Impact of Extended Primary Surgery on Suboptimally Operable Patients With Advanced Ovarian Cancer

2016 ◽  
Vol 26 (5) ◽  
pp. 873-883 ◽  
Author(s):  
Anton Oseledchyk ◽  
Lena Elisa Hunold ◽  
Michael R. Mallmann ◽  
Christian M. Domröse ◽  
Alina Abramian ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Complication Rates ◽  
Oncologic Surgery ◽  
Primary Surgery ◽  
Optimal Debulking ◽  
Upper Abdomen ◽  
Extensive Surgery

ObjectivesExtensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today’s criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions.MethodsAll patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study.ResultsFifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates.ConclusionsBecause of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.

Prognostic impact of the time interval between primary surgery and start of first-line chemotherapy in patients with advanced ovarian cancer: Analysis of prospective randomized phase III trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5514-5514
Author(s):  
S. Mahner ◽  
A. Staehle ◽  
C. zu Eulenburg ◽  
K. Wegscheider ◽  
A. Reuss ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Phase Iii ◽  
Time Interval ◽  
Prognostic Impact ◽  
First Line ◽  
Primary Surgery ◽  
Line Chemotherapy

5514 Background: Primary surgery followed by platinum-taxane chemotherapy is the standard therapy of advanced ovarian cancer. It is not clear, whether the time interval between surgery and start of first line chemotherapy (time to chemo - TTC) has an impact on the clinical outcome. Methods: Individual patient data meta-analysis of three prospective randomized AGO-OVAR/GINECO trials (AGO OVAR 3, 5, and 7) conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Cox proportional hazard models were applied to evaluate the prognostic impact of different variables on survival; TTC was introduced as a continuous variable. Results: A total of 3,326 patients were analyzed. Chemotherapy was started within 8 weeks after surgery. Median progression-free survival (PFS) was 17.91 months (95% CI: 17.15–18.73 months) and median overall survival (OS) 37.83 months (95% CI: 36.57–38.90 months). The median TTC was 19 days (95% CI: 18–19 days, range 1–56 days). By multivariate analysis of the total cohort, there was no significant association between TTC and PFS (p = 0.131) or OS (p = 0.372). In the subgroup of patients with no residual tumor after debulking surgery (n = 1.101), a significant and independent correlation between early start of chemotherapy and improved overall survival was observed (p = 0.022). Conclusions: Our analysis represents the largest study investigating treatment delivery and outcome in ovarian cancer. The time interval between primary surgery and start of first line chemotherapy seems to have no general impact in all patients. However, it could be demonstrated for the first time that a delayed start of chemotherapy was independently associated with decreased overall survival in patients with complete surgical debulking. As previously shown for other biological factors in ovarian cancer, the presence of residual tumor after surgery seems to prevail over the prognostic impact of therapy initiation. No significant financial relationships to disclose.

Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10093-10093
Author(s):  
A. Reinthaller ◽  
P. Sevelda ◽  
L. A. Hefler
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Tumor Grade ◽  
Residual Tumor ◽  
Figo Stage ◽  
Tumor Mass ◽  
Prognostic Parameter ◽  
Primary Surgery ◽  
Preoperative Serum ◽  
Residual Tumor Mass

10093 Objective: Serum vascular endothelial growth factor (VEGF) levels have been shown to be associated with an adverse outcome in patients with ovarian cancer. We studied the clinical value of serum VEGF as an independent prognostic parameter. Methods: In the present study, we ascertained preoperative serum VEGF in a series of 314 patients with ovarian cancer. VEGF serum were evaluated in 45 new cases. Serum VEGF was evaluated prior to primary surgery in all patients. The re-analysis of previously published data comprised a total of 269 cases. Patients were treated between 1990 and 2003. Mean duration of follow-up was 38.9 (32.4) months. Patients with epithelial ovarian cancer were included into the present study, patients with other malignant ovarian tumors, borderline tumors, and benign adnexal masses were excluded. Serum VEGF was evaluated prior to primary surgery using an enzyme linked immunosorbent assay (Quantikine Human VEGF Immunoassay; R&D Systems, Minneapolis, MN) in all studies. Results were correlated with clinical data. Results: Median serum VEGF was 407 (238–746) pg/mL. Serum VEGF was associated with serum CA 125 (p=0.003) and residual tumor mass (p=0.02; residual tumor mass < 1cm: 375.5 [209.5–608.9] pg/mL vs. residual tumor mass ≥ 1cm: 625.2 [320.7–1046.7] pg/mL). Serum VEGF was not associated with FIGO stage (p=0.5), lymph node involvement (p=0.2), tumor grade (p=0.2), and patients’ age (p=0.08). In a univariate Kaplan-Meier analysis, FIGO stage, residual tumor mass, tumor grade, patients’ age, serum CA 125, and preoperative serum VEGF were associated with overall survival. In a multivariate Cox regression model, higher FIGO stage, presence of residual tumor mass after primary surgery, and higher serum VEGF were independently associated with a shortened overall survival. Planned subgroup analysis was performed for patients with ovarian cancer FIGO stage I. In a multivariate Cox regression model, higher tumor grade and higher serum VEGF were the only independent prognosticators for overall survival. Patients with FIGO stage I ovarian cancer and a serum VEGF ≥ 380 pg/mL had a 8-fold increased risk for experiencing cancer related death. Conclusion: Serum VEGF is an independent prognostic parameter in patients with all stages of ovarian cancer. No significant financial relationships to disclose.

Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18066-e18066
Author(s):  
Alexey Rumyantsev ◽  
Alexandra Tyulyandina ◽  
Ilya Pokataev ◽  
Konstantin Morkhov ◽  
Valentina Mikhailovna Nechuskina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Severe Neutropenia ◽  
Front Line ◽  
Debulking Surgery ◽  
Dose Dense ◽  
Optimal Debulking

e18066 Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size > 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.

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.

Phase II Feasibility Study of Sequential Couplets of Cisplatin/Topotecan Followed by Paclitaxel/Cisplatin as Primary Treatment for Advanced Epithelial Ovarian Cancer: A National Cancer Institute of Canada Clinical Trials Group Study

2000 ◽  
Vol 18 (24) ◽  
pp. 4038-4044 ◽  
Author(s):  
P. Hoskins ◽  
E. Eisenhauer ◽  
I. Vergote ◽  
J. Dubuc-Lissoir ◽  
B. Fisher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
Primary Treatment ◽  
Ca 125 ◽  
Debulking Surgery ◽  
Primary Surgery ◽  
Nonhematologic Toxicity ◽  
Interval Debulking Surgery ◽  
Optimal Debulking

PURPOSE: Despite the improved results in advanced ovarian cancer achieved with the addition of paclitaxel to frontline therapy, there remains room for improvement. One approach is to add new agents such as topotecan. Because myelosuppression limits the delivery of topotecan with paclitaxel/cisplatin in a three-drug combination, we explored giving sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin. PATIENTS AND METHODS: Forty-four patients with residual epithelial ovarian carcinoma after primary surgery were studied. Cisplatin 50 mg/m2 on day 1 and topotecan 0.75 mg/m2 on days 1 through 5 were administered at 21-day intervals for four cycles, followed by interval debulking surgery (if optimal debulking was not achieved with primary surgery), and then paclitaxel 135 mg/m2 over 24 hours on day 1 and cisplatin 75 mg/m2 on day 2 at 21-day intervals for four cycles. RESULTS: Such sequential couplets are feasible. Myelotoxicity was the major toxic effect, but it was of short duration. The granulocyte nadir with topotecan/cisplatin occurred late (median, day 18), so retreatment on day 21 was not always possible. There was no unexpected nonhematologic toxicity. The regimen was active in this group of patients who had undergone largely suboptimal debulking surgery. In 34 patients with clinically measurable disease, the overall response rate was 78%, and 30 (77%) of the 39 patients with elevated CA 125 levels at baseline had normalization of CA 125 levels by the end of therapy. CONCLUSION: Sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin are feasible. The efficacy data in this suboptimal group of patients has encouraged us to proceed with a randomized study based on this approach.

The Role of Induction Chemotherapy in Inoperable Ovarian Cancer

1989 ◽  
Vol 75 (6) ◽  
pp. 609-614 ◽  
Author(s):  
Michela Donadio ◽  
Gianmaria Bonardi ◽  
Valter Iberti ◽  
Oscar Bertetto ◽  
Flavio Carnino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Induction Chemotherapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Optimal Debulking

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR+PR was observed in 24/30 (80 %) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1 %) patients had a complete macroscopic resection; 9/24 (37.5 %) patients had a partial resection (residual tumor <2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28 %. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study

2021 ◽  
pp. ijgc-2021-002434
Author(s):  
Gennaro Daniele ◽  
Francesco Raspagliesi ◽  
Giovanni Scambia ◽  
Carmela Pisano ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Line Treatment ◽  
First Line ◽  
Primary Surgery ◽  
First Line Treatment

ObjectiveTo explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab.MethodsA multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints.ResultsFrom October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1–40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported.ConclusionsEfficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors.Trial registration numberEudraCT 2012-003043-29; NCT01706120.

scholarly journals The Relationship Between Retroperitoneal Lymphadenectomy and Survival in Advanced Ovarian Cancer Patients

2019 ◽  
Author(s):  
Ping Zhang ◽  
Chenyan Fang ◽  
Yingli Zhang ◽  
Lingqin Zhao ◽  
Xi Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Postoperative Complications ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Retroperitoneal Lymphadenectomy ◽  
Free Survival

Abstract Background Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients; nevertheless, the effect remains controversial. Thus, the current study was carried out aiming to evaluate the benefit of systematic retroperitoneal lymphadenectomy in such patients with optimal cytoreduction. Methods Patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally debulked (residual tumor <1 cm or absent) and divided into two groups. Group A (n =170) (no-lymphadenectomy group): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n=240): patients underwent systematic retroperitoneal lymphadenectomy. Results A total of 410 eligible patients were enrolled in the analysis. The median age was 51 years (range: 28–72). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78% and 24% in the no-lymphadenectomy group and 76% and 26% in the lymphadenectomy group (P=0.385 and P=0.214, respectively). Subsequently, there was no significant difference in 5-year overall survival and 2-year progression-free survival between the two groups stratified to histological type (serous or non-serous type), the clinical evaluation for lymph nodes (negative) or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor affecting survival of patients. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P=0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]). Conclusions Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival in advanced ovarian cancer patients with residual tumor <1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.

TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7)

2019 ◽  
Vol 29 (8) ◽  
pp. 1327-1331 ◽  
Author(s):  
Alexander Reuss ◽  
Andreas du Bois ◽  
Philipp Harter ◽  
Christina Fotopoulou ◽  
Jalid Sehouli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Complete Resection ◽  
Peritoneal Carcinoma ◽  
Exclusion Criteria ◽  
Platinum Based Chemotherapy

BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.Primary ObjectiveTo clarify the optimal timing of surgical therapy in advanced ovarian cancer.Study HypothesisPrimary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.Trial DesignTRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.Major Inclusion/Exclusion CriteriaMajor inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.Primary EndpointOverall survival.Sample Size772 patients.Estimated Dates for Completing Accrual and Presenting ResultsAccrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.Trial RegistrationNCT02828618.

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