Suboptimal Cytoreduction Research Articles

Predictive significance of preoperative CT findings for suboptimal cytoreduction in advanced ovarian cancer: a meta-analysis.

BackgroundComputed tomography (CT) has been extensively used in predicting suboptimal cytoreduction (SCR) in advanced ovarian cancer (OC). However, disagreements remain in literatures on the predictive value of CT findings for SCR. This meta-analysis was designed to determine the ability of eight preoperative CT findings to predict SCR in advanced OC.Materials and methodsA comprehensive literature search was conducted for eligible studies to identify the association between the eight preoperative CT findings and SCR in advanced OC. The predictive performances of preoperative CT findings were expressed in terms of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) with pooled proportion.ResultsA total of 10 studies and 1,614 patients were included in this meta-analysis. Large volume ascites had the highest sensitivity (64%, CI 56–71%), with a PLR of 1.3 (CI 1.1–1.5) and an NLR of 0.73 (0.59–0.90), while lymph node involvement had the highest specificity (89%, CI 79–94%). The highest DOR of 3 (CI 2–4) was achieved in peritoneal involvement and large bowel mesentery involvement. The other CT findings had poorer predictive performance.ConclusionPreoperative CT findings have a poor discriminative capacity to predict SCR in advanced OC. Preoperative CT predictors should be used with caution amid clinical decision-making.

Preoperative predictors that impact the survival and outcome of patients undergoing secondary cytoreduction for ovarian cancer

This study aimed to examine the factors affecting feasibility of optimal and complete secondary cytoreductive surgery (SCRS) and to characterise the prognostic factors that correlate with improved survival in patients who underwent SCRS. This is a retrospective single-institutional cohort study of patients who underwent SCRS for recurrent epithelial ovarian cancer (EOC). One hundred and forty-eight patients met inclusion criteria. Platinum sensitivity was associated with complete cytoreduction at SCRS. Factors associated with suboptimal cytoreduction (SOC) were age >55 years, serous histology, largest tumour implant size >4 cm, and SOC at primary surgery. Overall survival analysis showed significantly longer survival with complete cytoreduction compared to optimal and SOC. Surgical outcome of SCRS was an independent predictor of survival regardless of the outcome of primary cytoreduction. Location of the largest implant, DFI and timing of chemotherapy also impact on survival.

Fully sialylated alpha-chain of complement 4-binding protein (A2160): a novel prognostic marker for epithelial ovarian carcinoma.

Fully sialylated alpha-chain of complement 4-binding protein (A2160) is a member of the glycoprotein family and has recently been identified as a diagnostic biomarker for epithelial ovarian cancer. This study examined the utility of A2160 as a prognostic biomarker for this disease. This is a retrospective analysis of prospectively collected plasma samples from 93 women with stage I-IV epithelial ovarian cancer who underwent primary cytoreductive surgery between 2009 and 2014. Pretreatment A2160 levels were correlated to clinico-pathological factors and survival outcome. Women with advanced-stage disease had significantly higher 2160 levels compared to those with early stage disease (stage I-II versus III-IV, median 2.17-2.70 versus 5.31-8.70U/mL, P<0.01). Women with high-grade serous ovarian carcinoma had higher A2160 levels compared to other histologies (6.60 versus 3.01U/mL, P=0.05). Women who had suboptimal cytoreduction had significantly higher A2160 levels than those who achieved optimal/complete cytoreduction (7.02 versus 2.30-3.17U/mL, P<0.01). On univariable analysis, higher A2160 levels were significantly associated with decreased progression-free survival (64-100 versus 1-33%ile, 5-year rates 53.4 versus 78.9%, P=0.029). After controlling for age, CA-125 level, cytoreductive status, histology, and stage, higher A2160 levels remained an independent prognostic factor for decreased progression-free survival (adjusted-hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.01-6.11, P=0.049). Similarly, higher A2160 levels were independently associated with decreased cause-specific survival on multivariable analysis (adjusted-HR 3.07, 95% CI 1.19-7.93, P=0.021). Our study suggests that A2160 may be a useful prognostic biomarker for epithelial ovarian cancer, and higher pretreatment levels of A2160 predicts poor survival outcome.

Peritoneal cancer index as a predictor of survival in advanced stage serous epithelial ovarian cancer: a prospective study.

ObjectiveA numerical score, the peritoneal cancer index (PCI), was developed to reflect the extent of tumor growth in gastric and colorectal cancers and to tailor treatment. This study aimed to examine the value of the PCI score in advanced epithelial ovarian cancer (EOC) regarding completeness of surgical cytoreduction and survival.MethodsThis was a prospective observational cohort study. Patients with primary serous EOC at International Federation of Gynecology and Obstetrics (FIGO) stages IIIB or higher were included. Patients with FIGO stage IVB as well as those assigned to receive neoadjuvant treatment were excluded from the study. The PCI was obtained and registered intraoperatively.ResultsIn the study period we recruited 96 patients with serous EOC stage IIIB–IVA. A PCI score cut-off value of 13 was calculated using a receiver operator characteristic (ROC) curve, above which worse survival is expected (area under the curve [AUC]=0.641; 95% confidence interval [CI]=0.517–0.765; sensitivity and specificity 80.6%, 45.0%, respectively; p=0.050). A multivariate analysis determined that suboptimal surgical cytoreduction was the only independent predictive factor for recurrence (odds ratio [OR]=7.548; 95% CI=1.473–38.675; p=0.015). A multivariate analysis determined that only suboptimal surgical cytoreduction (hazard ratio [HR]=2.33; 95% CI=0.616–8.795; p=0.005), but not PCI score >13 (HR=1.289; 95% CI=0.329–5.046; p=0.716), was an independent predictive factor for death.ConclusionWe conclude from this study that the PCI score is a reliable tool helping to assess the extent of disease in advanced serous EOC patients and may help predicting complete surgical cytoreduction but cannot qualify as a predictor of survival.

Model for Prediction of Optimal Debulking of Epithelial Ovarian Cancer

Background:Primary cytoreduction surgery followed by chemotherapy is the cornerstone treatment for epithelial ovarian cancer (EOC). In patients with a low probability of optimal primary surgical debulking, neoadjuvant chemotherapy (NACT) followed by interval debulking increases the chance of optimal surgery. The aim of this study was to develop a model to identify preoperative predictors for suboptimal cytoreduction.Methods:Medical records of patients with EOC who underwent primary cytoreductive surgery in a referral tertiary gyneco-oncology center were reviewed from 2007 to 2017. Data were collected on a range of characteristics including demographic features, comorbidities, serum tumor markers, hematologic markers, preoperative imaging, surgical procedures, and pathologic reports. Univariate and multivariate analyses were performed to clarify the ability of preoperative factors to predict suboptimal primary surgery.Results:The majority of patients (71.3%) who underwent primary cytoreductive surgery were optimally debulked. Based on the Youden index, the best cut-off point for the serum CA125 level to distinguish suboptimal debulking was 420U/ml with 0.730 (95%CI:0.559 to 0.862) sensitivity and 0.783 (0.684 to 0.862) specificity. Multiple logistic regression results showed that serum CA125 level >420 U/ ml (p value <0.001), the presence of liver metastasis on preoperative imaging (p value: 0.041) and ascites (p value: 0.032) or massive ascites (p value:0.010) significantly increased the risk of suboptimal debulking (logit p = 2.36 CA125 level +1.85 Liverinvolvement +1.68 presence of Ascites+ 2.28 Massive Ascites).Conclusion:The present study suggests that a serum CA125 level >420 U/ml, the presence of ascites or massive ascites and liver metastasis are strong predictors of suboptimal primary surgery in cases of EOC. Based on the constructed model, with any of these 4 factors, the probability of suboptimal debulking in EOC is more than 80%.

Prognostic Factors in Patients Undergoing Primary Cytoreductive Surgery for FIGO Stage IIIC Ovarian, Tubal or Peritoneal Cancer.

The aim of the study is to investigate factors related to overall survival in advanced stage ovarian, tubal, or peritoneal cancer and to identify strong and weak prognostic factors. We retrospectively reviewed 190 patients who underwent primary cytoreductive surgery between 2003 and 2013. Median overall survival duration was founded 58 months (95% CI 49-67). Five-year overall survival ratio was 48.5%. Presence of tumour at upper abdomen, suboptimal cytoreduction (residual >1 cm), surgery without lymphadenectomy, and presence of peritoneal ascites more than 1 L had a significantly negative effect on overall survival, but not histological grade and CA-125 level, by univariate Cox analysis. Age and presence of tumour in the upper abdomen were independent poor prognostic factors according to multivariate Cox model (HR 1.025; 95% CI 1.009-1.040 and HR 1.533; 95% CI 1.039-2.263, respectively). This study supports that the presence of tumour in the upper abdomen is the most important independent poor prognostic factor in patients with performed primary surgery for advanced stage ovarian, tubal, and peritoneal cancer. Upper abdominal metastasis is the most important predictive factor for optimal cytoreduction (P <0.001, HR 6.567; 95% CI 3.059-14.096).

Sub-optimal primary surgery leads to unfavorable immunological changes in ovarian cancer patients

Primary cytoreduction, followed by chemotherapy, is a standard treatment of patients with epithelial ovarian cancer (EOC). However, the effectiveness of this treatment depend on various elements e.g. type of operation. It is accepted that optimal surgery correlates with longer survival of patients. The other element, an efficiency of immune system after surgical intervention although important is less elucidated. The aim of this study was to establish the impact of optimal and sub-optimal operation on immunological status of EOC patients regarding also their overall survival (OS). On the day of primary cytoreduction and 7days after, the selected serum immunological parameters were determined in 49 patients with confirmed EOC. We found that, the level of immunosuppressive (interleukin 10; transforming growth factor-β − TGF-β1) and pro-inflammatory (interleukin-6 and 8) cytokines was significantly higher in the group of patients with advanced stage of disease, compared to early stage. However, the number of circulating CD3+, CD4+ or CD8+ cells, CD19+ and NK cells was similar in both group of EOC patients. The overall survival of patients who underwent optimal cytoreduction was significantly higher than that in whom only sub-optimal surgery was performed. Sub-optimal cytoreduction only partially weakened the serum level of TGF-β1 and IL-8 and what is more enhanced the number of circulating CD4+CD25+high cells in patients with advanced stage of disease. Sub-optimal surgery and high post-operative level of TGF-β1 increased the hazard ratio for patients. Besides, we noticed that the high pre-operative concentration of TGF-β1 could distinguish all EOC patients (independently of FIGO classification) for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking resulted in higher immunosuppression and lower OS of EOC patients.

Associations between residual disease and survival in epithelial ovarian cancer by histologic type.

Surgical cytoreduction has been postulated to affect survival by increasing the efficacy of chemotherapy in ovarian cancer. We hypothesized that women with high-grade serous ovarian cancer, which usually responds to chemotherapy, would derive greater benefit from complete cytoreduction than those with histologic subtypes that are less responsive to chemotherapy, such as mucinous and clear cell carcinoma. We conducted a retrospective cohort study of patients who underwent primary cytoreductive surgery and adjuvant chemotherapy for stage IIIC or IV epithelial ovarian cancer from 2011 to 2013 using data from the National Cancer Database. We constructed multivariable models to quantify the magnitude of associations between residual disease status (no residual disease, ≤1cm, or >1cm) and all-cause mortality by histologic type among women with clear cell, mucinous, and high-grade serous ovarian cancer. Because 26% of the sample had unknown residual disease status, we used multiple imputations in the primary analysis. We identified 6,013 women with stage IIIC and IV high-grade serous, 307 with clear cell, and 140 with mucinous histology. The association between residual disease status and mortality hazard did not differ significantly among histologic subtypes of ovarian cancer (p for interaction=0.32). In covariate adjusted models, compared to suboptimal cytoreduction, cytoreduction to no gross disease was associated with a hazard reduction of 42% in high-grade serous carcinoma (hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.49-0.68), 61% in clear cell carcinoma (HR=0.39, 95% CI=0.22-0.69), and 54% in mucinous carcinoma (HR=0.46, 95% CI=0.22-0.99). We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy.

Laparoscopic-based score assessment combined with a multiple disciplinary team in management of recurrent ovarian cancer: A single-center prospective study for personalized surgical therapy.

The aim of the study was to evaluate the effect of laparoscopic-based score combined with a multiple disciplinary team (MDT) for predicting optimal cytoreduction and perform personalized surgical treatment in recurrent ovarian cancer (ROC).The study is a single-center, prospective investigation. From March 2013 to May 2015, the consecutive treated patients with platinum-sensitive ROC were collected in Yangpu Hospital. The appropriated patients were enrolled into the study to perform the laparoscopic-based PIV (predictive index value) score assessment with an MDT for predicting optimal cytoreduction. The PIV cutoff value was confirmed to be 8. Patients of PIV <8 received laparoscopic/laparotomy secondary surgery following chemotherapy, and the ones with PIV ≥8 did chemotherapy alone. Sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and overall accuracy for each range of PIV score were calculated. All recruited patients participated in follow-up observation. Overall survival was recorded.In total, 58 eligible ROC patients received laparoscopy assessment. Forty-one patients of PIV <8 received secondary cytoreductive surgeries. Twenty-three (23/41 56.1%) attained optimal cytoreduction. However, 8 of 23 achieved completed cytoreduction. Also, 17 patients of PIV ≥8 underwent chemotherapy alone. Sensitivity, specificity, PPV, NPV, and overall accuracy for PIV ≥8 were 60%, 100%, 100%, 25%, and 64.7%, respectively. Overall survival in patients performing optimal cytoreduction was significantly higher than in those undergoing suboptimal cytoreduction or chemotherapy alone (45.9 ± 2.5 vs 36.7 ± 4.3 months, P = .047; 45.9 ± 2.5 vs 35.8 ± 3.4 months, P = .027).Laparoscopic-based score assessment plus MDT helps to identify the appropriate patients to perform optimal secondary cytoreduction and provide a personalized surgical approach in management of ROC.

Concerning CT features used to select patients for treatment of peritoneal metastases, a pictoral essay

Background: During the Fifth International Workshop on Peritoneal Surface Malignancy in Milan in 2008, a consensus was reached that contrast-enhanced CT (ceCT) was the principal imaging modality for patients being evaluated for treatment of peritoneal metastases. This fact being accepted, the radiologic criteria for that may exclude patients from a high value cytoreductive surgery (CRS) plus hyperthermic perioperative chemotherapy (HIPEC) have not been reliably determined.Methods: From a consensus of surgeons and radiologists, radiologic images were selected and their determinant radiologic characteristics described. The anatomic pathology causing the abnormal images were identified and characterised. The cytoreductive surgical procedures that may, in selected patients, result in a complete resection of the pathology identified were presented.Results: Radiographs of 15 CT images that cause concern when a patient is being evaluated for CRS were listed. The anatomic pathology these images define and possible surgical resections they require were reviewed. The surgical implications of the absence or presence of a single, or of multiple concerning CT features was extracted from the surgical and radiologic literature.Conclusions: There is a definite need to identify new pre-operative imaging parameters to define optimal indication of CRS with HIPEC. The presence of a single concerning radiologic feature is associated with the possibility of an adverse outcome or technically more complex resections associated with increased morbidity and mortality. If two or more of the concerning radiologic features are described from the CT, suboptimal cytoreduction will usually occur.

Interval robotic cytoreduction following neoadjuvant chemotherapy in advanced ovarian cancer.

The objective of this study is to review our experience with robotic interval cytoreduction following neoadjuvant chemotherapy for advanced ovarian cancer. We retrospectively reviewed patients with advanced ovarian cancer treated with neoadjuvant chemotherapy (NAC) and interval robotic cytoreduction (IRC) between 2011 and 2016 at the University of Rochester Medical Center. Demographic information, chemotherapy treatment, operative results, and follow-up were extracted from medical records. Twenty-nine patients underwent IRC after a mean of 3.9 cycles of NAC. The mean operative time was 165min with a mean EBL of 107cc. The mean length of stay was 2.0days. One case (3.3%) was converted to an open procedure because of extensive tumor not amenable to robotic cytoreduction. Overall, 19 (66%) patients underwent an R0 cytoreduction, 8 (28%) an optimal (<1cm) cytoreduction, and 2 (7%) a suboptimal cytoreduction. The median overall survival was 39.7months and median progression-free survival was 21.2months. Interval robotic cytoreduction following NAC is feasible and may be preferable to open interval cytoreductive surgery, in specific patients, to minimize morbidity and length of hospital stay.

Abstract NTOC-113: TGF–β SIGNALING INHIBITION AS A POTENTIAL APPROACH TO TARGET SUBOPTIMALLY DEBULKED OVARIAN TUMORS

Abstract The current standard of care for all patients with high-grade, advanced-stage serous ovarian cancer is surgery followed by adjuvant chemotherapy. Resection of all visible residual disease to less than 1 cm is associated with a favorable prognosis, but this optimal debulking can only be achieved in ~70% of patients. Patients with suboptimal cytoreduction are presumed to have lower response rates to subsequent chemotherapy and are known to have a poor prognosis. Recently, we performed a meta-analysis of 1,525 publicly available expression profiling assays and identified a 200-gene expression signature of primary ovarian tumors to predict the outcome of debulking surgery. The signature was validated using two independent sets of tumors. This debulking signature consists of transcripts positively regulated by TGF-β, indicating that hyperactivation of TGF-β signaling may be responsible of the aggressive biological and clinical behavior of suboptimally debulked tumors. In this study, we evaluated the potential anti-tumor effect of TGF-β signaling blockade in ovarian cancer cells in vitro and in vivo. Integrated TGF-β signaling was observed in 8 of 10 ovarian cancer cell lines tested by a SMAD-binding element based luciferase assay. The potential anti-tumor effect of a small molecular TGFBR1 kinase inhibitor LY2157299 was further investigated in SKOV3 cell line, which presents both endogenous and inducible TGF-β signaling and is highly disseminative when inoculated into immunodeficient mice. Although imposing minimal effect on in vitro cellular proliferation, LY2157299 significantly inhibited tumor-dissemination related biological processes in SKOV3 cells including migration, invasion and mesothelial cell adhesion. In an interperitoneal SKOV3 xenograft model, administration of LY2157299 significantly increased cisplatin related cytotoxicity and tumor burden reduction. Taken together, our study has provided evidence for the potential clinical use of LY2157299 to improve the treatment and survival of women with suboptimal surgery. Citation Format: Wei Wei and Michael J. Birrer. TGF–β SIGNALING INHIBITION AS A POTENTIAL APPROACH TO TARGET SUBOPTIMALLY DEBULKED OVARIAN TUMORS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-113.

A multicenter assessment of the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease at primary debulking for advanced epithelial ovarian cancer

ObjectiveTo assess the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease (RD) at primary cytoreduction in advanced ovarian cancer. MethodsA prospective, non-randomized, multicenter trial of patients who underwent primary debulking for stage III–IV epithelial ovarian cancer previously identified 9 criteria associated with suboptimal (>1cm residual) cytoreduction. This is a secondary post-hoc analysis looking at the ability to predict any RD. Four clinical and 18 radiologic criteria were assessed, and a multivariate model predictive of RD was developed. ResultsFrom 7/2001–12/2012, 350 patients met eligibility criteria. The complete gross resection rate was 33%. On multivariate analysis, 3 clinical and 8 radiologic criteria were significantly associated with the presence of any RD: age≥60years (OR=1.5); CA-125≥600U/mL (OR=1.3); ASA 3–4 (OR=1.6); lesions in the root of the superior mesenteric artery (OR=4.1), splenic hilum/ligaments (OR=1.4), lesser sac >1cm (OR=2.2), gastrohepatic ligament/porta hepatis (OR=1.4), gallbladder fossa/intersegmental fissure (OR=2); suprarenal retroperitoneal lymph nodes (OR=1.3); small bowel adhesions/thickening (OR=1.1); and moderate-severe ascites (OR=2.2). All ORs were significant with p<0.01. A ‘predictive score’ was assigned to each criterion based on its multivariate OR, and the rate of having any RD for patients who had a total score of 0–2, 3–5, 6–8, and ≥9 was 45%, 68%, 87%, and 96%, respectively. ConclusionsWe identified 11 criteria associated with RD, and developed a predictive model in which the rate of having any RD was directly proportional to a predictive score. This model may be helpful in treatment planning.

Correlation of Pattern of Spread and Outcomes in Advanced Epithelial Ovarian Cancers.

The purpose of this study was to correlate the pattern of spread with oncological outcomes in advanced ovarian cancer patients. This is a retrospective analysis of 55 consecutive patients who had advanced epithelial ovarian cancer or primary peritoneal carcinomatosis (stages 3C and 4) with primary surgical intervention as the initial modality of treatment. Based on the spread of disease, they were further classified into class A: disease confined to the pelvis (excluded); class B: disease extending to the lower abdomen and omentum; class C: diffuse small-bowel disease with or without A, B, or D; and class D: disease in the upper abdomen. There were 17 patients (30.9%) in class B, 17 (30.9%) in class C, and 21 (38.2%) in class D. The number of patients with suboptimal cytoreduction was highest in class C (six patients). At the end of follow-up (median 38.6months), 16 patients had no evidence of disease and 26 patients were alive with disease. The 3-year overall survival rates in classes B, C, and D were 94.1, 52.5, and 93.3%, respectively. The 3-year progression-free survival rates were 55.8, 11.8, and 41.9%, respectively. The rates were lowest for class C. The differences in the overall survival rate (p<0.001) and progression-free survival rate (p=0.001) were statistically significant. In advanced ovarian cancer patients, the presence of disease in the small-bowel serosa and mesentery results in poorer outcomes in terms of overall and progression-free survival. The number of patients with suboptimal cytoreduction was also highest in this group.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions

ObjectiveTo determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. Materials and MethodsA retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. ResultsIn total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28–63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. ConclusionClinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment.

Correlation between cytoreduction outcome and staging of ovarian cancer with preoperative blood cell count

Objective To investigate the relationship between cytoreduction outcome and staging of ovarian cancer with preoperative blood cell count. Methods The data of 148 ovarian cancer patients from January 2007 to June 2012 were analyzed retrospectively. Clinicopathological and blood cell count data were collected, and benign ovarian tumor group (n=96) as controls. Results Compared to the control group, there were significant differences in the number of white blood cells, neutrophils, lymphocytes, monocytes, platelets, neutrophil to lymphocyte ratio, and platelets to lymphocyte ratio in patients with ovarian cancer (P<0.05). The same results were also observed in advanced groups and early groups. While between optimal cytoreduction and suboptimal cytoreduction, there were significant differences in platelets, monocytes, neutrophil to lymphocyte ratio, and platelets to lymphocyte ratio (P<0.05). Conclusions The cytoreduction outcome and pathological staging of ovarian cancer are closely related to the preoperative blood cell count. Blood cell count is important for the identification of benign and malignant ovarian tumors, cytoreduction outcome and the prediction of pathological staging, and may be of significance to the monitoring and prognosis of the disease. Key words: Ovarian neoplasms/SU/PA/BL; Neoplasm staging; Blood cell count

ASSESSMENT OF THE RISK OF METASTASIS IN PATIENTS WITH ENDOMETRIAL CARCINOMA

Endometrial cancer can be detected early, and it is considered a disease with good prognosis. In some patients, it may have an aggressive course with an unfavorable outcome. The reason for lethal outcome may be the progression and metastasis of malignant disease as well as common comorbidities in this group of patients. The aim of the study was to define the risk factors for metastasis in patients with endometrial carcinoma. The study is a retrospective one. It included 200 patients with endometrial carcinoma. Several parameters were recorded: patient's age, histological type of the tumor, grade of disease, stage of disease at the time of the initiation of treatment, applied therapy and the emergence of local recurrence and distant metastases. Standard statistical procedures were used: Student's t-test, analysis of variance, univariate and multivariate Cox regression analysis. Quantitative statistical analysis was carried out on the computer. Estimation was performed using SPSS software version 10.0 and StatCalc program of EPI-INFO software package version 6. The appearance of metastatic disease in 200 patients with endometrial cancer was monitored. Metastatic disease was registered in 76 patients (38.2%). The percentage of patients with metastases is proportional to the stage of the disease and is 74.1% for stage I, 60% for stage II, and 25.8% for stage III. All patients with stage IV had metastatic disease at the time of the diagnosis. Patients with metastases have significantly higher risk of lethal outcome. Risk factors for metastatic disease are: older age, higher stage of disease, suboptimal cytoreduction, deep myometrial invasion, use of adjuvant chemotherapy.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma

ObjectiveMost molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. MethodsSubjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. ResultsPNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). ConclusionsOne-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

Patterns and Prognostic Importance of Hepatic Involvement in Patients with Serous Ovarian Cancer: A Single-Institution Experience with 244 Patients

Purpose To evaluate the frequency, patterns, and prognostic importance of metastatic hepatic involvement in serous ovarian cancer. Materials and Methods This institutional review board-approved retrospective study, with waived informed consent, included 244 patients with pathologically proven serous ovarian cancer (mean age ± standard deviation, 59 years ± 10.7; range 19-93 years). Electronic medical records and all available imaging studies over a median follow-up of 44 months (interquartile range [IQR], 27-70) were reviewed to identify the frequency of liver parenchymal invasion (LPI) from perihepatic peritoneal metastasis and hematogenous liver metastases. The associations and prognostic importance of LPI and hematogenous metastases were studied by using univariate and multivariate Cox proportional analysis. Results Eighty-four of 244 patients (34%) developed perihepatic metastases, of whom 55 (23%) developed LPI after median of 43 months (IQR, 25-63). Hematogenous hepatic metastases developed in 38 of 244 patients (16%) after median of 42 months (IQR, 26-64). At multivariate analysis, age (P = .008; hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 1.009, 1.07) and suboptimal cytoreduction (P = .03; HR, 2.13; 95% CI: 1.12, 4.07) were associated with LPI. Increasing age (P = .01; HR, 1.04; 95% CI: 1.008, 1.08), high-grade tumor (P = .01; HR, 6.75; 95% CI: 1.44, 120.5), and advanced stage (P = .03; HR, 3.16; 95% CI: 1.94, 4.56) were associated with hematogenous metastases. Overall survival with and without LPI was similar (median, 80 months; IQR, 50-not reached vs 123 months; IQR, 49-279; P = .6). Hematogenous metastases were associated with significantly shorter survival at univariate (median 63 months, IQR 43-139 vs 145 months, IQR 50-not reached; P = .006) and multivariate analyses (P = .03; HR, 1.88; 95% CI: 1.14, 3.28). Conclusion Differentiating hematogenous metastases and LPI is important for radiologists; hematogenous metastases are associated with shorter survival, while LPI does not adversely affect survival and prognostically behaves like peritoneal disease. © RSNA, 2016.

Tertiary Cytoreduction for Recurrent Epithelial Ovarian Cancer: a Multicenter Study in Turkey.

The purpose of this study was to determine the benefit of tertiary cytoreductive surgery (TC) for secondary recurrent epithelial ovarian cancer (EOC), focusing on whether optimal cytoreduction has an impact on disease-free survival, and whether certain patient characteristics could identify ideal candidates for TC. Retrospective analysis of secondary recurrent EOC patients undergoing TC at three Turkish tertiary institutions from May 1997 to July 2014 was performed. All patients had previously received primary cytoreduction followed by intravenous platinum-based chemotherapy and secondary cytoreduction for first recurrence. Clinical and pathological data were obtained from the patients' medical records. Survival analysis was caried out using the Kaplan Meier method. Actuarial curves were compared by the two tailed Logrank test with a statistical significance level of 0.05. Median age of the patients was 49.6 years (range, 30-67) and thirty-eight (72%) had stage III-IV disease at initial diagnosis. Twenty six (49%) had optimal and 27 (51%) suboptimal cytoreduction during tertiary debulking surgery . Optimal initial cytoreduction, time to first recurrence, optimal secondary cytoreduction, time interval between secondary cytoreduction and secondary recurrence, size of recurrence, disease status at last follow-up were found to be significant risk factors to predict optimal TC. Optimal cytoreduction in initial and tertiary surgery and serum CA-125 level prior to TC were independent prognostic factors on univariate analysis. Our results and a literature review clearly showed that maximal surgical effort should be made in TC, since patients undergoing optimal TC have a better survival. Thus, patients with secondary recurrent EOC in whom optimal cytoreduction can be achieved should be actively selected.