CA125 kinetic parameters predict optimal cytoreduction in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS). METHODS: The present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS. RESULTS: One hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97-0.99], p=0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56-7.10] (p=0.0008). CONCLUSION: Our data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS.

Value of Diaphragmatic Surgery During Interval Debulking Surgery.

BACKGROUND/AIM: The aim of this study was to assess the value of diaphragmatic surgery to achieve optimal debulking in patients with advanced ovarian cancer treated by neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: This is a retrospective review of the medical records of 182 patients. Diaphragmatic surgery was performed during interval debulking surgery (IDS) in 74 patients between January 2002 and December 2014. The patients were divided in 2 groups: with or without histological residual diaphragmatic disease. The time-course of serum CA125 levels, cytoreductive outcome, overall survival (OS) and relapse-free survival (RFS) were analyzed. Patients without diaphragmatic peritonectomy (DP) during IDS were included in the survival analysis. RESULTS: One hundred thirty-two (72.5%) patients had FIGO stage III disease and 43 (23.6%) patients had stage IV disease. Histological examination of DP was positive in 45 patients and negative in 29 patients. CA125 normalization after the 3rd cycle of NAC was significantly associated with negative DP. OS tended to be higher in the DP-negative group (37.8 months vs 19 months, p=0.1). Median OS was 40.7 months in the case of IDS without DP and 22 months in the case of IDS with DP (p=0.048). CONCLUSION: Evaluation of residual diaphragmatic disease can be difficult after NAC. The CA125 tumor marker appears to be a useful tool to define the indications for DP. Diaphragmatic surgery after NAC may be of limited value.

Serum CA125 and HE4 levels as predictors for optimal interval surgery and platinum sensitivity after neoadjuvant platinum-based chemotherapy in patients with advanced epithelial ovarian cancer.

BACKGROUND: The aim of this study is to evaluate a new tumour marker, HE4, and to compare it with CA125 in predicting optimal cytoreduction and response to chemotherapy. Thirty patients with advanced epithelial ovarian cancer and multiple sera harvested during neoadjuvant chemotherapy (NAC) were included. RESULTS: Based on ROC curves analysis, CA125 ≤ 75 UI/ml and HE4 ≤ 252 pmol/L after the 3rd cycles of NAC, with a sensitivity of 93.7 % and a specificity of 92.3 % (PPV = 93.7 % and NPV = 92.3 %), offered the best combination for predicting optimal cytoreduction. In addition, the HE4 value of 115 pmol/L is the best cut-off level for identifying platinum-sensitive patients. CONCLUSIONS: The introduction of HE4 as a new tool for predicting platinum-sensitivity and interval optimal cytoreduction is promising.

Dynamic Analysis of CA125 Decline During Neoadjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer as a Predictor for Platinum Sensitivity.

AIM: Our objective was to evaluate the kinetic parameters of serum CA125 during neoadjuvant platinum-based chemotherapy (NAC), in patients with epithelial ovarian cancer, in order to identify a surrogate marker of sensitivity to platinum. MATERIALS AND METHODS: Patients diagnosed between 2002 and 2009, and treated with NAC and interval debulking surgery, were included in the study. RESULTS: One hundred and forty-two patients met the study inclusion criteria. Fifty-four patients (38%) were platinum-sensitive (PFI >12 months). A CA125 level after the 3rd NAC cycle <35 UI/ml was significantly associated with improved overall survival (OS) and relapse-free survival (RFS). In the multivariate model, patients with a CA125 level after the 3rd NAC cycle >35 UI/ml were 3.8-times more at risk for PFI <12 months (95% CI=1.7-8.5, p<0.001). CONCLUSION: A CA125 level after the 3rd NAC <35 UI/ml is an independent predictor for tumor platinum-sensitivity.

Impact of Neoadjuvant Chemotherapy on the Rate of Bowel Resection in Advanced Epithelial Ovarian Cancer.

AIM: To assess the decrease in the number of bowel resections (BR) necessary to achieve complete cytoreduction (CC-0) in advanced epithelial ovarian cancer (EOC) permitted by neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Patients were selected from a population of advanced EOC cases diagnosed between 2002 and 2009 at the Curie Institute: 97 patients with Federation International of Gynecology and Obstetrics IIIc and IV with unresectable disease treated with NAC followed by interval debulking surgery were included. We proceeded to a systematic blinded review of all the surgical reports pre-and post-NAC by two different surgeons to assess the surgical procedures required to obtain CC-0. RESULTS: Before NAC, at least 84 patients (87%) would have required BR to obtain a CC-0 resection. At interval debulking surgery, 47 (49%) still required a BR, which corresponds to a decrease of 38% (p<0.0001). The same decrease was observed for resection of small bowel, colon and rectosigmoid, as follows: 54 to 17 (77% to 24%, p<0.0001), 45 to 19 (56% to 24%, p<0.0001) and 72 to 25 (90% to 31%, p<0.0001), respectively. The median overall survival (OS) among CC-0 patients with and without BR was 57 months [95% confidence interval (CI)=25-90 months] and 50 months [95% CI=43-57 months], respectively (p=0.71). The OS among patients without complete resection was significantly worse, with a median of 21 months (95% CI=17-32 months, p<0.0001). CONCLUSION: NAC significantly reduces the need and rate of BR in advanced EOC, but also of small bowel, colon and rectosigmoid resection. There is no loss of OS, after BR especially if the debulking surgery is complete.