Clinical relevance of VEGF-receptor status in primary ovarian cancer: A pilot study for future biomarker analyses.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5556-5556
Author(s):  
Pauline Wimberger ◽  
Issam Chebouti ◽  
Jan Dominik Kuhlmann ◽  
Rainer Kimmig ◽  
Eberhart Kuhlisch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cancer Tissue ◽  
Vegf Receptor ◽  
Antiangiogenic Treatment ◽  
Primary Ovarian Cancer

5556 Background: Antiangiogenic treatment in addition to platinum/taxane based chemotherapy was shown to improve progression-free survival in first- and second-line chemotherapy in ovarian cancer patients. Predictive markers for antiangiogenic treatment are of high interest. Therefore we investigated VEGF-receptor (VEGFR) expression as possible biomarker candidate in primary ovarian cancer tissue and its clinical impact. Methods: A total of 82 patients with primary ovarian cancer were enrolled into this study. Primary tumor tissue was analyzed for the expression of VEGFR1, VEGFR2 and VEGFR3 by immunhistochemistry. Moreover, the presence of circulating tumor cells (CTC) in the blood was detected by immunomagnetic enrichment and multiplex reverse transcriptase-polymerase chain reaction (Adnatest Ovarian Cancer, Adnagen). Disseminated tumor cells (DTC) in the BM were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and subsequent automatic detection based on staining and cytomorphology. Results: Positivity for at least one VEGFR was observed in 43% of cases. The positivity rates for VEGFR1, -2 and -3 were 34%, 17% and 27%, respectively. VEGFR-status of the primary tumor neither correlated with established clinicopathogical parameters (age, FIGO-stage, nodal status, grading, histological subtype) nor with the presence of CTC or DTC. In addition, VEGFR-status does not provide prognostic significance in regard to progression-free and overall survival (OS). Nevertheless, a trend was observed that patients, being positive for VEGFR3 at primary diagnosis, were more likely to experience suboptimal debulking (p = 0.074). CTC-positivity after adjuvant therapy significantly correlated with OS, but multivariable analysis showed only residual tumor as prognostic factor for OS. Conclusions: The VEGFR-family, albeit frequently expressed in our patient cohort, provided neither prognostic nor predictive relevance, but could probably be a predictor for debulking efficiency. The implementation of VEGFR-status into future biomarker studies should carefully be considered.

Influence of platinum-based chemotherapy on disseminated tumor cells in patients with primary ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5067-5067
Author(s):  
P. Wimberger ◽  
R. Kimmig ◽  
A. Schulte ◽  
M. E. Scheulen ◽  
S. Kasimir-Bauer
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Gradient Centrifugation ◽  
Prognostic Significance ◽  
Disseminated Tumor Cells ◽  
High Dose ◽  
Blood Samples ◽  
Primary Ovarian Cancer ◽  
Platinum Based Chemotherapy ◽  
The Impact

5067 Background: Recent studies in patients (pts) with breast cancer have demonstrated the prognostic significance of disseminated tumor cells (DTC) in the bone marrow (BM) which even can survive high-dose chemotherapy. For ovarian cancer, the impact of chemotherapy on DTC is unknown. Here we evaluated whether first-line chemotherapy with carboplatinum and paclitaxel can eliminate DTC in BM and peripheral blood (PB) of pts with primary ovarian cancer (OC, FIGO IC-IIIC). Methods: PB of 28 pts with OC and bilateral BM aspirates of 18/28 pts were assessed for DTC before and after chemotherapy using density gradient centrifugation and an immunocytochemical cytokeratin (CK) assay with the anti-CK antibody A45-B/B3. Results: We identified CK+ cells in 7/28 blood samples (25%) before therapy with a mean number of 2 cells/20 ml (range 1–3). After chemotherapy, CK+ cells were detected in 3/28 blood samples (11%) with a mean number of 9 cells/20 ml (range 1–18). In 5 out of these 7 CK+ patients prior to therapy, no CK+ cells were found after therapy, a no change and a reduction of DTC could be demonstrated in one patient each. CK+ cells were found in 10/18 BM samples (56%) before therapy with a mean number of 2 cells/9x10E6 BM cells (range 1–7) and in 8/18 BM samples (44%) after therapy with a mean number of 10 cells/9x10E6 BM cells (range 2–35). After chemotherapy, no CK+ cells were found in 6 pts, no change in DTC counts was documented in 2 pts and a significant enhancement of DTC was shown in 6 pts, including 4 pts who had no CK+ cells before chemotherapy. Conclusions: DTC are frequently present in the BM and PB of pts with OC and are not always successfully eliminated after platinum-based chemotherapy. It has to be considered, whether these pts might profit from an additive immunotherapy as already shown by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells (Proc Am Assoc Cancer Res 46: 4260, 2005). No significant financial relationships to disclose.

scholarly journals Association of a Combined Cancer Exhaustion Score with Circulating Tumor Cells and Outcome in Ovarian Cancer—A Study of the OVCAD Consortium

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5865
Author(s):  
Eva Obermayr ◽  
Elena Ioana Braicu ◽  
Stephan Polterauer ◽  
Liselore Loverix ◽  
Nicole Concin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Primary Therapy ◽  
Reactive Protein ◽  
Primary Epithelial Ovarian Cancer

We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment.

Persistence of EpCAM-positive disseminated tumor cells after platinum-based chemotherapy in the bone marrow of patients with primary ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16023-16023
Author(s):  
P. Wimberger ◽  
M. Heubner ◽  
R. Kimmig ◽  
M. E. Scheulen ◽  
S. Kasimir-Bauer
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Gradient Centrifugation ◽  
Progression Free Survival ◽  
Disseminated Tumor Cells ◽  
Rank Test ◽  
Primary Ovarian Cancer ◽  
Platinum Based Chemotherapy ◽  
The Impact

16023 Background: The impact of chemotherapy on disseminated tumor cells (DTC) in ovarian cancer is still unknown. Therefore we evaluated in 30 patients with primary ovarian cancer, undergoing radical tumor debulking surgery, (1) the influence of first-line chemotherapy with carboplatinum and paclitaxel on DTC elimination in bone marrow (BM) and peripheral blood (PB), (2) the coexpression of the epitelial antigen EpCAM on DTC and (3) the impact on progression free survival (PFS). Methods: DTC were detected in PB (20ml) and bilateral BM aspirates (10ml) using density gradient centrifugation and immunocytochemistry, applying the anti-cytokeratin antibody A45-B/B3. EpCAM-positive DTC were analyzed by using the antibodies HEA-125-FITC and Ber-EP4-FITC. PFS was estimated using the Kaplan-Meier method and statistically evaluated using a two-sided log-rank test. A significant increase or decrease of DTC was assessed if the difference was = 2 DTC. Results: Before chemotherapy, we identified DTC in 16% of PB samples with a mean number of 2 cells (range 1–3) and in 50% of BM samples with a mean number of 3 cells/9x10E6 BM cells (range 1–8). After chemotherapy, DTC were detected in PB in only one patient but still in 50% of BM samples with a with a mean number of 17 cells/9x10E6 BM cells (range 1–100). In BM, chemotherapy completely eliminated DTC in 30% of the patients, no significant change was documented in 47% and a significant enhancement of DTC was shown in 33%, including 8 patients (27%) who had no DTC before chemotherapy. In case of significant increase of DTC, patients showed a trend for reduced PFS (12.8 months ± 0.7; mean PFS ± SEM) in comparison to patients with no increase (19.3 months ± 1.4) or decrease of DTC (p=0.07). DTC, persisting after chemotherapy, co-expressed EpCAM. Conclusions: It has to be considered, whether these patients with persisting EpCAM-positive DTC in BM might profit from an additive immunotherapy e.g. by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells. No significant financial relationships to disclose.

scholarly journals To assess the role of addition of bevacizumab therapy to carboplatin and paclitaxel as frontline treatment of epithelial ovarian cancer

2016 ◽  
Author(s):  
Richa Vatsa ◽  
Sunesh Kumar ◽  
Lalit Kumar
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Safety Profile ◽  
Haematological Toxicity ◽  
Progression Free Survival ◽  
New Drugs ◽  
Secondary Outcome ◽  
Vegf Receptor ◽  
Persistent Proteinuria

Introduction: Efforts are going on for development of new drugs for epithelial ovarian cancer (EOC). We assessed safety profile of bevacizumab, a VEGF receptor blocking antibody in treatment of EOC. Methods: We assigned women with EOC to carboplatin (area under curve, 5 or 6) and paclitaxel (175 mg/square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (15 mg/kilogram body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 30 additional cycles. Primary outcome measures was safety profile of bevacizumab and secondary outcome was to see progression free survival (PFS). Results: Out of 30 patients, 10 were in Bevacizuma arm (Arm A) and 20 in conventional chemotherapy arm (Arm B). Haematological toxicity, GI perforation and proteinuria was similar in both. Other toxicities e.g. bleeding complication (p = 0.002) and hypertension (p = 0.04) was more in Arm A. PFS was similar in both arms; 24 months in Arm A and 22 months in Arm B (p = 0.565). 4 (40%) patients in arm A discontinued treatment, two (20%) because of disease progression after PFS of 9 and 6 months, two because of development of toxicity considered to be due to bevacizumab; of which one developed jejenal perforation and disease progression after PFS of 6 months and 1 because of development of persistent proteinuria of grade 3 after 18 months. Conclusion: Bevacizumab therapy does not improve PFS in EOC but increases toxicity spectrum of chemotherapy.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

Prospective study with circulating tumor cells as potential prognosis biomarker in metastatic colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 203-203 ◽  
Author(s):  
Virgilio Souza E Silva ◽  
Emne Ali Abdallah ◽  
Celso Abdon Lopes de Mello ◽  
Milena Shizue Tariki ◽  
Vinicius Fernando Calsavara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prospective Study ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Blood Collection ◽  
Multidrug Resistance Protein 1 ◽  
Promising Tool ◽  
The Right

203 Background: Colorectal cancer (CRC) is one of the most common cancer worldwide. Around 30% present metastatic disease at diagnosis and 50%–60% of patients develop metastasis. New prognostic markers are needed and circulating tumor cells (CTCs) are a promising tool. Methods: Prospective study conducted by blood collection from 75 patients (pts) with metastatic CRC (mCRC), twice, with 2 months interval, together with image exams for therapeutic response evaluation. CTCs were detected by ISET and identified by immunocytochemistry. Results: The mean age was 57.3 years old (24-81). RAS mutations in primary tumor was found in 38% (19/50) of patients (pts) and left colon topography in 41.3% (31/75). Comparing the baseline CTC level (CTC1) with the level at first follow-up (CTC 2), pts with CTC2 – CTC1 > 5.5 per ml demonstrated poor progression-free survival (PFS) (3.2 months) when compared to CTC 2 – CTC1 ≤ 5.5 (9.1 months) (p= 0.005). The median overall survival (OS) was 24.5 months for pts with CTC 1 > 1.5 per ml and 34.2 months for those with CTC1 ≤ 1.5 per (HR=1.89, 95% CI, 1.01 to 3.52; p= 0.041). Patients with RAS mutation (P= 0.001), primary tumor in the right colon (p= 0.014) and expression of Multidrug Resistance Protein 1 in CTCs (p= 0.044) had worse OS. By multivariable analyses, CTC 1 > 1.5/mL (p= 0.025) was an independent prognostic factor. Conclusions: This prospective study confirmed that counts of CTCs at baseline (CTC1) is an important prognostic marker for monitoring mCRC and correlates with other established prognostic factors. Clinical trial information: NCT02979470.

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

2017 ◽  
Vol 27 (9) ◽  
pp. 1850-1855 ◽  
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.

Circulating Tumor Cells As Prognostic Markers in Neuroendocrine Tumors

2013 ◽  
Vol 31 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Mohid S. Khan ◽  
Amy Kirkwood ◽  
Theodora Tsigani ◽  
Jorge Garcia-Hernandez ◽  
John A. Hartley ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Immunomagnetic Separation ◽  
Tumor Burden

Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells. Results Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.

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