scholarly journals Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer

2020 ◽  
Author(s):  
Zhe Li ◽  
Ran An ◽  
Wendy M. Swetzig ◽  
Margaux Kanis ◽  
Nkechiyere Nwani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Outcomes ◽  
Metastatic Tumor ◽  
Tissue Response ◽  
Infrared Light ◽  
Tumor Biopsy ◽  
Tumor Tissues ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy

AbstractDevelopment of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measured in vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88% to 91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.

scholarly journals Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhe Li ◽  
Ran An ◽  
Wendy M. Swetzig ◽  
Margaux Kanis ◽  
Nkechiyere Nwani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Outcomes ◽  
Metastatic Tumor ◽  
Tissue Response ◽  
Infrared Light ◽  
Tumor Biopsy ◽  
Tumor Tissues ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy

Abstract Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measured in vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88–91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.

Prediction of survival in patients with epithelial ovarian cancer based on the timing and rate of normalization of CA125 levels during primary chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5585-5585
Author(s):  
K. S. Matthews ◽  
R. P. Rocconi ◽  
M. Kemper ◽  
K. E. Hoskins ◽  
W. K. Huh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Eligible Patient ◽  
Primary Chemotherapy ◽  
Rank Test ◽  
Primary Therapy ◽  
Linear Regression Models ◽  
Platinum Sensitivity ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy

5585 Objective: CA125 is the tumor marker used to evaluate response to chemotherapy in patients with epithelial ovarian cancer (EOC). The aim of this study was to determine if the timing of normalization or percent decrease in CA125 levels during primary chemotherapy could predict survival. Methods: Patients treated at our institution for EOC with primary taxane/platinum-based chemotherapy for 6 cycles between 1996 and 2005 were eligible. Patient demographics, chemotherapy administration, CA125 levels, and survival outcomes were abstracted. Progression-free- survival (PFS), overall survival (OS), and platinum sensitivity (> 6 months from chemotherapy completion) were compared to CA125 levels during primary therapy. Baseline levels, change over time, and timing of CA125 normalization were calculated. Analyses were performed using Kaplan-Meier method and compared using the log-rank test, Chi-square test and Fischer’s exact test. Results: 269 patients with EOC were identified. When stratified by which cycle of chemotherapy achieved normalization, PFS ranged from 25 months at 1st cycle to 4 months at 6th cycle (p< 0.001). OS showed a similar benefit from 74 months at 1st cycle to 22 months at 6th cycle (p<0.001). Platinum sensitivity improved from 23% (normal CA125 after 6th cycle) to 72% (normal CA125 after 1st cycle) (p=0.003). Patients with normalization after the 3rd cycle or sooner compared to patients with normalization after the 4th cycle demonstrated improved PFS (19 vs. 6 months; p<0.001), OS (48 vs. 27 months; p=0.001) and platinum sensitivity (78 vs. 22%; p<0.001). Linear regression models of the slope of the decline of CA125 levels correlated with PFS (p=0.03); however, the models failed to predict an OS advantage. Conclusion: Earlier normalization of CA125 levels during primary chemotherapy for EOC predicts improvement in platinum sensitivity, PFS, and OS. This data provides prognostic information that may influence future decisions regarding chemotherapy. No significant financial relationships to disclose.

Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5568-5568
Author(s):  
K. D. Steffensen ◽  
M. Waldstrøm ◽  
U. Jeppesen ◽  
I. Brandslund ◽  
A. Jakobsen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Epithelial Ovarian Cancer ◽  
Dna Adducts ◽  
Excision Repair ◽  
Snp Genotyping ◽  
Repair Capacity ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Ercc1 Expression

5568 Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross-complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum-based chemotherapy, and conversely, polymorphisms within encoding DNA repair enzymes or low repair capacity may confer sensitivity. A common single nucleotide polymorphism (SNP) of ERCC1 at codon 118 have been proposed to impair ERCC1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum based chemotherapy. The aim of this study was to evaluate ERCC1 expression and ERCC1 118 polymorphism in epithelial ovarian cancer and the potential association with response to platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tissue sections from 159 patients with epithelial ovarian cancer, FIGO stage IIb-IV, were used for immunohistochemistry (monoclonal mouse antibody, clone 8F1, Neomarkers). ERCC1 codon 118 SNP genotyping was performed by real time PCR, Taqman SNP genotyping assay. Results: ERCC1 protein overexpression was found in 37.7 % of the tumors. The response rate (normalization of CA125 during platinum-based chemotherapy) was 63.6 % (35/55) in patients with ERCC1-negative tumors compared to only 35.6 % (16/45) in patients with ERCC1-positive tumors. (p = 0.0052, χ2). Furthermore increasing immunohistochemical score (H-score) was associated with poorer response to chemotherapy. (p = 0.0006, Spearman`s). The T/T genotype (44 %) showed better response to chemotherapy than C/C + C/T (15 % + 41 %) variants (p=0.042). Conclusions: Patients with ERCC1-negative tumors appear to have significantly better response to platinumbased chemotherapy compared to patients with ERCC1-positive tumors. In addition the TT genotype seems to be favorable towards better response to platinum-based chemotherapy. No significant financial relationships to disclose.

scholarly journals Treatment of Recurrent Epithelial Ovarian Cancer

2020 ◽  
Vol 80 (12) ◽  
pp. 1195-1204
Author(s):  
Carlota Claussen ◽  
Achim Rody ◽  
Lars Hanker
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Epithelial Ovarian Cancer ◽  
Tumor Biology ◽  
Advanced Ovarian Cancer ◽  
Parp Inhibitors ◽  
Free Interval ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
New Findings

AbstractEpithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding first-line therapy, making further lines of therapy necessary. The choice of therapy depends on various criteria such as tumor biology, the patientʼs general condition (ECOG), toxicity, previous chemotherapy, and response to chemotherapy. The platinum-free or treatment-free interval determines the potential response to repeat platinum-based therapy. If patients have late recurrence, i.e. > 6 months after the end of the last platinum-based therapy (i.e., they were previously platinum-sensitive), then they are usually considered suitable for another round of a platinum-based combination therapy. Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD. While the use of surgery to treat recurrence has long been a controversial issue, new findings from the DESKTOP III study of the AGO working group have drawn attention to this issue again, particularly for patients with a platinum-free interval of > 6 months and a positive AGO score. Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib. These drugs have substantially changed current treatment practice and expanded the range of available therapies. It is important to differentiate between purely maintenance therapy after completing CTX, continuous maintenance therapy during CTX, and the therapeutic use of these substances. The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.

scholarly journals The impact of EpCAM expression on response to chemotherapy and clinical outcomes in patients with epithelial ovarian cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (27) ◽  
pp. 44312-44325 ◽  
Author(s):  
Shingo Tayama ◽  
Takeshi Motohara ◽  
Dashdemberel Narantuya ◽  
Chenyan Li ◽  
Koichi Fujimoto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Outcomes ◽  
Epcam Expression ◽  
Response To Chemotherapy ◽  
The Impact

Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

2004 ◽  
Vol 22 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Viviane Hess ◽  
Roger A'Hern ◽  
Nazar Nasiri ◽  
D. Michael King ◽  
Peter R. Blake ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
Controlled Study ◽  
First Line ◽  
Gynecology And Obstetrics ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Histologic Subtypes

Purpose Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. Patients and Methods Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. Results Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P = .01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P = .009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P < .001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P < .001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P < .001) and 3.08 (95% CI, 1.69 to 5.6; P < .001), respectively, for mEOC patients as compared with controls. Conclusion Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Clinical outcomes of patients with endometrioid epithelial ovarian cancer following surgical treatment

2021 ◽  
Author(s):  
Paulina Cybulska ◽  
Jill Tseng ◽  
Qin C. Zhou ◽  
Alexia Iasonos ◽  
Deborah F. Delair ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Surgical Treatment ◽  
Epithelial Ovarian Cancer ◽  
Clinical Outcomes

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

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.

Sign in / Sign up

Export Citation Format

Share Document