A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer

AbstractThe best prognosis for advanced ovarian cancer is provided by no residual disease after primary cytoreductive surgery. It is thus important to be able to predict resectability that will result in complete cytoreduction, while avoiding unnecessary surgery that may leave residual disease. No single procedure appears to be sufficiently accurate and reliable to predict resectability. The process should include a preoperative workup based on clinical examination, biomarkers, especially tumor markers, and imaging, for which computed tomography, as well as sonography, magnetic resonance imaging and positron-emission tomography, can be used. This workup should provide sufficient information to determine whether complete cytoreduction is possible or if not, to propose neoadjuvant chemotherapy which is preferable in this case. For the remaining patients, laparoscopy is broadly recommended as an ultimate triage step. However, its modalities are still debated, and several scores have been proposed for standardization and improving accuracy. The risk of false negatives requires a final assessment of resectability as the first stage of cytoreductive surgery by laparotomy. Composite models, consisting of several criteria of workup and, sometimes, laparoscopy have been proposed to improve the accuracy of the predictive process. Regardless of the modality, the process appears to be accurate and reliable for predicting residual disease but less so for predicting complete cytoreduction and thus avoiding unnecessary surgery and an inappropriate treatment strategy. Overall, the proposed procedures are heterogeneous, sometimes unvalidated, or do not consider advances in surgery. Future techniques and/or models are still needed to improve the prediction of complete resectability.

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The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001107 ◽

2017 ◽

Vol 27 (9) ◽

pp. 1850-1855 ◽

Cited By ~ 4

Author(s):

Takahiro Ebata ◽

Mayu Yunokawa ◽

Hiroshi Yoshida ◽

Seiko Bun ◽

Tatsunori Shimoi ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factors ◽

Tumor Cells ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Complete Response ◽

Pathological Response ◽

Prognostic Impact ◽

Grade 3 ◽

Dose Dense

ObjectiveThe aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy.MethodsWe retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen.ResultsSixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2–6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26–0.92).ConclusionsAlthough the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.

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Impact of Complete Cytoreduction Leaving No Gross Residual Disease Associated with Radical Cytoreductive Surgical Procedures on Survival in Advanced Ovarian Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-012-2446-8 ◽

2012 ◽

Vol 19 (13) ◽

pp. 4059-4067 ◽

Cited By ~ 93

Author(s):

Suk-Joon Chang ◽

Robert E. Bristow ◽

Hee-Sug Ryu

Keyword(s):

Ovarian Cancer ◽

Surgical Procedures ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Complete Cytoreduction

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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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5514 ◽

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.

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Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920967241 ◽

2020 ◽

Vol 12 ◽

pp. 175883592096724

Author(s):

Jiatao Hao ◽

Hui Yu ◽

Taohong Zhang ◽

Ruifang An ◽

Yan Xue

Keyword(s):

Systematic Review ◽

Ovarian Cancer ◽

Multivariate Analysis ◽

Meta Analysis ◽

Tumor Infiltrating Lymphocytes ◽

Extensive Literature ◽

Prognostic Impact ◽

High Grade ◽

Serous Ovarian Cancer ◽

Infiltrating Lymphocytes

Background: Tumor-infiltrating lymphocytes (TILs) are involved in the antitumor immune response. The association between prognosis in patients with TILs and high-grade serous ovarian cancer (HGSOC) remains obscure, with some studies reporting conflicting results. Methods: We conducted an extensive literature search of electronic databases and retrieved prognostic data of each selected subtype of TILs, including CD3+, CD4+, CD8+, CD103+, and PD-1+ TILs. The fixed-effects model was applied to derive the pooled hazard ratio (HR) and 95% confidence interval (CI) of these markers. Results: The systematic review process yielded 19 eligible studies comprising 6004 patients with HGSOC. We compared TIL-positive and TIL-negative patients, and the pooled HRs from the multivariate analysis revealed that intraepithelial CD8+ TILs were positively correlated with progression-free survival (PFS, HR 0.46, 95% CI 0.25–0.67) and overall survival (OS, HR 0.90, 95% CI 0.86–0.9); stromal CD8+ TILs were positively correlated with OS (HR 0.61, 95% CI 0.36–0.87). Furthermore, the pooled HRs from univariate analysis demonstrated that intraepithelial CD3+, CD4+, CD8+, and CD103+ TILs were positively associated with OS (HR 0.58, 95% CI 0.44–0.72; HR 0.37, 95% CI 0.16–0.59; HR 0.51, 95% CI 0.42–0.60, and HR 0.59, 95% CI 0.44–0.74, respectively); stromal CD4+ and CD8+ TILs were significantly associated with OS (HR 0.63, 95% CI 0.32–0.94 and HR 0.78, 95% CI 0.58–0.97, respectively). However, the pooled HR from the multivariate analysis revealed that PD-1+ TILs were not associated with the OS of patients with HGSOC (HR 0.97, 95% CI 0.90–1.04). Conclusion: This meta-analysis provided evidence of the association of CD3+, CD4+, CD8+, and CD103+ TILs with the survival benefits (OS and PFS) of patients with HGSOC.

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Prognostic impact of celiac lymph node involvement in patients after frontline treatment for advanced ovarian cancer

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2019.02.018 ◽

2019 ◽

Vol 45 (8) ◽

pp. 1410-1416 ◽

Cited By ~ 1

Author(s):

Martina Aida Angeles ◽

Gwénaël Ferron ◽

Bastien Cabarrou ◽

Gisèle Balague ◽

Carlos Martínez-Gómez ◽

...

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Advanced Ovarian Cancer ◽

Lymph Node Involvement ◽

Prognostic Impact ◽

Frontline Treatment ◽

Node Involvement

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What Should We Expect After a Complete Cytoreduction at the Time of Interval or Primary Debulking Surgery in Advanced Ovarian Cancer?

Annals of Surgical Oncology ◽

10.1245/s10434-015-5051-9 ◽

2015 ◽

Vol 23 (5) ◽

pp. 1666-1673 ◽

Cited By ~ 28

Author(s):

Luis Chiva ◽

Fernando Lapuente ◽

Teresa Castellanos ◽

Sonsoles Alonso ◽

Antonio Gonzalez-Martin

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

Complete Cytoreduction ◽

Debulking Surgery ◽

Primary Debulking Surgery

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Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Undergoing Platinum/Paclitaxel–Containing First-Line Chemotherapy: An Exploratory Analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2008.16.1109 ◽

2008 ◽

Vol 26 (16) ◽

pp. 2683-2689 ◽

Cited By ~ 53

Author(s):

Christina Fotopoulou ◽

Andreas duBois ◽

Alexandros N. Karavas ◽

Ralf Trappe ◽

Behnaz Aminossadati ◽

...

Keyword(s):

Ovarian Cancer ◽

Multivariate Analysis ◽

Venous Thromboembolism ◽

Univariate Analysis ◽

Prognostic Significance ◽

Study Group ◽

Prognostic Impact ◽

Cox Regression Analysis ◽

Cancer Study ◽

Cancer Study Group

Purpose Venous thromboembolism (VTE) has been associated with negative prognosis in cancer patients. Most series reporting on VTE have included different tumor types not differentiating between recurrent or primary disease. Data regarding the actual impact of VTE on primary advanced ovarian cancer (AOC) are limited. Patients and Methods Between 1995 and 2002, the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study group (AGO–OVAR) recruited 2,743 patients with AOC in three prospectively randomized trials on platinum paclitaxel-based chemotherapy after primary surgery. Pooled data analysis was performed to evaluate incidence, predictors, and prognostic impact of VTE in AOC. Survival curves were calculated for the VTE incidence. Univariate analysis and Cox regression analysis were performed to identify independent predictors of VTE and mortality. Results Seventy-six VTE episodes were identified, which occurred during six to 11 cycles of adjuvant chemotherapy; 50% of them occurred within 2 months postoperatively. Multivariate analysis identified body mass index higher than 30 kg/m2 and increasing age as independent predictors of VTE. International Federation of Gynecology and Obstetrics stage and surgical radicality did not affect incidence. Overall survival was significantly reduced in patients with VTE (median, 29.8 v 36.2 months; P = .03). Multivariate analysis identified pulmonary embolism (PE), but not deep vein thrombosis alone, to be of prognostic significance. In addition, VTE was not identified to significantly affect progression-free survival. Conclusion Patients with AOC have their highest VTE risk within the first 2 months after radical surgery. Only VTE complicated by symptomatic PE have been identified to have a negative impact on survival. Studies evaluating the role of prophylactic anticoagulation during this high risk postoperative period are warranted.

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