Clinical Significance of Apoptosis-Related Factors p53, Mdm2, and Bcl-2 in Advanced Ovarian Cancer

1999 ◽  
Vol 17 (7) ◽  
pp. 2061-2061 ◽  
Author(s):  
M. Baekelandt ◽  
G. B. Kristensen ◽  
J. M. Nesland ◽  
C. G. Tropé ◽  
R. Holm
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analyses ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Stage Iii ◽  
Related Factors ◽  
Tumor Biopsy ◽  
P53 Expression ◽  
Response To Chemotherapy

PURPOSE: To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. RESULTS: Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. CONCLUSION: p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.

Expression of Apoptosis-Related Proteins Is an Independent Determinant of Patient Prognosis in Advanced Ovarian Cancer

2000 ◽  
Vol 18 (22) ◽  
pp. 3775-3781 ◽  
Author(s):  
M. Baekelandt ◽  
R. Holm ◽  
J.M. Nesland ◽  
C.G. Tropé ◽  
G.B. Kristensen
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Disease Status ◽  
Stage Iii ◽  
Expression Data ◽  
Response To Chemotherapy ◽  
Independent Prognostic Significance ◽  
Related Proteins

PURPOSE: The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-XL, and Mcl-1 in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-XL and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis. RESULTS: Sixty-six percent of cancer cases expressed Bax, 62% Bcl-XL, and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P = .016) and less residual disease after surgery (P < .0001). In univariate analysis, Bax expression was associated with improved (P = .0004) prognosis and Mcl-1 expression with poorer (P = .011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P = .0115), together with residual disease status (P = .0016), differentiation grade (P = .0014), and the presence of ascites (P = .0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients’ expression data for p53, Bax, and Bcl-2 with their residual disease status (P < .00001). None of the factors studied was able to predict response to chemotherapy. CONCLUSION: The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

2009 ◽  
Vol 101 (03) ◽  
pp. 541-546 ◽  
Author(s):  
Andreas Scorilas ◽  
Sonia Markakis ◽  
Diane Kowalski ◽  
Robert L. Camp ◽  
Eleftherios P. Diamandis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Minimal Macroscopic Residual Disease (0.1–1 cm). Is It Still a Surgical Goal in Advanced Ovarian Cancer?

2016 ◽  
Vol 26 (5) ◽  
pp. 906-911 ◽  
Author(s):  
Luis M. Chiva ◽  
Teresa Castellanos ◽  
Sonsoles Alonso ◽  
Antonio Gonzalez-Martin
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Pubmed Database

ObjectiveThe objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1–10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm.MethodsA retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: “ovarian cancer and cytoreduction” or “ovarian cancer and phase III trial”. We selected those articles that contain information on both percentage of MMRD (0.1–1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery.ResultsThirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1–1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months.ConclusionsPatients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1–0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.

Prognostic significance of p53 immunostaining in epithelial ovarian cancer.

1994 ◽  
Vol 12 (1) ◽  
pp. 64-69 ◽  
Author(s):  
L C Hartmann ◽  
K C Podratz ◽  
G L Keeney ◽  
N A Kamel ◽  
J H Edmonson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Epithelial Ovarian Cancer ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Stage I ◽  
Stage Iii ◽  
P53 Expression ◽  
Independent Prognostic Significance ◽  
Grade 3

PURPOSE To evaluate the prognostic significance of p53 expression in epithelial ovarian cancer, including a subset of stage I patients, and to look for correlations between p53 expression and other disease parameters, including stage, grade, age, histologic subtype, second-look results, ploidy, and percent S phase. PATIENTS AND METHODS We analyzed p53 expression in 284 patients with epithelial ovarian cancer using immunohistochemical techniques in paraffin-embedded specimens. There were 36 patients with stage I disease, 20 with stage II disease, 186 with stage III disease, and 42 with stage IV disease. RESULTS p53 immunoreactivity was present in 177 cases (62%). p53 expression was associated with grade 3 to 4 disease (P = .003). The following factors were associated with a decrease in overall survival in a univarate analysis: stage III or IV disease (P = .0001), grade 3 or 4 disease (P = .0001), age above the median (P = .0002), and p53 reactivity (P = .04). In a multivariate analysis, stage, grade, and age retained independent prognostic significance. In the subset of 36 stage I patients, p53 positively approached statistical significance (P = .10) as a negative prognostic factor in a univariate analysis. CONCLUSION Abnormalities of p53 expression occur commonly in epithelial ovarian cancer. Although associated with decreased survival in a univariate analysis, this biologic marker did not retain independent prognostic significance in a multivariate analysis. p53 expression should be studied in a larger cohort of early-stage patients, where accurate prognostic information is needed to direct therapy.

Surgically documented response to intraperitoneal cisplatin, cytarabine, and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma.

1988 ◽  
Vol 6 (11) ◽  
pp. 1679-1684 ◽  
Author(s):  
M S Piver ◽  
S B Lele ◽  
D L Marchetti ◽  
T R Baker ◽  
L J Emrich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Intraperitoneal Chemotherapy ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iii ◽  
Second Line ◽  
First Line ◽  
Ovarian Adenocarcinoma ◽  
Specific Subset

Thirty-one evaluable patients with stages III and IV invasive ovarian adenocarcinoma were treated on a phase II protocol of second-line intraperitoneal cisplatin, cytarabine, and bleomycin. All 31 patients received first-line intravenous (IV) cisplatin-based chemotherapy; the size of the residual cancer was documented surgically before intraperitoneal chemotherapy in all patients. Response to intraperitoneal chemotherapy was documented by a third-look laparotomy in all patients not evidencing progression of disease clinically. There were eight responses (26%): five surgical complete responses and three surgical partial responses. Responders were patients with stage III ovarian cancer, small residual disease of less than or equal to 1 cm (primarily less than or equal to 5 mm), and patients who previously had responded to cisplatin-based IV chemotherapy. Of the 15 patients with stage III ovarian cancer, residual disease less than or equal to 1 cm, and those who had responded to first-line IV cisplatin-based chemotherapy, 53% (eight) responded to second-line intraperitoneal chemotherapy. Intraperitoneal chemotherapy as used in this phase II protocol would appear to be an effective second-line treatment in advanced ovarian cancer in this specific subset of patients.

Residual tumor status in clinical trials of advanced ovarian cancer: A systematic review

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15024-15024
Author(s):  
M. Beltrán ◽  
X. Hernández ◽  
C. Abal ◽  
M. Velasco ◽  
J. Rubio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Disease Status ◽  
Stage I ◽  
Stage Iii ◽  
Over Time

15024 Background: To determine whether the proportion of optimal disease status after surgery has changed along a defined period (the platinum era) on the setting of randomized clinical trials (RCT) in advanced ovarian cancer ( AOC). Methods: All RCT of chemotherapy for AOC in the platinum era (accrual period from 1980 to 2002) were searched. Studies were identified in an intensive review in MEDLINE, EMBASE and Cochrane Database, plus bibliographic references in the articles. We included those studies reporting stage, residual disease status and accruing both optimal and suboptimal disease. Simple linear regression models (slrm) were generated to evaluate the proportion of optimal disease status and of FIGO stages over time. Results are reported as two-side p values and 95% confidence intervals. Results: Seventy-five randomized studies, including 20,981 patients, fulfilled the inclusion criteria. Forty-two % of cases had optimal disease after surgery. Stage distribution was as follows: stage I-II, 7.5%, stage III, 72%, stage IV, 20%. Optimal disease status after surgery increased steadily over time, with larger proportions in more recent studies (r=.55; p < .005). Although there was a significant increase in stage I-II cases (r=.41; p < .005), inclusion of patients with stage III and stage IV did not change over time. Conclusions: Reported randomized clinical trials of chemotherapy for advanced ovarian cancer from 1980 to 2002 show a significant trend towards better postsurgical status of residual disease, with a larger proportion of patients with optimal disease in the more recent trials. This is marginally influenced by FIGO stage and therefore, occurs more likely from more extensive surgical debulking procedures. These changes in surgical approach result in an improvement of outcome, that may be independent of the postsurgical treatment used. No significant financial relationships to disclose.

scholarly journals When Should Surgical Cytoreduction in Advanced Ovarian Cancer Take Place?

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Igor E. Martinek ◽  
Sean Kehoe
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Timing Of Surgery ◽  
Load Prediction ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Interval Surgery ◽  
Histological Confirmation

Initial surgical management is commonly accepted to date as paramount in the treatment of women presenting with epithelial ovarian cancer and permits the assessment of the disease (staging), the histological confirmation of disease type and grade, and the practice of maximal debulking preceding platinum-based chemotherapy. Many studies have shown that the volume of residual disease after initial surgical cytoreduction inversely correlates with survival. Thus, women with optimal debulking performed by a trained specialist have improved median survival. In this review, we will focus on the answers gleaned from clinical trials on primary and interval surgery, which prompts the question on the timing of surgery in respect to chemotherapy. Interval debulking surgery (IDS) is secondary cytoreduction following primary debulking and is carried out in between the courses of chemotherapy. The major clinical trials and the latest systematic reviews seem unable to give any definitive guidance or recommendation for clinical practice. The choice of aggressive primary cytoreduction or upfront chemotherapy followed by second line surgical cytoreduction seems among others to have to be individualized according to tumour load, prediction of its resectability, and response to chemotherapy. The role of tumour biology must also be kept in mind. Finally, concrete answers are awaited on the timing of surgery from the ongoing prospective randomized control trials (CHORUS and EORTC 55971) though preliminary data from the latter have already been presented at major meetings (IGCS 2008; SGO 2009) and ignited strong debate.

scholarly journals Incorporating robotic surgery into the management of ovarian cancer after neoadjuvant chemotherapy

2019 ◽  
Vol 29 (9) ◽  
pp. 1341-1347 ◽  
Author(s):  
Jeremie Abitbol ◽  
Walter Gotlieb ◽  
Ziggy Zeng ◽  
Agnihotram Ramanakumar ◽  
Roy Kessous ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Robotic Surgery ◽  
Neoadjuvant Chemotherapy ◽  
Minimally Invasive ◽  
Cytoreductive Surgery ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iii ◽  
Time Period ◽  
Interval Cytoreduction

IntroductionWith the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III–IV ovarian cancer.MethodsAll patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III–IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III–IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery.ResultsA total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24–88), 78% had stage III disease, and the median follow-up time was 37 months (5.6–91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10–1250 mL), and the median hospital stay was 1 day.ConclusionRobotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.

scholarly journals Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

2020 ◽  
Vol 38 (30) ◽  
pp. 3528-3537
Author(s):  
Paul DiSilvestro ◽  
Nicoletta Colombo ◽  
Giovanni Scambia ◽  
Byoung-Gie Kim ◽  
Ana Oaknin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Interval Surgery

PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status ( BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

Sign in / Sign up

Export Citation Format

Share Document