Clinical characterization of long term survivors (LTS) in ovarian cancer (OC): Results of a propensity score matched (PSM) analysis of the international prospective tumor bank for ovarian cancer (TOC Network).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17063-e17063
Author(s):  
Elena Ioana Braicu ◽  
Hannah Woopen ◽  
Joanna Glajzer ◽  
Oliver Hunsicker ◽  
Linn Woelber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nearest Neighbor ◽  
Clonal Diversity ◽  
Residual Tumor ◽  
Figo Stage ◽  
Control Group ◽  
Tumor Spread ◽  
Clinical Appearance ◽  
Platinum Based Chemotherapy ◽  
Upper Abdomen

e17063 Background: OC has the highest mortality rate amongst gynecological malignancies. Nevertheless a small fraction of OC patients will survive longer than 8 years. Aim of our study was to analyze differences in the clinical appearance and management of LTS versus “classical” OC patients. Methods: OC patients living longer than 8 years were identified within the TOC Network between 1998 and 2008, representing the LTS subgroup. PSM analysis was used to select comparable groups of LTS and OC patients who died within first 5 years (control group - CG). PSM was conducted using nearest neighbor caliper matching without replacement to match LTS and CG for age, FIGO and residual tumor mass. All calculations were performed with the R project for Statistical Computing (R-packages used: “MatchIt”). Results: A total of 347 OC patients with different histological subtypes were included in the current analysis, i.e. 173 LTS and 174 in the CG. After PSM 114 patients remained in each group. Patients had similar age, FIGO stage and residual mass (p = 0.99, p = 0.35 and p = 0.88, respectively). Tumor spread in middle and upper abdomen (p = 0.002 and 0.013, respectively) was higher and diaphragm, mesentery and peritoneum (p = 0.009, 0.037 and 0.002, respectively) were significantly more often involved in CG than in the LTS. When only considering the HGSOC patients, 95 patients remained in each group. All patients received surgery and platinum based chemotherapy. The PSM analysis showed significant higher involvement of upper abdomen (p = 0.028), higher peritoneal spread (p = 0.002), higher ascites volume (p = 0.0007) and higher bowel resection rates (p = 0.002) in the CG compared to LTS. Neoadjuvant chemotherapy rate was similar in the LTS and CG (p = 0.5). Conclusions: Based on this PSM analysis, HGSOC-LTS seem to have mainly similar clinical pattern as the control group, however with lower rates of ascites and involvement of upper abdomen. Molecular characterization including analysis of clonal diversity might help elucidate mechanisms of tumor spread and good prognosis.

Evaluation of serial serum IL-6 levels in women with newly diagnosed ovarian cancer on a prospective clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5065-5065 ◽  
Author(s):  
J. Mahoney ◽  
H. Lee ◽  
R. Foster ◽  
U. Matulonis ◽  
Z. Duan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Data ◽  
Residual Disease ◽  
Sandwich Elisa ◽  
Stage Iv ◽  
Residual Tumor ◽  
Figo Stage ◽  
Ca 125 ◽  
Platinum Based Chemotherapy ◽  
Surgical Debulking

5065 Background: Elevated levels of IL-6 in serum have been reported in patients (pts) with mullerian malignancies (MM) and have been associated with a poor prognosis. Little is know about the behavior of IL-6 during effective cytotoxic therapy and its correlation to various clinical parameters. Methods: Pts with surgically debulked FIGO Stage II, III, and IV MM were enrolled in the Modified Triple Doublets trial. 83 pts were assigned to a cohort in accordance with the extent of surgical debulking. Cohort I included women who had been optimally cytoreduced to <1cm of residual tumor. Cohort II consisted of pts who had either post-debulking residual disease >1cm or stage IV disease. Both cohorts were treated with 3 sequential chemotherapy doublets, gemcitabine/carboplatin, paclitaxel/carboplatin, and adriamycin/topotecan. Each doublet was delivered for 3 cycles. Serum was collected from pts prior to initiating each doublet at cycles 1, 4, 7 and at the end of study (post cycle 9). Serum IL-6 levels were measured in triplicate by sandwich ELISA. Results: Pts with MM had elevated levels of IL-6 following debulking surgery (mean = 12.7 pg/ml) as compared to normal controls (n = 11, mean IL-6 = 1.5 pg/ml, p =.01). While there was no significant correlation between IL-6 levels and stage of disease, the IL-6 serum concentrations did correlate with extent of surgical debulking (p = 0.0182). IL-6 concentrations dropped throughout all cycles of platinum based treatment with post platinum treatment mean concentration of 3.9pg/ml. IL-6 levels did not correlate with outcome of second look operation and there was no statistically significant correlation between IL-6 and CA-125 levels (p = 0.1612). Survival data is still immature with a median follow-up of 34 months, yet elevation of IL-6 levels following surgery demonstrates a trend towards inferior survival. Conclusions: IL-6 levels are elevated in ovarian cancer pts following surgical debulking and correlate with the volume of residual disease following surgical cytoreduction. Values decrease during cytoreductive platinum based chemotherapy although IL-6 was not as predictive of response as was CA-125. Data demonstrates a weak correlation betweenworse survival and elevated IL-6 levels. Supported by the Lana Vento Foundation. No significant financial relationships to disclose.

Profiles of ovarian cancer patients that benefit from taxane-platinum and platinum-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16005-16005
Author(s):  
J. Markowska ◽  
M. Bidziáski ◽  
J. Stelmachów ◽  
E. Kraszewska ◽  
I. Ziółkowska-Seta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Immunohistochemical Analysis ◽  
Residual Tumor ◽  
Figo Stage ◽  
Postoperative Treatment ◽  
Clinicopathological Parameters ◽  
Logistic Regression Models ◽  
Risk Of Death ◽  
Platinum Based Chemotherapy

16005 Background: Taxane-platinum therapy (TP; regarded as more efficient than platinum-based therapy, PC) is a standard postoperative treatment of ovarian cancer patients; however, in 20 to 30% of patients the treatment is uneffective. Normal TP53 protein is a prerequisite of cancer cell response to PC, while TP53 inefficiency may enhance tumor sensitivity to taxanes. We compared the effectiveness of PC (n=253) and TP (n=199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease. Methods: Immunohistochemical analysis with PAb1801 antibody was performed on 452 archival tumors; multivariate analysis by the Cox and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)]. The therapeutic regimens were evaluated in comparison with each other and also with interactions with clinicopathological parameters. Results: TP enhanced probability of complete remission (CR, p=.05), platinum sensitivity (PS, p=.02) and longer survival (OS, p=.008) in the TP53(+) group. In the TP53(-) group TP did not show an advantage over PC in regard to CR and PS and it diminished a chance of platinum highly sensitive response (p=.04). However, in the TP53(-) group TP appeared to diminish risk of death of patients >53 yrs (p=.063). Analysis of interactions revealed that TP therapy might be more efficient in patients with: endometrioid and clear cell carcinomas, stage III disease, G2 tumors or residual tumor > 2cm. Nevertheless, in the TP53(-) group TP did not diminish risk of death of patients =53 yrs with these characteristics. Conclusions: Our results suggest that taxane-platinum therapy should be given to patients older than 53 years and to all with TP53 accumulation in their tumors. In the group of patients =53 yrs and with TP53(-) tumors (20% of patients in our study) treatment with PC may be equally or possibly more efficient than TP. No significant financial relationships to disclose.

scholarly journals Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 287-294
Author(s):  
Lindy M.J. Frielink ◽  
Brenda M. Pijlman ◽  
Nicole P.M. Ezendam ◽  
Johanna M.A. Pijnenborg
Keyword(s):  
Ovarian Cancer ◽  
Clinical Practice ◽  
Adjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Figo Stage ◽  
Selective Treatment ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Practice Methods

Background: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. Methods: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Results: Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Conclusions: Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome.

scholarly journals Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 101042831882398
Author(s):  
Susana Ramalho ◽  
Liliana AL De Angelo Andrade ◽  
Cássio Cardoso Filho ◽  
Rodrigo de Andrade Natal ◽  
Marina Pavanello ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Figo Stage ◽  
Stage I ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Discoidin Domain Receptor ◽  
Post Surgery ◽  
Platinum Based Chemotherapy ◽  
Discoidin Domain Receptor 2

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

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.

scholarly journals Lung and Intercostal Upper Abdomen Ultrasonography for Staging Patients with Ovarian Cancer: A Method Description and Feasibility Study

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 85
Author(s):  
Maciej Stukan ◽  
Antonio Bugalho ◽  
Amanika Kumar ◽  
Julita Kowalewska ◽  
Dariusz Świetlik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ultrasound Examination ◽  
Test Method ◽  
Pathological Examination ◽  
Lung Ultrasonography ◽  
Reference Standard ◽  
Method Performance ◽  
Tumor Spread ◽  
The Right ◽  
Upper Abdomen

A detailed transabdominal and transvaginal ultrasound examination, performed by an expert examiner, could render a similar diagnostic performance to computed tomography for assessing pelvic/abdominal tumor spread disease in women with epithelial ovarian cancer (EOC). This study aimed to describe and assess the feasibility of lung and intercostal upper abdomen ultrasonography as pretreatment imaging of EOC metastases of supradiaphragmatic and subdiaphragmatic areas. A preoperative ultrasound examination of consecutive patients suspected of having EOC was prospectively performed using transvaginal, transabdominal, and intercostal lung and upper abdomen ultrasonography. A surgical-pathological examination was the reference standard to ultrasonography. Among 77 patients with histologically proven EOC, supradiaphragmatic disease was detected in 13 cases: pleural effusions on the right (n = 12) and left (n = 8) sides, nodular lesions on diaphragmatic pleura (n = 9), focal lesion in lung parenchyma (n = 1), and enlarged cardiophrenic lymph nodes (n = 1). Performance (described with area under the curve) of combined transabdominal and intercostal upper abdomen ultrasonography for subdiaphragmatic areas (n = 77) included the right and left diaphragm peritoneum (0.754 and 0.575 respectively), spleen hilum (0.924), hepatic hilum (0.701), and liver and spleen parenchyma (0.993 and 1.0 respectively). It was not possible to evaluate the performance of lung ultrasonography for supradiaphragmatic disease because only some patients had this region surgically explored. Preoperative lung and intercostal upper abdomen ultrasonography performed in patients with EOC can add valuable information for supradiaphragmatic and subdiaphragmatic regions. A reliable reference standard to test method performance is an area of future research. A multidisciplinary approach to ovarian cancer utilizing lung ultrasonography may assist in clinical decision-making.

scholarly journals Hypodontia phenotype in patients with epithelial ovarian cancer

2015 ◽  
Vol 49 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Anita Fekonja ◽  
Andrej Cretnik ◽  
Danijel Zerdoner ◽  
Iztok Takac
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Figo Stage ◽  
Clinicopathological Characteristics ◽  
Control Group ◽  
Malignant Tumours ◽  
Cancer Group ◽  
Significant Difference ◽  
The University ◽  
And Control

Abstract Background. Ovarian cancer is usually diagnosed in an advanced stage and the present clinical and diagnostic molecular markers for early OC screening are insufficient. The aim of this study was to identify potential relationship between the hypodontia and epithelial ovarian cancer (EOC). Patients and methods. A retrospective study was conducted on 120 patients with EOC treated at the Department of Gynaecologic and Breast Oncology at the University Clinical Centre and 120 gynaecological healthy women (control group) of the same mean age. Women in both groups were reviewed for the presence of hypodontia and the patients with EOC also for clinicopathological characteristics of EOC according to hypodontia phenotype. Results. Hypodontia was diagnosed in 23 (19.2%) of patients with EOC and 8 (6.7%) controls (p = 0.004; odds ratio [OR] = 3.32; confidence interval [CI], 1.42-7.76). There was no statistically significant difference in patients with EOC with or without hypodontia regarding histological subtype (p = 0.220); they differed in regard to FIGO stage (p = 0.014; OR =3.26; CI, 1.23-8.64) and tumour differentiation grade (p = 0.042; OR = 3.1; CI, 1.01-9.53). Also, bilateral occurrence of EOC was more common than unilateral occurrence in women with hypodontia (p = 0.021; OR = 2.9; CI, 1.15-7.36). We also found statistically significant difference between the ovarian cancer group and control group in presence of other malignant tumours in subjects (p < 0.001). Conclusions. The results of the study suggest a statistical association between EOC and hypodontia phenotype. Hypodontia might serve as a risk factor for EOC detection.

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.

Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
H. Gabra
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.

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