The impact of interval cytoreduction and age in advanced-stage ovarian cancer: A GOG ancillary study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Stuart M. Lichtman ◽  
James Java ◽  
John L. Lovecchio ◽  
Dennis Chi ◽  
William P. Tew ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Residual Disease ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ancillary Study ◽  
Primary Surgery ◽  
The Impact

5056 Background: To determine if an age group exists for which interval cytoreductive surgery (ICS) in patients with suboptimal residual disease at primary surgery influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer. Patients with both optimal and suboptimal residual disease were included, and those with suboptimal residual were considered for ICS, with intent registered and stratified prior to randomization. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of patients with suboptimal residual disease. Statistical significance was set at p<0.05. Results: Among the entire eligible study population, 28% (n=1,042) were registered with suboptimal residual disease (> 1 cm) and 109 of these patients elected to undergo ICS. Hazard ratios (HR) were determined for patients undergoing ICS with reference to patients with suboptimal disease not undergoing ICS. Based on the most current follow-up data, the HR for progression or death was not statistically different between the groups, but the HR of death alone was significant at 0.72 (95% CI: 0.57–0.92, p=0.008). There was no significant association of age with ICS in either the PFS or the OS model. Conclusions: In this trial, a patient’s age did not influence the effect of ICS on PFS or OS. There is no demonstrable benefit in PFS associated with ICS, but there was a statistically significant improvement in OS. To elucidate this finding, further study is warranted, likely in the form of a meta-analysis incorporating data from other prospective trials.

The impact of interval from surgery to chemotherapy and age in advanced-stage ovarian cancer: A GOG ancillary study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5057-5057
Author(s):  
Andrew Menzin ◽  
James Java ◽  
John L. Lovecchio ◽  
Dennis Chi ◽  
William P. Tew ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Residual Disease ◽  
Statistical Significance ◽  
Advanced Ovarian Cancer ◽  
Time Interval ◽  
Primary Analysis ◽  
Risk Of Death ◽  
Ancillary Study ◽  
The Impact

5057 Background: To determine if an age group exists for which the interval from surgery to the initiation of chemotherapy influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer, including those with optimal and suboptimal residual disease. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. Chemotherapy was to be initiated within 12 weeks of primary surgery. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of the study population. Statistical significance was set at p<0.05. Results: The primary analysis of GOG 182 showed no differences in PFS or OS for any of the experimental arms when compared to the control regimen, and it was felt that the data from all arms could be aggregated for this analysis. Data for all regimens was pooled, and the time interval from surgery to chemotherapy was examined as a prognostic factor of survival. The interval had no statistically significant association with PFS (p=0.105). In the OS model, though, the functional form of the log interval was both significantly linear and nonlinear (p<0.001). After being flat until about 20 days (21.2 days; 95% CI, 15.0–28.2 days), the plot of log interval against log hazard increases, suggesting a changepoint time after which the associated risk of death increases. Conclusions: In this study, time interval from surgery to chemotherapy had no impact on PFS, but there was evidence of a potential time-dependent relationship with OS, which might be elucidated with a meta-analysis incorporating data from other prospective trials. Our observations did not appear to be influenced by patient age. Overall, these findings can reassure patients who are recuperating from extensive cancer surgery.

Potential Role of Lymphadenectomy in Advanced Ovarian Cancer: A Combined Exploratory Analysis of Three Prospectively Randomized Phase III Multicenter Trials

2010 ◽  
Vol 28 (10) ◽  
pp. 1733-1739 ◽  
Author(s):  
Andreas du Bois ◽  
Alexander Reuss ◽  
Philipp Harter ◽  
Eric Pujade-Lauraine ◽  
Isabelle Ray-Coquard ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Rank Test ◽  
Primary Surgery ◽  
The Impact

Purpose Primary surgery followed by platinum/taxane-based chemotherapy is the standard therapy in advanced ovarian cancer. The prognostic role of complete debulking has been well described; however, the impact of systematic pelvic and para-aortic lymphadenectomy and its interaction with biologic factors are still not fully defined. Methods This was an exploratory analysis of three prospective randomized trials (Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom trials 3, 5, and 7) investigating platinum/taxane-based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002. Results One thousand nine hundred twenty-four patients were analyzed. Lymphadenectomy was associated with superior survival in patients without gross residual disease. In patients with and without lymphadenectomy, the median survival time was 103 and 84 months, respectively, and 5-year survival rates were 67.% and 59.2%, respectively (P = .0166); multivariate analysis confirmed a significant impact of lymphadenectomy on overall survival (OS; hazard ratio [HR] = 0.74; 95% CI, 0.59 to 0.94; P = .0123). In patients with small residual tumors up to 1 cm, the effect of lymphadenectomy on OS barely reached significance (HR = 0.85; 95% CI, 0.72 to 1.00; P = .0497). For patients with small residual tumors and clinically suspect nodes, lymphadenectomy resulted in a 16% gain in 5-year OS (log-rank test, P = .0038). Conclusion Lymphadenectomy in advanced ovarian cancer might offer benefit mainly to patients with complete intraperitoneal debulking. However, this hypothesis should be confirmed in the context of a prospectively randomized trial.

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy

2020 ◽  
Vol 31 (1) ◽  
pp. 110-113
Author(s):  
Jole Ventriglia ◽  
Immacolata Paciolla ◽  
Carmela Pisano ◽  
Rosa Tambaro ◽  
Sabrina Chiara Cecere ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Free Survival ◽  
Primary Surgery

BackgroundChemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described.ObjectiveTo examine the incidence, duration, and reversibility of arthralgia.Patients and methodsA retrospective analysis was performed to describe the occurrence and outcome of arthralgia in 114 patients with advanced ovarian cancer, given first-line treatment with a combination of carboplatin, paclitaxel, and bevacizumab. Statistical analysis was performed to investigate a possible prognostic role of arthralgia, with progression-free survival as endpoint.Results47 of 114 patients (41%) developed arthralgia during therapy. All patients had grade 1 or grade 2 arthralgia. Toxicity persisted after the end of bevacizumab in 17/47 patients (36%). Median progression-free survival for patients without arthralgia was 18 months (95% CI 14 to 24) compared with 29 months (95% CI 21 to not reached) for patients experiencing arthralgia (p=0.03). In order to avoid possible biases related to treatment duration, a multivariable Cox proportional hazards model including toxicity as a time dependent variable and age, stage, and residual disease after primary surgery was performed. In this model no variable showed a statistically significant association with progression-free survival.ConclusionA high incidence of arthralgia (41%) was found and although rogression-free survival was worse for those patients who developed arthralgia, this was not maintained on multivariate analysis. Guidelines for treatment of this adverse event are needed.

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Survival ◽  
Stable Disease ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Second Look

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity.

1990 ◽  
Vol 8 (4) ◽  
pp. 705-714 ◽  
Author(s):  
F Lévi ◽  
M Benavides ◽  
C Chevelle ◽  
F Le Saunier ◽  
F Bailleul ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Experimental Studies ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Survival Times ◽  
Gynecology And Obstetrics ◽  
Pathological Cr

The efficacy and toxicity of the new anthracycline, 4'-0-tetrahydropyranyl doxorubicin (THP) (50 mg/m2 intravenous [IV] bolus) in association with cisplatin (100 mg/m2 IV as a 4-hour infusion) was assessed in 31 patients with advanced ovarian carcinoma. Twenty-eight patients were assessable for toxicity among whom 25 were assessable for response (International Federation of Gynecology and Obstetrics [FIGO] stage IIIa, four patients; IIIb, 15 patients; IV, six patients). Nine patients had received prior treatment. Patients were randomized to receive schedule (sch) A (THP at 6 hours, then cisplatin from 16 to 20 hours) or sch B (THP at 18 hours, then cisplatin from 4 to 8 hours). Sch A was hypothesized as less toxic since THP was best tolerated in the late rest span and cisplatin near the middle of the activity span in experimental studies. The rate of clinical complete response (CR) was 52%, that of partial response (PR) was 12%, and the overall clinical response rate (CR plus PR) was 64% (sch A, 73%; sch B, 57%). Median progression-free survival and survival times were, respectively, 10 and 19 months. Of 12 patients in clinical CR evaluated at second-look laparotomy, four had a pathological CR (33%), and three had microscopic residual disease (MD). The overall rate of pathological CR was 16%. Sch A was associated with less neutropenia (P = .10), thrombocytopenia (P less than .01), anemia (P less than .01), and renal toxicity (P less than .05) than sch B. Of four patients withdrawn for toxicity, three were on sch B (one death). Mean dose intensities (DIs) of THP and cisplatin, respectively, decreased by 30% and 47% over the five initial courses. Such decrease was significantly more pronounced for sch B than for sch A in previously untreated patients (P from 2-way analysis of variance [ANOVA] less than .01). THP-cisplatin is active against advanced ovarian cancer, and its toxicities can be significantly decreased by dosing THP in the early morning and cisplatin in the late afternoon as compared with THP in the evening and cisplatin the next morning.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
Author(s):  
Ezzeldin M Ibrahim ◽  
Ahmed A Refae ◽  
Ali M Bayer ◽  
Emad R Sagr
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Polymerase Inhibitors

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

Meta Analysis of Grade 3 and/or 4 Toxicities in Low-Grade Non-Hodgkin Lymphoma (LG-NHL) Patients Receiving Maintenance Rituximab (MR) Therapy: Impact of Schedule on Toxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2704-2704
Author(s):  
Chadi Nabhan ◽  
Dana Villines ◽  
Tina V. Valdez ◽  
Michele Ghielmini ◽  
Shu-Fang Hsu Schmitz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Comparative Trial ◽  
Progression Free Survival ◽  
Low Grade ◽  
Front Line ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2704 Background: MR has improved the outcome and progression-free survival (PFS) in patients with follicular lymphoma (FL) in front-line and relapsed settings. However, maintenance schedules have been empirically designed based on either B-cell depletion kinetics or rituximab levels, with no consensus on the optimal regimen. Overall, toxicities have been predictable and tolerable but the impact of MR schedule on toxicities has not been previously reported and could influence selection of maintenance regimens. Methods: Using PubMed, prospective clinical trials employing MR were identified. Data presented in abstract form or at meetings were deemed incomplete and thus excluded. Data were analyzed from published manuscripts as percentages of subjects experiencing an adverse event (AE). Percentages were considered as the unit of analysis as this adjusted for the uneven sample sizes. Data were collected for overall Grade 3 and/or Grade 4 toxicity (AE reported at any phase of treatment) and was further categorized as AE occurring during initial treatment or during MR. Grade 1 and 2 toxicities were excluded from meta-analysis, given lack of consistent reporting. No grade 5 toxicities were reported. The incidence, severity, and type of toxicity was analyzed by type of induction (Rituximab (R) vs. R plus chemotherapy), histology (FL vs. FL plus other LG-NHL), setting (front-line vs. relapsed), and MR schedule (one dose every 2 months vs. one dose every 3 months vs. 4 doses every 6 months). Results: Nine clinical trials involving 1,928 patients were included in this Meta analysis (4 of which were randomized controlled in the MR phase). Of those, 1,004 patients received MR. The mean percentage of Grade 3/4 toxicities during any phase of treatment was 26% (95% CI = 0.12–51.88) but when restricted to the MR phase; it was 12.88% (95% CI = 6.50–19.26). Toxicities were numerically higher in patients receiving R induction plus chemotherapy versus R induction alone and in patients receiving MR for relapsed disease versus newly diagnosed patients, but did not reach statistical significance (P = 0.661 and 0.517, respectively). However, patients receiving MR every 2 months were significantly more likely to develop grade 3 and 4 toxicities compared to patients receiving MR every 6 months (P = 0.005). No statistical differences were demonstrated between the 2 vs. 3 months schedules or when comparing the 3 vs. 6 months schedules (P = 0.342 and 0.267, respectively) (Table 1). Statistically significant differences were also found in studies restricted to FL versus others allowing non-FL histologies (P = 0.025) with the FL patients experiencing more toxicity than others. The most frequently reported toxicities were neutropenia and infections. There were no treatment-related deaths in any of the arms. Conclusions: Approximately 13% of patients receiving MR experience grade 3 and/or 4 toxicities, mainly consisting of neutropenia and infections. MR given every 6 months appears to provide the least grade 3 and 4 toxicities. There is a suggestion of increased toxicity in FL histologies. It is important to note that this meta-analysis did not address efficacy and only a true comparative trial can definitively establish the relative risk/benefit ratios amongst MR schedules. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Smith:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Visceral adiposity as a predictor of survival in patients with epithelial ovarian cancer receiving platinum and taxane-based chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17031-e17031
Author(s):  
Stuart-Allison Moffat Staley ◽  
Katherine Tucker ◽  
Jorge Oldan ◽  
Dominic T. Moore ◽  
Meredith Newton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Visceral Fat ◽  
Cox Regression ◽  
Subcutaneous Fat ◽  
Progression Free Survival ◽  
Visceral Adiposity ◽  
Oncologic Outcomes ◽  
The Impact ◽  
Fat Volume

e17031 Background: Obesity has been linked to worse outcomes in epithelial ovarian cancer (EOC), due to underlying metabolic dysfunction. Visceral fat (i.e. central obesity) compared to subcutaneous fat is more metabolically active and has been linked to higher rates of obesity-related comorbidities such as hypertension and diabetes, but less is known of the impact of increased visceral adiposity on EOC outcomes. Thus, our goal was to evaluate if visceral adiposity, as determined by computed tomography (CT) morphometric measurements, was associated with worse outcomes in EOC patients undergoing platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 12/2004 and 5/2016 who received neoadjuvant or adjuvant treatment with platinum and taxane-based chemotherapy were included. Data on age, stage, grade, histology, BMI, comorbidities, treatment approaches and outcomes were collected. CT images closest to the time of diagnosis were retrospectively evaluated for mid-waist visceral fat volume (VFV), mid-waist subcutaneous fat volume (SFV) and the ratio of mid-waist VFV/SFV. Visceral adiposity is commonly defined as a VFV/SFV ≥ 0.4. Cox regression models were used to analyze time-to-event outcomes. Results: Two hundred fifty-eight EOC patients were evaluated. Seventy-five percent of patients were diagnosed with Stage III or IV disease, with high grade serous as the most common histology (72%). Median age at diagnosis was 62.4 years. Approximately 65% were obese; the median BMI was 26.8 (IQR 23.1 – 32.6). The median VFV/SFV ratio was 0.46 (IQR 0.32 – 0.70). Patients were categorized into those with a VFV/SFV ratio greater than 0.4 or a ratio less than 0.4. When comparing these two groups, there was no difference in progression free survival (PFS) for women with a VFV/SFV ratio greater or less than 0.4 (p = 0.22). However, a VFV/SFV ratio of greater than 0.4 was associated with worse overall survival (OS) (p = 0.01). Conclusions: We found that visceral adiposity, defined as a VFV/SFV ratio greater than 0.4, appeared to be associated with decreased OS, but not PFS. These findings suggest that body fat distribution may be an important prognostic factor for EOC and should be further explored as we expect the obesity epidemic to continue and influence EOC oncologic outcomes.

scholarly journals The Role of Ultra-Radical Surgery in the Management of Advanced Ovarian Cancer: State or Art

2021 ◽  
Author(s):  
Felicia Elena Buruiana ◽  
Lamiese Ismail ◽  
Federico Ferrari ◽  
Hooman Soleymani Majd
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Radical Surgery ◽  
Advanced Ovarian Cancer ◽  
Holistic Approach ◽  
Gynaecological Malignancy ◽  
Optimal Debulking ◽  
Upper Abdomen ◽  
The Impact

The ovarian cancer, also known as “silent killer”, has remained the most lethal gynaecological malignancy. The single independent risk factor linked with improved survival is maximum cytoreductive effort resulting in no macroscopic residual disease. This could be gained through ultra-radical surgery which demands tackling significant tumour burden in pelvis, lower and upper abdomen which usually constitutes bowel resection, liver mobilisation, ancillary cholecystectomy, extensive peritonectomy, diaphragmatic resection, splenectomy, resection of enlarged pelvic, paraaortic, and rarely cardio-phrenic lymph nodes in order to achieve optimal debulking. The above can be achieved through a holistic approach to patient’s care, meticulous patient selection, and full engagement of the family. The decision needs to be carefully balanced after obtaining an informed consent, and an appreciation of the impact of such surgery on the quality of life against the survival benefit. This chapter will describe the complexity and surgical challenges in the management of advanced ovarian cancer.

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