Suboptimal Cytoreductive Surgery Research Articles

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125

ObjectivesTo assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. MethodsThis retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. ResultsWe observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level– but not HE4 – during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 – but not CA-125 – before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27–5.79). ConclusionMonitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial

The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. Dutch Cancer Foundation (KWF Kankerbestrijding).

TO STUDY AND ASSESS THE VALIDITY OF THE RISK OF MALIGNANCY INDEX(RMI-4) IN DISCRIMINATING BETWEEN BENIGN AND MALIGNANT OVARIAN MASSES

Introduction:The most fatal of all gynecological cancers is ovarian cancer. Of all gynecological cancers, it has the greatest fatality-to-case ratio. It is the 4th most prevalent cancer among women. The lifetime risk of being diagnosed with ovarian carcinoma is 1% to 1.5 %, with a nearly 0.5% chance of dying from it. Suboptimal primary cytoreductive surgery has great prognostic significance. The reason was because of inappropriate preoperative evaluation, which decides the kind of surgery being performed and the surgeons expertise of the surgeon in performing staging laparotomy if indicated. Hence, a gynecologist must be able to differentiate benign from the malignant ovarian mass. Several studies have revealed that the diagnosis of ovarian mass by investigations like Ultrasonogram, Doppler, MRI, CT has been proved to be uncertain despite the need for expertise. The goal of this study was to assess the ability of the Risk of Malignancy Index Scoring System (RMI- 4) in differentiating benign from malignant ovarian masses and to compare the scoring patterns to histopathological findings. Objectives: To validate the efficiency of the Risk of Malignancy Index(RMI-4) in discriminating benign and malignant ovarian tumors.To correlate the calculated value of the Risk of Malignancy Index(RMI-4) to the histopathological report.To evaluate the performance of individual parameters and the Risk of Malignancy Index(RMI-4) in differentiating benign and malignant ovarian tumors. Materials and methods: A prospective observational study in one year from date of approval from institutional ethical committee i. e from 2019 to 2021on women attending Gynecology outpatient and inpatient department diagnosed with an ovarian mass at Government Maternity Hospital, Tirupati. Results : 50 women with ovarian mass were selected for the study. Patients with endometriosis, fibroid uterus, Pelvic inflammatory disease, menstruation, pregnancy, ectopic pregnancy, and other non-gynecological conditions like peritonitis, diverticulitis, inflammatory bowel disease, tuberculosis, liver disease, recent surgery, are excluded. General and gynecological examinations were done for all cases. Ultrasound pelvis was done for all the patients and the presence of bilateral ovarian mass, multiloculated tumor, presence of solid areas, ascites, and extra ovarian metastasis was noted. An ultrasound score (U) of 1 was given if none or one of the features are found, and a score of 4 was given if two or more of these features were noted. Size of the tumor measured. A score of 1 was given for a tumor less than 7 cm and a score of 2 for a tumor size more than or equal to 7 cm size. Postmenopausal status was defined as more than one year of amenorrhea or age older than 50 years for women who had undergone hysterectomy they were scored as M=4. All other patients who did not meet these criteria were defined in a premenopausal status which scored M=1. The Risk of Malignancy Index (RMI-4) was calculated by using the formula: RMI-4 = U x M x S x CA 125. Laparotomy was done for all cases and the specimen was sent for histopathological examination which is the gold standard.90% of the tumors were benign and 10% were malignant.Prediction of malignancy by CA 125, ultrasound, and RMI-4 was analyzed.The optimal cut-off value of RMI-4 was 450 with a sensitivity of 95.56%, specificity of 100%, PPV of 100%, and NPV of 71.43%.Though the Specificity and PPV of CA125 were high, Sensitivity was less (86.67%).This study showed that RMI-4 had better performance than CA 125, USG score, and menopausal score in predicting malignancy. Conclusion:RMI-4 is a multimodal approach that is simple and easily applicable in the preoperative evaluation of a patient with an ovarian mass.Risk of Malignancy Index -4 (RMI-4) is a reliable method in discriminating benign and malignant ovarian mass preoperatively.Risk of Malignancy Index -4 (RMI-4) is a better scoring index in differentiating benign and malignant ovarian mass when compared to individual tests of ultrasonogram or CA125 level.The optimal cut-off point of Risk of Malignancy Index -4 (RMI-4) at which benign and malignant tumors can be discriminated was 450 in the present study.RMI-4 is the most useful scoring system in the proper selection of patient.Since the specificity of Risk of Malignancy Index -4 (RMI-4) was high, there is a potential role for this index in the selection of cases for conservative management or minimally invasive surgery in case of benign ovarian masses.

Unresectable Ovarian Cancer Requires a Structured Plan of Action: A Prospective Cohort Study

Patients with unresectable disease during cytoreductive surgery (CRS) for advanced-stage ovarian cancer are underreported. Knowledge of treatment and survival after surgery is limited. The aim of this study is to address the knowledge gap about postoperative treatment and survival of patients whose surgery was abandoned due to unresectability after abdominal exploration. Women with FIGO stage IIIB-IV epithelial ovarian cancer whose disease was considered to be unresectable during surgery were included in this prospective study, a post hoc analysis of the PlaComOv study. The unresectable disease was defined as the inability to achieve at least suboptimal CRS without attempted CRS after careful inspection of the entire abdomen. Preoperative clinical data, perioperative findings, postoperative treatment and survival data were analyzed. From 2018 to 2020, 27 patients were included in this analysis. Treatment ranged from the cessation of treatment to one or several lines of chemotherapy with or without maintenance therapy. The median overall survival was 16 (IQR 5-21) months (95%CI 14-18). At 24 months of follow-up, four patients (15%) were alive. This study indicated a two-year survival of 15%. Optimal treatment strategies in terms of survival benefits are still ill-defined. Further study of this specific group of patients is warranted. We advocate an (inter)national registry of patients with unresectable cancer and comprehensive follow-up.

Minilaparotomy, Cyfra21-1, and Other Predicting Factors for Suboptimal Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer: A Pilot Study

Currently, there is no reliable method to predict the result of the primary cytoreduction to decide whether to go on primary cytoreductive surgery or receive neoadjuvant chemotherapy. This study aimed to identify candidate predicting factors from clinical data, serum biomarkers, CT/MRI imaging, and minilaparotomy for suboptimal cytoreduction in women with advanced epithelial ovarian cancer. Women who were clinically suspicious of advanced-stage epithelial ovarian, fallopian tube, and peritoneal cancer undergoing primary cytoreductive surgery were recruited. Clinical data, abdominopelvic CT/MRI, and serum biomarkers, including CA125, HE4, and Cyfra21-1, were collected preoperatively. At the start of the surgery, a minilaparotomy incision was made, the peritoneal cavity was assessed, and the operating surgeons gave the impression of whether the optimal cytoreductive surgery would be attainable. Subsequently, the incision was extended as necessary, and the standard cytoreductive surgery was attempted. After the procedure completion, the surgical outcome (optimal vs. suboptimal cytoreduction) and other operative outcomes were recorded. The association between the potential predicting factors and the surgical outcome was examined. Fourteen patients were included in this pilot study. Twelve patients were diagnosed with primary ovarian or fallopian tube cancer, while two had ovarian metastasis from colorectal cancer. The optimal cytoreduction was achieved in eight women. After minilaparotomy, the surgeons could predict suboptimal surgery correctly in five out of six cases (OR: 24.12, 95%CI: 2.34-Inf., p<0.01). Moreover, no patient with the finding of rectosigmoid invasion from CT had optimal surgery (OR: 12.96, 95%CI: 1.26-Inf., p=0.03). Lastly, increased serum cyfra21-1(>8 ng/mL) and HE4 (>83 pmol/L) were significantly associated with suboptimal cytoreduction, with OR: 35.00, 95%CI: 1.74-702.99, p=0.02 and OR: 15.00, 95%CI: 1.03-218.30, p=0.05, respectively. The finding of rectosigmoid invasion from abdominal CT, increased serum cyfra21-1 and HE4, and the initial minilaparotomy impression were potentially associated with suboptimal cytoreduction.

Oncological and reproductive outcomes in patients with advanced-stage ovarian immature teratoma: Experience from a tertiary center (140)

Objectives: To evaluate the oncological and reproductive outcomes in patients with advanced-stage ovarian immature teratoma (IMT). Methods: We retrospectively reviewed the medical records of patients with advanced-stage IMT who were treated with surgery between January 1985 and December 2020. Fertility-sparing surgery (FSS) was defined as the preservation of the uterus and at least one adnexa. Oncological outcomes were compared between patients who underwent FSS and radical surgery. Patients who underwent FSS were also contacted to gather information about their menstrual history and reproductive outcomes. Results: Forty-six patients fulfilled the inclusion criteria, of whom 38 underwent FSS and eight were treated with radical surgery. Fifteen patients suffered recurrence after a median follow-up time of 74.2 months (range: 4.1–434.1 months). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69.1% and 89.9%, respectively. Multivariate analysis identified suboptimal cytoreductive surgery as the only independent risk factor for recurrence. There was no significant difference in DFS or OS between patients with different surgical procedures. Ten of the 15 relapsed patients had optimal salvage surgery, and all remained alive with no evidence of disease. Among the 32 patients who underwent FSS, 29 resumed menstruations after surgery, and five of seven patients who designed pregnancy achieved a total of five successful pregnancies. Objectives: To evaluate the oncological and reproductive outcomes in patients with advanced-stage ovarian immature teratoma (IMT). Methods: We retrospectively reviewed the medical records of patients with advanced-stage IMT who were treated with surgery between January 1985 and December 2020. Fertility-sparing surgery (FSS) was defined as the preservation of the uterus and at least one adnexa. Oncological outcomes were compared between patients who underwent FSS and radical surgery. Patients who underwent FSS were also contacted to gather information about their menstrual history and reproductive outcomes. Results: Forty-six patients fulfilled the inclusion criteria, of whom 38 underwent FSS and eight were treated with radical surgery. Fifteen patients suffered recurrence after a median follow-up time of 74.2 months (range: 4.1–434.1 months). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69.1% and 89.9%, respectively. Multivariate analysis identified suboptimal cytoreductive surgery as the only independent risk factor for recurrence. There was no significant difference in DFS or OS between patients with different surgical procedures. Ten of the 15 relapsed patients had optimal salvage surgery, and all remained alive with no evidence of disease. Among the 32 patients who underwent FSS, 29 resumed menstruations after surgery, and five of seven patients who designed pregnancy achieved a total of five successful pregnancies.

Evaluation of the prognostic value of lymphadenectomy for low-grade serous ovarian cancer: A case-control multicenter retrospective study

BackgroundThe prognostic value of lymphadenectomy in low-grade serous ovarian cancer (LGSOC) remains uncertain. Materials and methodsA retrospective analysis of 155 patients with LGSOC who underwent surgery over a ten-year period (2011–2020) was performed. The propensity score matching (PSM) algorithm was performed between the lymphadenectomy and no lymphadenectomy groups, and Kaplan-Meier analyses were conducted to evaluate clinical prognosis. Finally, univariate and multivariate Cox proportional hazards regression analyses were performed to analyze high-risk factors associated with clinical prognosis. ResultsIn the pre-PSM cohort, 110 (71.0%) patients underwent lymphadenectomy. Of these, 54 (34.8%) experienced recurrence, and 27 (17.4%) died. There were statistical differences in disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016) in the post-PSM cohort. In the subgroup analysis, there were no statistically significant differences in DFS (P = 0.449) or OS (P = 0.167) in the FIGO I/II cohort. However, in the FIGO III/IV cohort, DFS (P = 0.011) and OS (P = 0.046) were statistically different between the two groups. Age > 50 years, FIGO stage III/IV, and suboptimal cytoreductive surgery were risk factors associated with prognosis. In the lymphadenectomy group, the histological status of pelvic lymph nodes had no significant effect on DFS (P = 0.205) or OS (P = 0.114). ConclusionLymphadenectomy was associated with DFS and OS, particularly in patients with advanced LGSOC patients. Age > 50 years, advanced FIGO stage III/IV, and suboptimal cytoreductive surgery were high-risk factors associated with clinical prognosis in patients with LGSOC.

Oncological and Reproductive Outcomes in Patients With Advanced-Stage Ovarian Immature Teratoma: Experience From a Tertiary Center.

ObjectiveTo evaluate the oncological and reproductive outcomes in patients with advanced-stage ovarian immature teratoma (IMT).MethodsWe retrospectively reviewed the medical records of patients with advanced-stage IMT who were treated with surgery between January 1985 and December 2020. Fertility-sparing surgery (FSS) was defined as preservation of the uterus and at least one adnexa. Oncological outcomes were compared between patients who underwent FSS and radical surgery. Patients who underwent FSS were also contacted to gather information about their menstrual history and reproductive outcomes.ResultsForty-six patients fulfilled the inclusion criteria, of whom 38 underwent FSS and eight were treated with radical surgery. Fifteen patients suffered recurrence after a median follow-up time of 74.2 months (range: 4.1–434.1 months). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69.1% and 89.9%, respectively. Multivariate analysis identified suboptimal cytoreductive surgery as the only independent risk factor for recurrence. There was no significant difference in DFS or OS between patients with different surgical procedures. Ten of the 15 relapsed patients had optimal salvage surgery and all remained alive with no evidence disease. Among the 32 patients who underwent FSS, 29 resumed menstruation after surgery, and five of seven patients who designed pregnancy achieved a total of five successful pregnancies.ConclusionsOvarian IMT has a favorable prognosis, even when diagnosed at an advanced stage. FSS is feasible in patients with advanced-stage IMT who wish to preserve their fertility. Patients may benefit from optimal cytoreductive surgery during initial and salvage surgery.

Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics.

ObjectiveEmerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.MethodsWe enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model.ResultsThe sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2% vs. 82.2%, P=0.044), and the detection rate of CTCs was higher than the positive rate of CA125 (74.5% vs. 58.2%, P=0.069) in early-stage patients (stage I and II). The detection rate of CTCs was significantly higher in patients with ascitic volume ≥500 mL, suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy (P<0.05). The detection rate of CTCEpCAM+ and CTCMUC1+ was significantly higher in chemo-resistant patients (26.3% vs. 11.9%; 26.4% vs. 13.4%, P<0.05). The median progression-free survival time for CTCMUC1+ patients trended to be longer than CTCMUC1− patients, and overall survival was shorter in CTCMUC1+ patients (P=0.043). ConclusionsOur study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTCEpCAM+ and CTCMUC1+ had predictive value for chemotherapy resistance, and the detection of CTCMUC1+ suggested poor prognosis.

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.

Disparities in ovarian cancer survival at the only NCI-designated cancer center in Kansas

BackgroundThis study examined the impact of geographic distance on survival outcomes for patients receiving treatment for ovarian cancer at the only NCI-designated cancer center (NCI-CC) in Kansas. MethodsWe identified ovarian cancer patients treated at the University of Kansas Cancer Center between 2010 and 2015. Demographic factors and clinical characteristics were abstracted. The main outcome measure was overall survival according to geographic distance from the institution. Kaplan Meier survival curves and Cox proportional hazard models were generated using SAS v9.4. Results220 patients were identified. Survival analysis based on distance from the institution demonstrated that patients who lived ≤10 miles from the institution had worse overall survival (p = 0.0207) and were more likely to have suboptimal cytoreductive surgery (p = 0.0276). Lower estimated median income was also associated with a 1.54 increased risk of death, 95% CI (1.031–2.292), p = 0.0347. ConclusionsWe determined that ovarian cancer survival disparities exist in our patient population. Lower rates of optimal cytoreductive surgery has been identified as a possible driver of poor prognosis for patients who lived in proximity to our institution.

Improved prognosis for recurrent epithelial ovarian cancer by early diagnosis and 125I seeds implantation during suboptimal secondary cytoreductive surgery: a case report and literature review

BackgroundEpithelial ovarian cancer (EOC) has the worst prognosis in all of gynecologic malignant tumors because of its high recurrence and eventually chemo-resistance. Early diagnosis of recurrence is crucial to avoid diffuse dissemination. Failure of traditional treatment in recurrent epithelial ovarian cancer remains a challenge for clinicians. On the other hand, 125I brachytherapy has been accepted as a useful and hopeful treatment for multiple advanced cancers in recent years. However, its success in advanced epithelial ovarian cancer is limited. Here we report a case of recurrent ovarian cancer who had been early diagnosis of isolated recurrence and successfully treated with 125I seeds implantation during suboptimal cytoreductive surgery.Case presentationA 59-year-old woman presented with recurrent epithelial ovarian cancer who have had a history of ovarian cancer stage IIIB and an R0 resection had been achieved nearly 2 years before presented in our hospital. She underwent suboptimal secondary cytoreductive surgery after four cycles of chemotherapy with little effectiveness and severe chemotherapy-related side effects. Approximately 70% of the cancer-bulk was resected during surgery. For residual lesion which fixed around the right ureter and right external iliac vessel, 125I seeds implantation was performed. Postoperatively, the patient was treated with two cycles of combination chemotherapy with paclitaxel and carboplatin. The patient was free of disease at 26 months’ follow-up period.ConclusionIn recurrent EOC patients with unresectable isolated lesion, salvage 125I seeds implantation are feasible and may contribute to survival.

Prognostic relevance of high pretreatment CA125 levels in primary serous ovarian cancer.

The objective of the present study was to analyze the prognostic relevance of pretreatment serum CA125 ≥500 U/ml and its role as a non-invasive factor for estimating optimal cytoreduction (≤1 cm) in primary serous ovarian cancer. Clinicopathological parameters and CA125 levels prior to primary cytoreductive surgery were retrospectively evaluated in all 261 consecutive patients with primary epithelial ovarian cancer from a single centre. Inclusion criteria were existing preoperative CA125 level, serous ovarian cancer and performed full primary treatment (surgery/platinum-based chemotherapy). A total of 136 patients met the criteria. Among them, 74 patients had CA125 ≥500 U/ml. The other 62 patients that met the aforementioned criteria and had CA125 <500 U/ml were defined as controls. The present study tested cut-off CA125 values to detect subgroups affecting prognosis. The goal was to evaluate patients with optimal cytoreduction (R≤1 cm). Univariate analyses were performed with PASW to identify clinicopathological parameters associated with the pretreatment CA125 level. For survival analyses, a cut-off-value of CA125 ≥500 U/ml was used to identify the association between preoperative CA125 levels, resection status and prognosis. To test significant differences between examined groups, Student's t-test and the Mann-Whitney test were used. P<0.05 was considered to indicate a statistically significant difference. Significantly worse prognosis in terms of overall survival (P=0.023) and progression-free survival (P=0.011) was detected in the CA125 ≥500 U/ml group of optimally cytoreduced patients compared with in the CA125 <500 U/ml group. The complete cytoreduction rate was higher in CA125 <500 U/ml (33.9%) vs. CA125 ≥500 U/ml (21.6%). A CA125 level >1,404 U/ml had a higher rate of suboptimal cytoreduction (32.4%) compared with lower CA125 levels. A pretreatment CA125 level ≥500 U/ml had significantly worse prognostic impact after optimal cytoreduction compared with CA125 <500 U/ml. The higher the CA125 level the higher the suboptimal cytoreduction rate. Patients with CA125 ≥500 U/ml may be candidates for an initial laparoscopic approach to specify resectability and to determine how to proceed. Overall, CA125 levels appear to be helpful in predicting suboptimal cytoreductive surgery for patients with primary ovarian cancer, but should be interpreted together with clinical and radiologic findings. This may improve defining the optimal treatment strategy in these patients.

Pre-operative evaluation of epithelial ovarian cancer patients: Role of whole body diffusion weighted imaging MR and CT scans in the selection of patients suitable for primary debulking surgery. A single-centre study

Purposeto evaluate the accuracy of Whole Body MRI including Diffusion-Weighted Imaging sequences (WB DWI MR) in the assessment of sites of disease in epithelial ovarian cancer (EOC), in comparison to CT; to evaluate whether a clinical-radiological score may predict suboptimal cytoreductive surgery. Methodspatients with suspected EOC who underwent pre-operative WB DWI MR were included; CT scans were recorded. Data recorded included: age, staging, dates of examinations and surgery; tumour markers; sites of disease at imaging scans and at surgery. For calculation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB DWI MR and CT, surgical evaluation represented the gold standard. The accuracy of WB DWI MR and CT was compared. The association between clinical and radiological criteria with sub-optimal cytoreduction was tested to identify a final model to predict sub-optimal cytoreduction. Results92 patients were included; 77/92 (83.7 %) were optimally cytoreduced. Sixty-six CT and 92 MR examinations were evaluated. WB DWI MR showed overall higher accuracy than CT in assessing all sites, but it performed significantly better than CT specifically for involvement of mesentery, lumbo-aortic lymph nodes, pelvis, large bowel, sigmoid-rectum. The predicting score for suboptimal cytoreduction included: mesenteric carcinomatosis; mesenteric retraction; large bowel carcinomatosis. ConclusionsIn pre-operative evaluation of EOC patients, WB DW MRI is accurate for assessment of multiple sites and it is significantly more accurate than CT for specific unresectable sites. In our series, significant sites of disease for suboptimal cytoreduction were mesenteric carcinomatosis, mesenteric retraction and large bowel carcinomatosis.

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.

The effectiveness of targeted therapy in the treatment of common forms of ovarian cancer

Purpose of the study. To evaluate the effectiveness of the targeted drug bevacizumab (Avegra®) in the complex treatment of patients with common forms of ovarian cancer after suboptimal cytoreductive surgical interventions. Materials and methods. For the period from January 2017 to November 2018. A clinical study included and treated 71 patients with a diagnosis of ovarian cancer, stage IIIC-IV disease. The prevalence of the tumor process was estimated according to the classification of FIGO and TNM (2009). Patients were randomized into two groups. The first group included 31 patients, the treatment was carried out according to the scheme: paclitaxel 175 mg/m2, carboplatin AUC 6, bevacizumab 15 mg/kg with an interval of 21 days. The second group (control group) included 40 patients who received standard drug therapy. Interval suboptimal cytoreductive surgery was performed in all patients - hysterectomy with appendages, epiploic resection, peritonectomy. Evaluation of the effectiveness of immediate and remote The results were carried out by the method of statistical processing using the program Statistic 6.0. Results. According to the criteria of RESIST 1.1 in the first group, a complete response was registered in 25.8%, a partial response in 51.6%, stabilization of the disease in 12.9%, progression of 9.6% of cases. In the second group, the complete response was in 20% of cases, a partial response was 45%, stabilization was 22.5%, progression was 12.5%. The median overall survival in the first group was 16.5 months аgainst 10.1 months in the second group.

Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian cancer based on preoperative and intraoperative determination of the peritoneal carcinomatosis index

BackgroundThe peritoneal carcinomatosis index (PCI) can be used to quantify the tumor burden in patients with advanced ovarian cancer. The aim of the present study was to establish a predictive model for suboptimal cytoreductive surgery (SCS) (residual tumor of > 1 cm) using preoperative and intraoperative determination of the PCI.MethodsIn total, 110 consecutive patients treated for advanced ovarian cancer during a 4-year period in our institution were assessed. Eighty of these patients were eligible for primary debulking surgery and thus included in the present study. All data were prospectively collected and retrospectively evaluated. We determined the PCI both preoperatively and intraoperatively and assessed postoperative complications.ResultsA PCI of > 20 was the best cut-off with which to predict a risk of SCS among all three diagnostic techniques assessed in this study (computed tomography, laparoscopy, and laparotomy). Intraoperative PCI determination was associated with the lowest risk of false negatives for SCS when detecting a PCI of < 20. The combination of preoperative computed tomography and laparoscopy, when both techniques predicted SCS, was associated with the lowest risk of false positives for SCS when detecting a PCI of > 20.ConclusionThe combination of computed tomography and laparoscopy to obtain the PCI can help to determine which patients with advanced ovarian cancer are suitable for primary debulking surgery and which should undergo neoadjuvant chemotherapy.

ПРОГНОЗУВАННЯ ЕФЕКТИВНОСТІ ЛІКУВАННЯ ХВОРИХ НА РАК ЯЄЧНИКІВ

Мета дослідження – вивчення медико-біологічних основ прогнозування ефективності платинової хіміотерапії та підвищення чутливості пухлини до хіміотерапії першої лінії.Матеріали та методи. З 2007 до 2011 року було обстежено 189 пацієнток з аденокарциномою яєчників III–IV стадії, яким після субоптимальної або неоптимальної циторедуктивної операції у післяопераційному періоді були проведені курси ад’ювантної хіміотерапії препаратами платини. Критерієм розподілу на групи була чутливість пухлини до препаратів платини. Результати дослідження та їх обговорення. Показано, що для пацієнток з РЯ є характерним напруження саногенетичних механізмів організму. Стан саногенезу в організмі пацієнток, хворих на рак яєчників, впливає на чутливість або рефрактерність пухлини до хіміотерапії препаратами платини. До маркерів прогнозу платинорезистентності відносяться генетична обтяженість (наявність мутантних алелів поліморфізмів BRCA1 5832insC та BRCA2 6174delAG у гетеро- та гомозиготному варіантах, мікросателітної нестабільності), висока активність циклінів D та E, підвищення рівнів катехоламінів, високий ступінь експресії оксиду азоту, ступінь гіперурикемії, активність експресії рецепторів до епідермального фактора росту та активність CAS 20q13. У жінок з наявністю вказаних факторів доцільно застосовувати медикаментозну корекцію дисрегуляційних порушень.Висновок. При ймовірній платинорезистентності доцільно на фоні стандартної терапії першої лінії застосовувати медикаментозну корекцію дисрегуляційних порушень (донатори оксиду азоту, детоксиканти, антиурикемічні засоби). При прогнозованій платиночутливості стандартна терапія першої лінії може бути доповнена засобами, які покращують переносимість терапії, але використання медикаментозної корекції дисрегуляційних порушень є недоцільним.

Персоніфіковане лікування хворих на рак яєчників

Актуальність проблеми. Сьогодні «золотим стандартом» лікування раку яєчників (РЯ) стадій IС-IIIC є оперативне втручання з наступним курсом післяопераційної хіміотерапії препаратами платини. До 40% хворих із РЯ є первинно резистентними або рефрактерними (тобто не чутливими) до платини. Прогнозування чутливості пухлини до препаратів платини та застосування патогенетично обґрунтованих методів підвищення чутливості пухлини до платини є актуальною проблемою онкогінекології. Метою роботи було покращення безпосередніх та відділених результатів лікування хворих на епітеліальний рак яєчників шляхом підвищення чутливості пухлини до хіміотерапії першої лінії.Матеріал та методи дослідження. Обстежено 350 пацієнток з РЯ III–IV стадії, яким були виконані оптимальні, субоптимальні або неоптимальні циторедуктивні операції. Всі жінки були розділені 2 групи: І група (група контролю) — хворі на рак яєчників (n = 50), які одержують стандартну ад’ювантну платинову хіміотерапію першої лінії без використання розробленої концепції; ІІ група — 300 хворих, яких, на підставі виявлених критеріїв чутливості раку яєчників до хіміотерапії препаратами платини, було розділено на 3 підгрупи в залежності від прогнозованого ефекту платини: 1 підгрупа (n=77) - хворі з передбачуваною платинорефрактерністю, яким лікування було розпочато з хіміотерапії другої лінії; 2 підгрупа (n=98) — хворі з передбачуваною платинорезистентністю, яким на фоні стандартної ад’ювантної хіміотерапії першої лінії препаратами платини була проведена корекція саногенетичних порушень і дизрегуляційної патології; 3 підгрупа (n=125) — пацієнтки з передбачуваною чутливістю до препаратів платини, яким було проведено лікування препаратами платини відповідно до стандартів.Результати дослідження. Порівняльний аналіз даних щодо досягнення об’єктивного ефекту, стабілізації та контролю захворювання показав, що на відміну від І групи, у всіх пацієнток ІІ групи вдалося досягти прийнятних клінічних результатів. Зокрема, загальна виживаність у 2-й підгрупі ІІ групи зросла до 33,1±1,4 місяців, а у 3-й підгрупі – до 36,8±1,9 місяців. Це відповідає діапазонам 5,0-71,1 місяців та 3,0-73,3 місяців відповідно.Висновки. Застосування патогенетично обгрунтованої терапії, що враховує фармакогенетичні особливості дозволяє суттєво покращити результати лікування (OS до 33,1±1,4 місяців у пацієнтів з ймовірною платинорезистентністю та до 36,8±1,9 місяців у платиночутливих випадках; EFS – до 16,8±0,9 місяців та 29,5±1,1 місяців відповідно).

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma

Objectives: High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor overall survival. However, the clinical features of long-term (LT; >10 years) survivors have not been well characterized. Methods: A multicenter research consortium was established among 5 participating academic centers in the United States. Patient selection criteria included a diagnosis of stage III/IV high-grade serous ovarian, fallopian tube, or primary peritoneal carcinoma with at least 10 years of follow-up from the date of initial diagnosis. Nonserous, borderline tumors and low-grade serous subtypes were excluded. Results: A total of 203 LT survivors with HGSC were identified. Median age at diagnosis was 57 years (range 37–84 years). Most patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction (residual disease of no more than 1 cm in maximal diameter) was achieved in 143 (85.6%) patients, and 46.6% of all patients had a complete gross resection. After a median follow-up of 144 months, 88 (46.8%) patients did not develop recurrent disease. Twenty-one patients (11.2%) had 1 recurrence during the follow-up interval, 19 patients (10.1%) had 2 recurrences, and 60 patients (31.9%) had more than 2 recurrences. Of the 79 patients tested for BRCA1 and BRCA2 germline mutations, 43 (54.4%) carried a deleterious mutation. Of note, 24 (14%) patients had suboptimal cytoreductive surgery, 16 (11%) had a platinum-free interval of less than 12 months, and 100 (53%) with recurrent disease were surviving 10 or more years after diagnosis. Conclusions: Long-term survivors of advanced HGSC generally have clinical features including optimal surgical cytoreduction and platinum-sensitive disease. The majority of these patients will develop recurrent disease with many being treated with multiple therapeutic regimens. Future work will compare the clinical features of this LT survivor cohort of “exceptional” responders with the characteristics of HGSC patients with less favorable outcomes.