Measurement of the Ovarian Cancer-Associated Antigen CA 125 in Monitoring Tumor Burden and Response to Chemotherapy

Two human monoclonal antibodies, HID-7E7 and ROB-6F2, were produced by EBV transformation of peripheral blood lymphocytes (PBL). PBL were obtained from a patient with ovarian cancer who had been exposed several times to a Tc-99m labeled murine monoclonal anti-CA 125 antibody (B43.13, Biomira, Edmonton) for immunoscintigraphy. The HID-7E7 and ROB-6F2 producing B-cells were cloned with a limiting dilution technique and have shown stable immunoglobulin secretion within a period of three years. The human monoclonal antibodies HID-7E7 and ROB-6F2 are of the IgG isotype, and bind with significant affinity to the murine monoclonal antibody B43.13, which was used for immunoscintigraphy. Binding affinity of ROB-6F2 to other murine antibodies could not be detected. Cross reactivity of HID-7E7 to a murine anti-CEA monoclonal antibody was observed. In order to verify the anti-idiotypic character of the generated human antibodies, the ability of HID-7E7 and ROB-6F2, respectively, to inhibit the formation of the CA125/B43.13 complex is demonstrated via an enzyme-linked immunosorbent assay. These human anti-idiotypic antibodies are possible candidates for immunotherapy of ovarian cancer in patients with a small tumor burden following surgery and/or chemotherapy.

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Is there a CA-125 level that predicts negative second look surgery (SLS) in patients with advanced epithelail ovarian cancer (EOC)?

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.15042 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 15042-15042

Author(s):

S. Sharma ◽

P. Singhal ◽

K. Odunsi ◽

S. Lele

Keyword(s):

Ovarian Cancer ◽

Disease Free Survival ◽

Disease Status ◽

Primary Treatment ◽

Ca 125 ◽

Primary Therapy ◽

Second Look ◽

Kaplan Meier ◽

Response To Chemotherapy ◽

Disease Free

15042 Background: The value of second look surgery (SLS) in advanced epithelial ovarian cancer (EOC) has been has been questioned because performing this procedure has not been associated with a clear survival advantage.However, SLS continues to be the most accurate means of documenting the response to chemotherapy, and therfore still used in investigational protocols. The primary purpose of this study was to assess the levels of CA 125 after treatment, that could predict absence of disease at SLS. Methods: Between 1998 and 2003, 98 stage III EOC patients who underwent optimal cytoreductive surgery, completed 6 cycles of platinum/paclitaxel chemotherapy, and were NED (no evidence of disease: normal CA 125, normal physical and radiological examination) were included in this study. SLS was performed at 6–8 weeks from completion of primary therapy. Patients with disease present at SLS were considered to have persistent disease and received second line chemotherapy. Patient demographics, surgical and chemotherapy treatments, and CA 125 levels prior to start and at completion of primary treatment were collected retrospectively. Survival was estimated by the Kaplan-Meier method. Results: Forty seven out of 98 (48%) of optimally debulked patients who were NED at completion of primary therapy underwent SLS. Twenty-five out of 47 patients (53%) had evidence of disease at SLS and 22 out of 47 patients (47%) were NED at SLS. The median disease free survival was 42 months (95% CI 16, 81) in patients with negative SLS compared with 17 months (95% CI 9, 45) in patients who did not undergo SLS (p = 0.03). Estimated 5-year survival in patients with negative SLS was 90% compared to 50% in patients who did not undergo SLS (p = 0.05). CA 125 levels of ≤ 10 after completion of primary therapy was predictive of negative SLS (p < 0.05). Conclusions: SLS evaluation of disease status appears to be a more accurate than standard clinical evaluation in patients who are NED at completion of their primary therapy. Negative SLS also appears to be a predictor of improved disease free and overall survival. Furthermore, CA 125 ≤ 10 is predictive of negative SLS in patients who are NED after completion of primary therapy. No significant financial relationships to disclose.

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The relevance of rising CA-125 levels within the normal range in predicting recurrence in patients with advanced stage ovarian cancer: A validation study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16521 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16521-e16521

Author(s):

F. AbuShain ◽

P. Escobar ◽

S. Shahabi ◽

C. Michener ◽

R. Drake ◽

...

Keyword(s):

Ovarian Cancer ◽

Stage Iv ◽

Complete Response ◽

Disease Recurrence ◽

Ca 125 ◽

Normal Range ◽

Number Of Patients ◽

Response To Chemotherapy ◽

Significant Difference

e16521 Background: Small published series suggested that three progressively rising CA-125 values, doubling of CA-125, and an absolute rise of 5 U/mL from the nadir, all while remaining in the normal range were highly associated with disease recurrence. This study aims to validate these proposed criteria in a larger population. Methods: We conducted a retrospective review of the records of patients with stages IIIC and IV epithelial ovarian cancer treated with primary surgery and adjuvant chemotherapy between 1994 and 2006. Only patients who had a complete response to chemotherapy verified by normal CT scan, CA-125 and physical examination were included. Nadir CA-125 level was defined as the first CA-125 measurement after completing chemotherapy. Available CA-125 values from diagnosis to recurrence or to last follow up were collected and evaluated for meeting any of the criteria above. Results: 91 patients with a median age of 59 (42 - 88) met the inclusion criteria. 82 patients had stage IIIC (90%) and 9 patients (10%) had stage IV. 86 patients (94.5%) had papillary serous histology and 88 patients had grade 3 (96.7%) disease. Median follow up was 43.7 months (12.6 - 156). Table 1 shows the number of patients who met any of the above CA-125 criteria in total and divided by the presence or absence of recurrence. There was no statistically significant difference in meeting any of the CA-125 criteria between the recurrence and no recurrence groups. Meeting at least one of the CA-125 criteria had 50% sensitivity, 65% specificity, and 86% positive predictive value for recurrence. The median time to recurrence in patients who met at least one CA-125 criteria was 3.8 months (0.2 - 12.4) and the median follow up time after meeting one of the CA 125 criteria in patients who did not recur was 88.5 months (10.4 - 188) Conclusions: Rising CA-125 levels within the normal range that meet any of the above criteria are highly predictive (86%) of recurrence within 12 months and closer observation is warranted. [Table: see text] No significant financial relationships to disclose.

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Concordance between CA-125 and RECIST progression (PD) in patients with germline BRCA-mutated platinum-sensitive, relapsed ovarian cancer treated with a PARP inhibitor (PARPi) as maintenance therapy after response to chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6014 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6014-6014 ◽

Cited By ~ 1

Author(s):

Angelina Tjokrowidjaja ◽

Chee Khoon Lee ◽

Michael Friedlander ◽

Val Gebski ◽

Laurence Gladieff ◽

...

Keyword(s):

Ovarian Cancer ◽

Positive Predictive Value ◽

Maintenance Therapy ◽

Predictive Value ◽

Parp Inhibitor ◽

Ca 125 ◽

Normal Range ◽

Primary Analysis ◽

Platinum Sensitive ◽

Response To Chemotherapy

6014 Background: There are no data to support CA-125 as a surrogate biomarker for ovarian cancer PD in patients on maintenance therapy with a PARPi. We aimed to assess the concordance of PD by CA-125 with RECIST PD in patients treated with maintenance PARPi. Methods: We extracted data on PD as defined by GCIG CA-125 and investigator-assessed RECIST from the SOLO2/ENGOT-Ov21 (NCT01874353) trial. Patients were categorized into: (i) CA-125 and RECIST non-PD concordant; (ii) CA-125 and RECIST PD concordant; and (iii) CA-125 and RECIST discordant. We excluded those with PD other than by RECIST, PD on date of randomization, and no repeat CA-125 beyond baseline. To assess the concordance of CA-125 PD with RECIST PD and CA-125 non-PD with RECIST non-PD, we computed the positive predictive value (PPV), i.e. the probability that patients with CA-125 PD also had RECIST PD, and negative predictive value (NPV), i.e. probability that patients with no CA-125 PD also did not have RECIST PD, respectively. Results: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included in the primary analysis. 80 (29%) had CA-125 PD and 77 had concordant RECIST PD, resulting in a PPV of 96% (95% CI 90%-99%). Of 195 patients without CA-125 PD, 101 also did not have RECIST PD, resulting in a NPV of 52% (95% CI 45%-59%; Table). Among those with RECIST PD (n = 171), a greater proportion of patients with RECIST-only PD had a normal baseline CA-125 than those with both CA-125 and RECIST PD (94% vs 69%; p< 0.001). Of 94 patients without CA-125 PD but had RECIST PD, 65 (69%) had CA-125 that remained within normal range, while 27 (29%) had rising and elevated CA-125 that did not meet the criteria for GCIG CA125-PD. Discordance between RECIST PD and CA-125 non-PD was similar in early (≤12 weeks) and late ( > 12 weeks) PD (56% vs 55%, respectively; p= 0.96). Conclusions: Almost half the patients with RECIST PD did not have CA-125 PD and most had CA-125 still within the normal range. Regular imaging should be considered as part of surveillance in patients on maintenance olaparib rather than relying on CA-125 alone. [Table: see text]

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Dynamic analysis of serum Ca-125 levels during neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer: a retrospective study

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20205412 ◽

2020 ◽

Vol 10 (1) ◽

pp. 88

Author(s):

Adarsh Dharmarajan ◽

A. Remya ◽

Aswathi Krishnan

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Proportional Hazards ◽

Disease Free Survival ◽

Ca 125 ◽

Free Survival ◽

Proportional Hazards Regression ◽

Response To Chemotherapy ◽

Neo Adjuvant Chemotherapy ◽

Disease Free

Background: Assessment of CA-125 kinetics was commonly used as a tool for tumor response to chemotherapy in ovarian cancer patients. The study aimed to determine any logarithmic/linear relationship between pre-chemotherapy and pre-operative CA-125 levels in ovarian cancer.Methods: Total 52 patients who underwent neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery were included. CA-125 levels before starting chemotherapy, during chemotherapy and the preoperative value, with the date of measurement recorded. Cox’s proportional hazards regression was used to evaluate univariate and independent multivariable association with the effect of clinical, pathological and CA-125 kinetic parameters on outcome endpoints. Results: The study couldn’t establish any relationship in logarithmic fall of CA-125 values among ovarian cancers as a result of neo-adjuvant chemotherapy. The disease-free survival among the patients was 12.2 months.Conclusions: There is an inverse relationship between serum CA-125 levels and survival in ovarian cancer. NACT resulted in adequate fall of CA-125 levels in most of the patients, but the rate of fall was not predictive of prognosis.

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Serum HE4 Profile During Primary Chemotherapy of Epithelial Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182225509 ◽

2011 ◽

Vol 21 (9) ◽

pp. 1573-1578 ◽

Cited By ~ 18

Author(s):

Johanna Hynninen ◽

Annika Auranen ◽

Kirsti Dean ◽

Maija Lavonius ◽

Olli Carpen ◽

...

Keyword(s):

Computed Tomography ◽

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Serum Biomarker ◽

Primary Chemotherapy ◽

Ca 125 ◽

Chemotherapy Response ◽

Primary Therapy ◽

Response To Chemotherapy

ObjectiveHuman epididymis protein 4 (HE4) is a promising novel serum biomarker for the detection of early-stage epithelial ovarian cancer (EOC) and for the differential diagnosis between benign and malignant ovarian tumors. The objective of the present study was to determine the value of HE4 for monitoring the response to primary therapy in patients with advanced disease.MethodsSerum HE4 and cancer antigen (CA) 125 levels of 10 patients with advanced EOC and one patient with adenocarcinoma of unknown origin were measured preoperatively and during first-line chemotherapy. Seven patients were treated with primary surgery and six cycles of chemotherapy. Response to treatment was evaluated 4 weeks after the completion of chemotherapy using computed tomography. Four patients received neoadjuvant chemotherapy (NACT) before surgery. To evaluate the early response to chemotherapy, changes in serum biomarker levels were compared with metabolic changes of tumors during NACT as detected by positron emission tomography/computed tomography.ResultsThe profile of HE4 during primary chemotherapy was in line with radiologic and clinical responses. In the neoadjuvant chemotherapy group, HE4 correlated better with the radiologic response than CA 125.ConclusionAssessment of serum HE4 may improve the reliability of response evaluation during chemotherapy for serous epithelial ovarian cancer.

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Initial assessment of tumor-associated antigen CA-125 in patients with ovarian, cervical, and testicular tumors.

Clinical Chemistry ◽

10.1093/clinchem/33.7.1124 ◽

1987 ◽

Vol 33 (7) ◽

pp. 1124-1125 ◽

Cited By ~ 3

Author(s):

P K Buamah ◽

C Cornell ◽

A W Skillen ◽

B M Cantwell ◽

A L Harris

Keyword(s):

Ovarian Cancer ◽

Initial Assessment ◽

Ca 125 ◽

Ovarian Teratoma ◽

Testicular Tumors ◽

Nonseminomatous Germ Cell Tumor ◽

Tumor Associated Antigen ◽

Response To Chemotherapy ◽

Glycoprotein Antigen ◽

Monitoring Response

Abstract Serum CA-125, a glycoprotein antigen, has been measured in serum of patients with ovarian cancer, cervical cancer, or nonseminomatous germ-cell tumor of testis. Increased concentrations were found in 21 of 27 patients with epithelial ovarian cancer and two of three patients with ovarian teratoma. Changes in CA-125 concentrations in serum during chemotherapy mirrored the progress of the disease as assessed by clinical and radiological evidence. Although CA-125 provides no real asset for diagnosis, it should have value as a marker for monitoring response to chemotherapy.

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Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

The International Journal of Biological Markers ◽

10.1177/1724600820955195 ◽

2020 ◽

Vol 35 (4) ◽

pp. 20-27 ◽

Cited By ~ 1

Author(s):

Enrico Potenza ◽

Giulia Parpinel ◽

Maria E. Laudani ◽

Chiara Macchi ◽

Luca Fuso ◽

...

Keyword(s):

Ovarian Cancer ◽

Predictive Value ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

Serum Levels ◽

Ca 125 ◽

Free Survival ◽

The Third ◽

Response To Chemotherapy

Introduction: At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. Methods: We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016–2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Results: Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). Conclusions: We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

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Bispecific T-Cell Engaging Antibodies Against MUC16 Demonstrate Efficacy Against Ovarian Cancer in Monotherapy and in Combination With PD-1 and VEGF Inhibition

Frontiers in Immunology ◽

10.3389/fimmu.2021.663379 ◽

2021 ◽

Vol 12 ◽

Author(s):

Oladapo O. Yeku ◽

Thapi Dharma Rao ◽

Ian Laster ◽

Artem Kononenko ◽

Terence J. Purdon ◽

...

Keyword(s):

Ovarian Cancer ◽

Xenograft Model ◽

Tumor Burden ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Single Chain ◽

Anti Vegf ◽

Relapsed Disease

Immunotherapy for ovarian cancer is an area of intense investigation since the majority of women with relapsed disease develop resistance to conventional cytotoxic therapy. The paucity of safe and validated target antigens has limited the development of clinically relevant antibody-based immunotherapeutics for this disease. Although MUC16 expression is almost universal in High Grade Serous Ovarian Cancers, engagement of the shed circulating MUC16 antigen (CA-125) presents a theoretical risk of systemic activation and toxicity. We designed and evaluated a series of bispecific tandem single-chain variable fragments specific to the retained portion of human MUC16 ectodomain (MUC16ecto) and human CD3. These MUC16ecto- BiTEDs retain binding in the presence of soluble MUC16 (CA-125) and show cytotoxicity against a panel of ovarian cancer cells in vitro. MUC16ecto- BiTEDs delay tumor progression in vivo and significantly prolong survival in a xenograft model of ovarian peritoneal carcinomatosis. This effect was significantly enhanced by antiangiogenic (anti-VEGF) therapy and immune checkpoint inhibition (anti-PD1). However, the combination of BiTEDs with anti-VEGF was superior to combination with anti-PD1, based on findings of decreased peritoneal tumor burden and ascites with the former. This study shows the feasibility and efficacy of MUC16ecto- specific BiTEDs and provides a basis for the combination with anti-VEGF therapy for ovarian cancer.

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RATIO OF SERUM CA125 TO RADIOLOGICAL PERITONEAL CARCINOMATOUS INDEX AS A NOVEL MARKER OF RESPONSE TO NEO ADJUVANT CHEMOTHERAPY AND PREDICTIVE MODEL OF SURGICAL OUTCOME IN ADVANCED EPITHELIAL OVARIAN CANCER- A SINGLE INSTITUITIONAL STUDY.

10.36106/ijar/5408387 ◽

2020 ◽

pp. 1-3

Author(s):

Prem Kumar Devdoss ◽

Prasanna Srinivasa Rao H ◽

N. Roobalakshmi

Keyword(s):

Ovarian Cancer ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Ca 125 ◽

Newly Diagnosed ◽

Response To Chemotherapy ◽

Serum Ca125 ◽

Advanced Epithelial Ovarian Cancer ◽

Neo Adjuvant Chemotherapy

Objective: The objective of this retrospective study is to develop a novel marker- ratio of serum CA 125 to peritoneal carcinomatous index(PCI) - to predict the response in women receiving neoadjuvant chemotherapy for newly diagnosed advanced epithelial ovarian cancer at our centre. Methods: Medical records of women who were newly diagnosed with inoperable advanced ovarian cancer stages III and IV at our centre were selected. Only people with completely documented records in the years 2017 & 2018 were selected. Only patietns with serous histology were chosen. Pre chemotherapy serum CA125 value was noted. Radiological PCI was calculated by reviewing the CECT films & reports of the patients. Patients were compared with the ratio of CA125 to radiological PCI and clinical & pathological response to neo adjuvant chemotherapy. All patients received standard doses of three weekly Paclitaxel and Carboplatin based chemotherapy. Based on the ratio of CA125 to PCI patients were divided into 2 groups – ratio more than 100 and less than 100. Results: A total of 34 were patients were found to meet the eligible criteria. Response assessment was done after 3 to 4 cycles of neoadjuvant chemotherapy. The overall response rate to neoadjuvant chemotherapy in patients in group 1 ( CA125/PCI ratio > 100) was significantly higher as compared to patients in group 2 (CA125/PCI ratio <100). Conclusion: In summary, CA 125 to PCI ratio is novel method to predict response to chemotherapy in advanced epithelial ovarian cancers. This value is a helpful measurement that allows the clinicians to measure the degree of chemosensitivity prior to cytoreductive surgery. This measures the inherent tumor biology and to aids in surgical decision making regarding the role and extent of cytoreduction as well as alternate systemic/local therapies.

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