are suspected of advanced ovarian cancer and planned to receive primary debulking surgery. Pairs of review authors independently assessed the quality of included studies using QUADAS-2 and extracted data on study and participant characteristics, index test, target condition and reference standard. We extracted data for two-by-two tables and summarised these graphically. We calculated sensitivity and specificity and negative predictive values. We included 18 studies, reporting on 14 cohorts of women (including 1563 participants), of which one was a randomised controlled trial (RCT). Laparoscopic assessment suggested that disease was suitable for optimal debulking surgery (no macroscopic residual disease or residual disease < 1 cm (negative predictive values)) in 54% to 96% of women who had macroscopic complete debulking surgery (no visible disease at end of laparotomy) and in 69% to 100% of women who had optimal debulking surgery (residual tumour < 1 cm at end of laparotomy).Only two studies avoided partial verification bias by operating on all women independent of laparoscopic findings, and provided data to calculate sensitivity and specificity. These two studies had no false positive laparoscopies (i.e. no women had a laparoscopy indicating unresectable disease and then went on to have optimal debulking surgery (no disease > 1 cm remaining)).Due to the large heterogeneity pooling of the data was not possible for meta-analysis. Laparoscopy may be a useful tool to identify those women who have unresectable disease, as no women were inappropriately unexplored. However, some women had suboptimal primary debulking surgery, despite laparoscopy predicting optimal debulking and data are at high risk of verification bias as only two studies performed the reference standard (debulking laparotomy) in test (laparoscopy)-positive women. Using a prediction model does not increase the sensitivity and will result in more unnecessarily explored women, due to a lower specificity.

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer.

Nearly one-third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial treatment with platinum-based therapy. Genomic and clinical characterization of these patients may lead to potential alternative therapies. Here, the objective is to classify non-responders into subsets using clinical and molecular features. Using patients from The Cancer Genome Atlas (TCGA) dataset with platinum-resistant or platinum-refractory HGSC, we performed a genome-wide unsupervised cluster analysis that integrated clinical data, gene copy number variations, gene somatic mutations, and DNA promoter methylation. Pathway enrichment analysis was performed for each cluster to identify the targetable processes. Following the unsupervised cluster analysis, three distinct clusters of non-responders emerged. Cluster 1 had overrepresentation of the stage IV disease and suboptimal debulking, under-expression of miRNAs and mRNAs, hypomethylated DNA, “loss of function” TP53 mutations, and the overexpression of genes in the PDGFR pathway. Cluster 2 had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the HIF-1 signaling pathway. Cluster 3 had more optimally cytoreduced stage III patients, overexpression of miRNAs, mixed methylation patterns, and “gain of function” TP53 mutations. However, the survival for all clusters was similar. Integration of genomic and clinical data from patients that do not respond to chemotherapy has identified different subgroups or clusters. Pathway analysis further identified the potential alternative therapeutic targets for each cluster.

Clinico-Epidemiological Study of Epithelial Ovarian Cancer Mansoura Experience

Background & objective: Ovarian cancer is the fifth most common cancer affecting women today. The aim of this retrospective study was to present the epidemiological, pathological, clinical characteristics of epithelial ovarian cancer patients treated at Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospitals in the period between January 2009 and December 2013, with evaluation of progression free survival (PFS) overall survival (OS) and prognostic factors. Patients & methods: This is a retrospective study of epithelial ovarian carcinoma women treated at Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospitals (in the period between January 2009 and December 2013). Data were analyzed after being collected from the patients' medical records. Clinical abstract sheets for all cases were designed. Results: The median age was 55 years (19 – 80 years), 58 patients (39.2%) were ECOG performance status (PS) 1, whereas, 50 patients (33.8%) were PS 0 at presentation. Ninety five patients (64.2%) were postmenopausal at presentation, serous cystadenocarcinoma was the predominant histopathologic type found in 94 patients (63.5%), followed by Endometrioid type (17.5%), 79 patients (53.4%) had stage III disease and 33 patients (22.3%) had stage IV disease. The majority of patients (99 patients 66.9%) had grade III tumors, 140 patients (94.6%) in the study underwent surgical treatment, optimal debulking was done in 85 patients (60.7%), while, suboptimal debulking was done in 55 patients (39.3%), the median overall survival was 49 months, while the median progression free survival was 18 months. Conclusion: the median age was 55 years old, serous carcinoma was the predominant histopathological type. Stage III and IV predominated. Most patients underwent initially surgery followed by adjuvant chemotherapy. The median overall survival & PFS were 49 & 18 months, respectively. Age, tumor histopathology, stage, grade and tumor residue after debulking surgery were significant independent prognostic factors for epithelial ovarian cancer.

The road to long-term survival: Surgical approach and longitudinal treatments of long-term survivors of advanced-stage serous ovarian cancer

ObjectiveIt is unclear if the types of surgical procedures performed on long-term survivors (LTS) of high-grade serous ovarian carcinoma (HGSOC) contribute to prolonged survival. In this case-control study we review the surgical procedures performed on LTS and describe their individual longitudinal disease courses. MethodsWomen with FIGO stage III–IV high-grade serous cancer of the ovary, fallopian tube or peritoneum were selected from the University of Chicago ovarian cancer database. LTS were those surviving >7 years and controls were short-term survivors (STS) living 1–2 years. Patients with non-serous histology, low grade, and low malignant potential tumors were excluded. ResultsWe identified 450 women with stage III/IV HGSOC including 45 LTS and 78 STS. LTS showed a trend towards lower disease burden, yet underwent more aggressive surgical treatment. Interestingly, only 15 LTS (34%) were debulked to microscopic disease and 9 LTS (21%) underwent suboptimal debulking. Two LTS (5%) recurred within 12 months. LTS had heterogeneous clinical courses with 13 (29%) never experiencing a recurrence with 143 months median follow-up and 32 (71%) experiencing a recurrence with 115 months median follow-up. Of the women who recurred, 19 (59%) underwent at least one surgery for recurrence. ConclusionsAggressive surgical treatment intended to achieve microscopic disease, primary debulking surgery, preservation of sensitivity to chemotherapy, and recurrence amenable to secondary debulking are associated with long-term survival. However, clinicopathologic data are insufficient to predict long-term survival of HGSOC. Biologic characterization of these patient's tumors likely holds the key to understanding their unusually favorable courses.

Peri-operative allogeneic blood transfusion is associated with poor overall survival in advanced epithelial ovarian Cancer; potential impact of patient blood management on Cancer outcomes

BackgroundTransfusion related immune modulation associated with red blood cell (RBC) transfusion is thought to result in decreased cancer survival. Results in epithelial ovarian cancer (EOC) have been mixed however most suggest worse oncologic outcomes in patients who were transfused at the time of debulking surgery. The impact of restrictive transfusion strategies on this patient population is currently not known. MethodsWe conducted a retrospective study of women with EOC. The study population was divided into two groups based on whether they were transfused RBCs during the peri-operative period or not. Clinical characteristics and prognosticators were compared between groups. Overall survival was compared between groups based on transfusion status and other known prognostic factors. Cox proportional hazard modeling was used to examine the association between the prognostic factors and the study endpoint. ResultsSixty-six percent of women were transfused. Transfusion was associated with CA125, the use of neoadjuvant chemotherapy (NACT), surgical blood loss, and anemia. The mean pre-transfusion Hgb was 7.8 + 0.6 g/dL and 94% had a hemoglobin level greater than the transfusion threshold of 7 g/dL. RBC transfusion, suboptimal debulking, anemia, and NACT were associated with decreased survival. Only RBC transfusion and suboptimal debulking status remained significant in a multivariate model. ConclusionsPeri-operative RBC transfusion compromises survival in ovarian cancer supporting the need to minimize the use of transfusion at the time of debulking surgery. Adherence to evidence-based transfusion guidelines offers an opportunity to reduce transfusion rates in this population with a resulting positive influence on survival.

Outcome of Bowel Resection in Women with Advanced Ovarian Carcinoma.

To evaluate the mortality and morbidity related to bowel resection in women with advanced ovarian carcinoma. Retrospective case series of 47 women with stage III and IV carcinoma ovary who underwent bowel resection, over the period of 5years from Jan 2011 to Dec 2015. The risk factors for perioperative morbidity and death were determined by regression analysis. The disease free and overall survival were determined by Kaplan-Meier plots. In this cohort, 64% (30/47) had primary debulking, 21% (10/47) had interval debulking, and 15% (7/47) had secondary debulking. The mean period of follow-up was 23months (1 to 45months). There were no anastomotic leaks. The commonest morbidities were relaparotomy (8.5%), surgical site infection (12%), and paralytic ileus (19%). The overall morbidity was 42.6% (20/47). The 30-day mortality was 4.2% (2/47). The recurrence rate was 51% (20/47). The overall mortality from ovarian cancer in this cohort was 40% (19/47) during the follow-up period. Stage and histology seemed to be important risk factors for morbidity. Low BMI and sub-optimal debulking were significant risk factors for recurrence and death in univariate analysis. Bowel resection, in optimally selected cases of advanced carcinoma ovary, is often required for optimal cytoreduction. It carries a reasonable peri-operative mortality and morbidity and improves overall survival.