Surgical Efforts Might Mitigate Difference in Response to Neoadjuvant Chemotherapy in Stage IIIC–IV Unresectable Ovarian Cancer: A Case-Control Multi-institutional Study

2018 ◽  
Vol 28 (9) ◽  
pp. 1706-1713 ◽  
Author(s):  
Francesco Raspagliesi ◽  
Giorgio Bogani ◽  
Laura Matteucci ◽  
Jvan Casarin ◽  
Ilaria Sabatucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Pathological Examination ◽  
Survival Outcomes ◽  
Response To Chemotherapy ◽  
Propensity Matching ◽  
Disease Free ◽  
Response To Neoadjuvant Chemotherapy

ObjectiveThe aim of the study was to evaluate outcomes of patients with unresectable advanced ovarian cancer experiencing complete response (CR) to neoadjuvant chemotherapy.MethodsData of consecutive patients undergoing neoadjuvant chemotherapy plus interval debulking surgery (IDS) were retrospectively reviewed in 4 Italian centers. Using a propensity-matching algorithm, we compared data of patients achieving CR with neoadjuvant chemotherapy (no macroscopic either microscopic residual disease (RD) at the time of IDS) with patients achieving partial response (PR). This latter group was stratified by the presence of RD (RD = 0 vs RD > 0).ResultsOverall, 193 had IDS after neoadjuvant chemotherapy: 25 (13%), 81 (41.9%), and 74 (38.3%) patients had CR, PR with RD of 0, and PR with RD of more than 0, respectively. In addition, 13 (6.7%) patients had no macroscopic disease detected at DS but just microscopic disease at pathological examination. For the study purpose, 25 patients achieving CR were matched (1:2) with 50 patients having PR and RD of 0 and 50 patients having PR and RD of more than 0. As the result of propensity matching, baseline characteristics were similar between groups. Comparing survival outcomes of patients having CR and PR with RD of 0, we observed that type of response to chemotherapy did not influence disease-free (hazard ratio = 1.53 [95% confidence interval = 0.88–2.66], P = 0.127) and overall (hazard ratio = 1.74 [95% confidence interval = 0.76–4.01], P = 0.189) survivals. Patients achieving CR experienced significantly better disease-free survival (P = 0.004) and a trend toward better overall survival (P = 0.06) than patients achieving PR with RD of more than 0 at IDS.ConclusionsComplete cytoreduction might mitigate the difference in response to neoadjuvant chemotherapy. The presence of RD at IDS is associated with worse survival outcomes.

scholarly journals AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas

2020 ◽  
Vol 9 (12) ◽  
pp. 4105
Author(s):  
Marko Hojnik ◽  
Nataša Kenda Šuster ◽  
Špela Smrkolj ◽  
Snježana Frković Grazio ◽  
Ivan Verdenik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Confidence Interval ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Developed Countries ◽  
Hazard Ratio ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Disease Free

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

scholarly journals Dynamic analysis of serum Ca-125 levels during neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer: a retrospective study

2020 ◽  
Vol 10 (1) ◽  
pp. 88
Author(s):  
Adarsh Dharmarajan ◽  
A. Remya ◽  
Aswathi Krishnan
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Ca 125 ◽  
Free Survival ◽  
Proportional Hazards Regression ◽  
Response To Chemotherapy ◽  
Neo Adjuvant Chemotherapy ◽  
Disease Free

Background: Assessment of CA-125 kinetics was commonly used as a tool for tumor response to chemotherapy in ovarian cancer patients. The study aimed to determine any logarithmic/linear relationship between pre-chemotherapy and pre-operative CA-125 levels in ovarian cancer.Methods: Total 52 patients who underwent neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery were included. CA-125 levels before starting chemotherapy, during chemotherapy and the preoperative value, with the date of measurement recorded. Cox’s proportional hazards regression was used to evaluate univariate and independent multivariable association with the effect of clinical, pathological and CA-125 kinetic parameters on outcome endpoints.  Results: The study couldn’t establish any relationship in logarithmic fall of CA-125 values among ovarian cancers as a result of neo-adjuvant chemotherapy. The disease-free survival among the patients was 12.2 months.Conclusions: There is an inverse relationship between serum CA-125 levels and survival in ovarian cancer. NACT resulted in adequate fall of CA-125 levels in most of the patients, but the rate of fall was not predictive of prognosis.

p53 Alterations Predict Tumor Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Series

2000 ◽  
Vol 18 (7) ◽  
pp. 1465-1473 ◽  
Author(s):  
Arnauld Cabelguenne ◽  
Hélène Blons ◽  
Isabelle de Waziers ◽  
Françoise Carnot ◽  
Anne-Marie Houllier ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
P53 Gene ◽  
P53 Mutations ◽  
P53 Antibodies ◽  
Response To Chemotherapy ◽  
P53 Status ◽  
Response To Neoadjuvant Chemotherapy

PURPOSE: The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance. PATIENTS AND METHODS: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy. RESULTS: Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P < .001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P < .04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P = .003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy. CONCLUSION: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.

scholarly journals SCD5 Expression Correlates with Prognosis and Response to Neoadjuvant Chemotherapy in Breast Cancer

2020 ◽  
Author(s):  
Weipeng Zhao ◽  
Linlin Sun ◽  
Xichuan Li ◽  
Jun Wang ◽  
Ye Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Response ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Tumor Biomarker ◽  
Expression Signature ◽  
Response To Chemotherapy ◽  
Response To Neoadjuvant Chemotherapy

Abstract Neoadjuvant chemotherapy (NACT) represents a standard option for breast cancer. Unfortunately, about 55% to 80% of breast cancer patients do not have a favorable response to chemotherapy. Highly specific tumor biomarker that can predict the pathological response to neoadjuvant chemotherapy is lacking. Stearoyl-CoA desaturase 5 (SCD5) is an integral membrane protein of the endoplasmic reticulum that participates in lipid metabolism. However, the role of SCD5 in breast cancer remains unclear. Our study aims to understand its expression signature, prognosis value and correlation with pathological response to NACT in breast cancer using public databases. Analysis of samples from public databases showed that SCD5 expression was down-regulated across human cancers and associated with more aggressive breast cancer phenotypes. Survival analysis revealed that SCD5 expression was related to prognosis in breast cancer, especially triple-negative breast cancer (TNBC). Integrated analysis of multiple public datasets indicated that SCD5 expression signature was associated with response to NACT, particularly in TNBC. Based on functional enrichment analysis, SCD5 was implicated in pathways involved in metabolism and cell cycle. SCD5-related biological functions included negative regulation of cell cycle, cell division and DNA repair. Moreover, a significantly negative correlation between SCD5 expression and several cell cycle regulators was noted. Taken together, SCD5 was involved in the development and progression of breast cancer and might be a predictive biomarker for response to NACT. These results provided information for us to better understand SCD5 from the perspective of bioinformatics and highlighted the clinical importance of SCD5 in breast cancer, especially TNBC.

Does endometriosis have an effect on the survival of women with synchronous endometrial and ovarian cancer?

2019 ◽  
Vol 11 (4) ◽  
pp. 185-193
Author(s):  
Engin Celik ◽  
Hale Goksever Celik ◽  
Hamdullah Sozen ◽  
Semen Onder ◽  
Merve Baktiroglu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Detrimental Effect ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Pathological Characteristics

Purpose: Synchronous endometrial and ovarian cancer is defined as the concurrent presence of ovarian cancer with endometrial cancer. We aimed to evaluate whether there is an effect of endometriosis on progression-free survival and overall survival of women with synchronous endometrial and ovarian cancer. We also compared these findings with the patients having endometrial-only tumors and ovarian-only tumors. Methods: The patients who underwent surgery for endometrioid or clear-cell endometrial-only tumors and/or ovarian-only tumors and synchronous endometrial and ovarian cancer between 2005 and 2016 were included in this cohort study. The effect of the presence of endometriosis on progression-free survival and overall survival in these women who met the criteria was determined using statistical methods. Women were also compared regarding their demographic, clinical, and pathological characteristics. Results: A total of 176 patients were included in this study. All histology types of tumors located in endometrium or ovary were endometrioid or clear-cell cancer. Endometriosis was present in 62 patients (35.2%), whereas adenomyosis was present in 44 patients (25%). Endometriosis was diagnosed more frequently in women with ovarian-only tumors and synchronous endometrial and ovarian cancer than those with endometrial-only tumors (59.2% vs 5.7%, p < 0.001 and 45.7% vs 5.7%, p < 0.001, respectively). The patients with endometriosis showed no significantly longer progression-free survival and overall survival (hazard ratio = 1.70; 95% confidence interval = 0.48–6.03; p = 0.408 and hazard ratio = 1.67; 95% confidence interval = 0.30–9.44; p = 0.562, respectively). The presence of endometriosis was a stronger predictor for progression-free survival and overall survival comparing with the presence of adenomyosis. Conclusion: The women with synchronous endometrial and ovarian cancer should be informed that endometriosis has no detrimental effect on progression-free survival and overall survival.

The N-Terminally Truncated p53 Isoform Δ40p53 Influences Prognosis in Mucinous Ovarian Cancer

2012 ◽  
Vol 22 (3) ◽  
pp. 372-379 ◽  
Author(s):  
Gerda Hofstetter ◽  
Astrid Berger ◽  
Regina Berger ◽  
Arijana Zorić ◽  
Elena I. Braicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Hazard Ratio ◽  
Histological Subtypes ◽  
Mutational Status

ObjectiveThe tumor suppressor p53 generates the N-terminally truncated isoforms Δ40p53 and Δ133p53 that possess the ability to modulate p53 function in vitro. The aim of the present study was to evaluate the clinical relevance of p53 isoforms in the main histological subtypes of ovarian cancer.MethodsΔ40p53, Δ133p53, and full-length p53 (FLp53) expression was determined in 45 mucinous, 30 endometrioid, and 91 serous ovarian cancer specimens as well as 42 normal ovarian tissues using reverse transcriptase–quantitative polymerase chain reaction. In a subgroup of mucinous ovarian cancer cases, Δ40p53 expression was examined using Western blot analysis. A functional yeast-based assay and subsequent sequencing were performed to analyze the p53 mutational status.ResultsIn endometrioid cancer specimens, Δ133p53 expression was significantly lower than in mucinous and serous cases (P = 0.016) or in normal tissues (P = 0.004). Mucinous cancer samples showed elevated Δ40p53 expression as compared with normal ovarian tissues (P = 0.003). In addition, high Δ40p53 expression constituted an independent prognostic marker for recurrence-free but not for overall survival in patients with mucinous ovarian cancer (hazard ratio, 0.267; 95% confidence interval, 0.094–0.756 [P = 0.013]; hazard ratio, 0.453, 95% confidence interval, 0.193–1.064 [P = 0.069]). Western blot analysis confirmed the presence of p53β and Δ40p53α in a subset of patients with mucinous ovarian cancer. Expression of p53 isoforms was not associated with p53 mutational status or clinicopathologic parameters.ConclusionsWe show that expression of p53 isoforms differs in histological subtypes, thus supporting the hypothesis that histological subtypes represent distinct disease entities. In addition, we provide first evidence for a favorable role of Δ40p53 in patients with mucinous ovarian cancer.

Is there a CA-125 level that predicts negative second look surgery (SLS) in patients with advanced epithelail ovarian cancer (EOC)?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15042-15042
Author(s):  
S. Sharma ◽  
P. Singhal ◽  
K. Odunsi ◽  
S. Lele
Keyword(s):  
Ovarian Cancer ◽  
Disease Free Survival ◽  
Disease Status ◽  
Primary Treatment ◽  
Ca 125 ◽  
Primary Therapy ◽  
Second Look ◽  
Kaplan Meier ◽  
Response To Chemotherapy ◽  
Disease Free

15042 Background: The value of second look surgery (SLS) in advanced epithelial ovarian cancer (EOC) has been has been questioned because performing this procedure has not been associated with a clear survival advantage.However, SLS continues to be the most accurate means of documenting the response to chemotherapy, and therfore still used in investigational protocols. The primary purpose of this study was to assess the levels of CA 125 after treatment, that could predict absence of disease at SLS. Methods: Between 1998 and 2003, 98 stage III EOC patients who underwent optimal cytoreductive surgery, completed 6 cycles of platinum/paclitaxel chemotherapy, and were NED (no evidence of disease: normal CA 125, normal physical and radiological examination) were included in this study. SLS was performed at 6–8 weeks from completion of primary therapy. Patients with disease present at SLS were considered to have persistent disease and received second line chemotherapy. Patient demographics, surgical and chemotherapy treatments, and CA 125 levels prior to start and at completion of primary treatment were collected retrospectively. Survival was estimated by the Kaplan-Meier method. Results: Forty seven out of 98 (48%) of optimally debulked patients who were NED at completion of primary therapy underwent SLS. Twenty-five out of 47 patients (53%) had evidence of disease at SLS and 22 out of 47 patients (47%) were NED at SLS. The median disease free survival was 42 months (95% CI 16, 81) in patients with negative SLS compared with 17 months (95% CI 9, 45) in patients who did not undergo SLS (p = 0.03). Estimated 5-year survival in patients with negative SLS was 90% compared to 50% in patients who did not undergo SLS (p = 0.05). CA 125 levels of ≤ 10 after completion of primary therapy was predictive of negative SLS (p < 0.05). Conclusions: SLS evaluation of disease status appears to be a more accurate than standard clinical evaluation in patients who are NED at completion of their primary therapy. Negative SLS also appears to be a predictor of improved disease free and overall survival. Furthermore, CA 125 ≤ 10 is predictive of negative SLS in patients who are NED after completion of primary therapy. No significant financial relationships to disclose.

Effect of therapeutic GAS6/AXL inhibition of tumor and stromal cells on DNA damage and response to chemotherapy in ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14676-e14676 ◽  
Author(s):  
Mary M Mullen ◽  
Elena Lomonosova ◽  
Hollie M Noia ◽  
Lei Guo ◽  
Lindsay Midori Kuroki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Neoadjuvant Chemotherapy ◽  
Cell Viability ◽  
Mouse Models ◽  
Stromal Cells ◽  
Predictive Biomarker ◽  
Response To Chemotherapy

e14676 Background: Ovarian cancer is the leading cause of death due to gynecologic malignancy. Biomarkers to predict chemoresponse and novel therapies to target these proteins would be practice changing. We aim to establish serum and tissue GAS6 as a predictive biomarker of chemoresponse and to determine if AXL inhibition through sequestration of its ligand, GAS6, with AVB-S6-500 (AVB) can improve chemoresponse. Methods: AVB was supplied by Aravive Biologics. High grade serous ovarian cancer (HGSOC) tumor samples were obtained pre- and post-neoadjuvant chemotherapy. AXL and GAS6 expression were evaluated by immunohistochemistry and serum concentration. In vitro viability and clonogenic assays were performed on chemoresistant tumor (OVCAR8, OVCAR5, COV62, and POV71-hTERT) and stromal cells (CAF86) treated with chemotherapy +/- AVB. Mouse models (OVCAR8, PDX, OVCAR5) were used to determine if the combination of chemotherapy + AVB reduced tumor burden. Immunofluorescent assays targeting ɣH2AX were used to evaluate DNA damage. Results: Patients with high pretreatment tumor GAS6 expression ( > 85%, n = 7) or serum GAS6 concentrations ( > 25ng/mL, n = 13) were more likely to be resistant to neoadjuvant chemotherapy than those with low tumor GAS6 expression ( < 45%, n = 4) (P = 0.010) or low serum GAS6 concentrations ( < 15ng/mL, n = 5) (P = 0.002). Carboplatin plus AVB (2µM, 5µM) and paclitaxel plus AVB (1µM) resulted in decreased cell viability and clonogenic growth compared to chemotherapy alone (p < 0.05) in all tumor and stromal cell lines. Synergism was seen between carboplatin+AVB and paclitaxel+AVB with a weighted combination index < 1. In vivo tumor mouse models treated with chemotherapy+AVB had significantly smaller subcutaneous and intraperitoneal (IP) tumors than those treated with chemotherapy alone (3.1mg vs 64mg, P = 0.003 OVCAR8; 62mg vs 157mg, P = 0.0108 PDX subcutaneous model; 0.05mg vs 0.3669mg, P < 0.001 OVCAR5 IP model). Increased DNA damage was noted in tumor and stromal cells treated with carboplatin+AVB compared to carboplatin alone (OVCAR8, COV362, CAF86 P < 0.001). Conclusions: High GAS6 is associated with lack of neoadjuvant chemoresponse in HGSOC patients. The combination of chemotherapy with AVB decreases tumor cell viability, tumor growth, and an increase in DNA damage response.

Sign in / Sign up

Export Citation Format

Share Document