Ovarian Cancer Surveillance Research Articles

Serum folate receptor α (sFR) in ovarian cancer diagnosis and surveillance.

Novelty and Impact Statement: Our findings suggest that soluble folate receptor (sFR) could be used in both the initial diagnosis and surveillance of patients with ovarian cancer. Our cohort constitutes one of the largest comparison groups for sFR analyzed so far. We have defined the background level of sFR using healthy volunteers. This is also the first study to prospectively follow patients in the surveillance setting to concurrently identify differential changes in tumor markers CA‐125 and sFR.

Incidental Thoracic Findings on Routine Computed Tomography in Epithelial Ovarian Cancer.

Multidetector computed tomography (MDCT) is routinely used in the surveillance of epithelial ovarian cancer. The aim of this study was to determine the incidence of thoracic findings on routine MDCT surveillance imaging in patients with ovarian carcinoma. Retrospective evaluation of 100 MDCT studies of patients with a diagnosis of epithelial ovarian cancer was performed at a university teaching hospital. The cross-sectional studies were reviewed by a consultant radiologist with subspeciality training in cross-sectional imaging. Intrathoracic findings were identified in 35% of patients. Pleural effusions were identified in 40%, pulmonary nodules in 37%, mediastinal adenopathy in 17%, and thyroid nodules in 6% of patients. Thirty-five (35%) patients were found to have thoracic findings on computed tomography. Pleural effusions developed in 14 (40%) of these patients. Small lung nodules (<1 cm) were present in 13 (37%) patients. Mediastinal lymphadenopathy was seen in 6 (17%) patients. Two patients (6%) had thyroid nodules of unknown significance. Pleural effusions and small lung nodules were present at a similar level to that of the general population. This retrospective study supports the imaging recommendations of the European Society of Urogenital Radiology that MDCT protocols for the initial staging and evaluation of recurrent disease in epithelial ovarian carcinoma require only inclusion of the lung bases to the inguinal region reducing exposure to ionizing radiation, alleviating patient anxiety, and offering a cost-benefit to hospitals.

High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels

PurposeThe aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. MethodsThis institutional review board–approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 ± 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross-validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. ResultsRate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). ConclusionA higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer.

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy.

Due to the critical role of T cells in the immune surveillance of ovarian cancer, adoptive T-cell therapies are receiving increased attention as an immunotherapeutic approach for ovarian cancer. Chimeric antigen receptors (CARs), constructed by incorporating the single-chain Fv fragment to a T-cell signaling domain such as CD3 ζ or Fc receptor γ chain, endow T cell with nonmajor histocompatibility complex-restricted specificity. Dual specificity, trans-signaling CARs and affinity-tuned single-chain Fv fragment have broadened the applicability of CAR-engineered T-cell therapy and may be considered preferential to T cell receptor T-cell therapy in clinical care. As new insights into the CAR-engineered T cells have emerged over the last decade, we review the development of CAR T-cell therapy and discuss the progress and safety concerns regarding its translation from basic research into clinical care of ovarian cancer.

Symptoms Relevant to Surveillance for Ovarian Cancer.

To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001). Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2%) than women reporting no symptoms (11,882/18,355 = 64.7%), p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported.

Clinical management of patients at inherited risk for gynecologic cancer.

As more women with an inherited increased risk of gynecologic cancer are identified, the clinician will be challenged to counsel these women on risk-reducing strategies. Although there are some recent studies that show potential for ovarian cancer surveillance strategies, there remains no definitive evidence that surveillance leads to a stage shift or a reduction in mortality. Recent studies support the following conclusions: first, oral contraceptive use reduces ovarian cancer risk without significantly increasing breast cancer risk, second, salpingo-oophorectomy leads to a reduction in ovarian cancer, breast cancer, and overall mortality for women who are carriers of BRCA1 and BRCA2 mutations, and third, the 'ovarian cancers' associated with BRCA mutations actually include fallopian tube and peritoneal cancer and may have a precursor lesion in the fallopian tube; this observation has prompted the provocative suggestion of removing the fallopian tube to reduce ovarian cancer risk. Because of the interplay between the hormonal impact of ovarian function on breast cancer risk, the risk reduction associated with oophorectomy, and the impact of early menopause on other health outcomes, an integrated multidisciplinary approach is required to aid in the increasingly complex decisions faced by women with high inherited risk of developing gynecologic cancers.

術後サーベイランスで乳房超音波が有用であった遺伝性乳癌の1例

術後サーベイランスで乳房超音波が有用であった遺伝性乳癌の1例

Abstract 4712: Personalized ovarian cancer surveillance and detection of a therapeutic drug target in circulating tumor DNA

Abstract Retrospective studies have demonstrated that nearly 50% of ovarian cancer patients with normal CA125 levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here we demonstrate that for one patient, with the first reported FGFR2 fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125 and it can also inform on a candidate therapeutic. Over a four year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences and multiple chemotherapeutic regimens, blood samples were longitudinally-collected and stored. Whereas post-surgical CA125 levels were elevated only three times over 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by qtRT-PCR in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and other with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhbitor treatment. Using the same overall approach, ctDNA is demonstrated in other patients and the results compared to CA125. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease. To our knowledge, this use of a personalized biomarker represents the first example in ovarian cancer demonstrating the presence of continuous occult disease in the face of negative clinical, radiologic and biochemical examination. Moreover, the recent identification of FGFR fusions in other solid cancers suggests a broader application of this strategy beyond ovarian cancer. Citation Format: John A. Martignetti, Olga Camacho-Vanegas, Nolan Priedigkeit, Catalina Camacho-Vanegas, Elena Pereira, Li Lin, Bojan Losic, hardik Shah, Jun Liao, Jian Ma, Pratik Lahiri, Mark Chee, Eric Schadt, Peter Dottino. Personalized ovarian cancer surveillance and detection of a therapeutic drug target in circulating tumor DNA. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4712. doi:10.1158/1538-7445.AM2014-4712

Is there an impact of 18F-FDG PET/CT on the surveillance and clinical management of recurrent ovarian cancer? Research based on a large sample in a single PET/CT center

The aim of the study was to evaluate the use of F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) in the follow-up and clinical management of ovarian cancer patients after therapy. A total of 152 ovarian cancer patients who had undergone therapy were evaluated. Clinical information, CA-125 levels, and traditional imaging findings were analyzed. According to the indication for PET/CT the patients were divided into five groups for assessing the role of (18)F-FDG PET/CT in the clinical management of ovarian cancer patients after therapy. A comparison was made between the PET/CT findings and the results of clinical follow-up. Of the 152 patients, 137 had follow-up results and 15 were lost to follow-up. A total of 105 patients were found to have recurrent tumor and 32 were found to be disease-free after long-term follow-up. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 98.3, 91.2, 96.8, 97.5, and 93.9%, respectively. PET/CT was especially useful in patients when indications were to diagnose suspected recurrence, assess disease progression, and evaluate therapeutic response. PET/CT has been proven to be extremely valuable in the evaluation of patients with recurrent ovarian cancer and is particularly helpful in guiding treatment planning.

BRCA Mutation Carriers Do Not Have Compromised Ovarian Reserve

Controversy exists about the impact of BRCA1/2 mutations on female fertility. Previous studies are small or based on indirect parameters (eg, self-reported infertility), which depend on additional factors unrelated to true fertility potential. Most of the previous studies did not use strict fertility markers. The aim of this study is to evaluate the relation between carrying a BRCA1/2 mutation and fertility using the level of anti-müllerian hormone (AMH), which has been previously shown to be an accurate marker of ovarian reserve and fertility potential. Forty-one healthy BRCA1/2 mutation carriers, aged 26 to 40 years, attending a multidisciplinary breast and ovarian cancer surveillance clinic, were tested for AMH levels using a 2-site ELISA. Levels were compared with those of our general population and with well-established normograms of the general population. The mean age of carriers was 33.2 years (26-39 years; SD, 3.99 years). The mean parity of carriers was 1.97 (0-7; SD, 1.49). All women carried at least 1 Ashkenazi Jewish founder mutation. The AMH levels for most carriers were in the reference range, 2.71 ± 0.59 ng/mL (approximately 50th percentile of normograms). These levels were similar to those in the control group, in which the AMH levels were 2.02 ± 0.12 ng/mL (P = 0.27). The AMH levels of healthy BRCA1/2 mutation carriers are similar to those of noncarrier women matched for age; therefore, their ovarian reserve is comparable. This is the only study, to the best of our knowledge, that directly examines ovarian reserve in a relatively large group of carriers with an accurate marker. The results of this study may possibly give reassurance to female carriers concerning fertility potential.

The special role of ultrasound for screening, staging and surveillance of malignant ovarian tumors: distinction from other methods of diagnostic imaging

Ovarian cancer is the most aggressive gynecologic malignancy, with a 5-year survival rate ranging around 40%. A crucial factor influencing the prognosis is early detection of a suspicious mass and referral to a gynecologic oncology center for further diagnosis, staging and debulking surgery. Here, we present the different imaging methods ultrasound (US), magnetic resonance imaging, computer tomography (CT) and 18F-fluoro-deoxyglucose positron emission tomography (PET)/CT that are used for the characterization, diagnosis, staging and surveillance of ovarian cancer. In this review, we focus on US and discuss in detail the advantages and the limitations, as well as the appropriate indications for each of the individual imaging techniques.

Additional CT scan too costly in ovarian cancer surveillance?

Additional CT scan too costly in ovarian cancer surveillance?

Patient surveillance after curative-intent treatment for ovarian cancer: What motivates clinicians?

e15528 Background: In the US, ovarian cancer is diagnosed in &gt; 20,000 women and causes &gt;13,000 deaths each year. After curative-intent initial treatment, surveillance is common. Marked variation in surveillance intensity has been documented, suggesting overuse and/or underuse of resources. We sought to determine what factors motivate gynecologic oncologists as they design their surveillance strategies. Methods: A survey about ovarian cancer surveillance after initial treatment was mailed to all 943 members of the Society of Gynecologic Oncologists. The survey included 14 questions about putative motivating factors. Responses were submitted on a 10-level Likert scale. Motivating factors were ranked by the percent of responses for each of the ten levels. Results: 323 of the 943 (34%) responded; 283 responses were evaluable. “Current literature documents significant survival benefits” was the weakest motivating factor. Conclusions: The table below is consistent with the lack of evidence that any particular surveillance strategy confers any survival benefit. This is the first empirical evidence concerning factors that may motivate gynecologic oncologists in designing their surveillance strategies. Understanding motivating factors may be useful in devising methods to diminish the marked variation in strategies. [Table: see text]

Beyond evidence: reappraising use of CA‐125 as post‐therapy surveillance for ovarian cancer

Beyond evidence: reappraising use of CA‐125 as post‐therapy surveillance for ovarian cancer

Utility of “reflex” CT scans during surveillance of serous ovarian cancer

Objective: CA125 surveillance for recurrent ovarian cancer has come under increasing scrutiny. However, it remains widely used by many clinicians, and its first elevation often leads to a “reflex” CT scan. The objective of this study was to evaluate the yield of the CT scan obtained at time of first CA125 elevation.

Decreased levels of serum glutathione peroxidase 3 are associated with papillary serous ovarian cancer and disease progression

BackgroundGlutathione peroxidase 3 (GPX3) is a selenocysteine-containing antioxidant enzyme that reacts with hydrogen peroxide and soluble fatty acid hydroperoxides, thereby helping to maintain redox balance within cells. Serum levels of GPX3 have been found to be reduced in various cancers including prostrate, thyroid, colorectal, breast and gastric cancers. Intriguingly, GPX3 has been reported to be upregulated in clear cell ovarian cancer tissues and thus may have implications in chemotherapeutic resistance. Since clear cell and serous subtypes of ovarian cancer represent two distinct disease entities, the aim of this study was to determine GPX3 levels in serous ovarian cancer patients and establish its potential as a biomarker for detection and/or surveillance of papillary serous ovarian cancer, the most frequent form of ovarian tumors in women.Patients and MethodsSerum was obtained from 66 patients (median age: 62 years, range: 22-89) prior to surgery and 65 controls with a comparable age-range (median age: 53 years, range: 25-83). ELISA was used to determine the levels of serum GPX3. The Mann Whitney U test was performed to determine statistical significance between the levels of serum GPX3 in patients and controls.ResultsSerum levels of GPX3 were found to be significantly lower in patients than controls (p = 1 × 10-2). Furthermore, this was found to be dependent on the stage of disease. While levels in early stage (I/II) patients showed no significant difference when compared to controls, there was a significant reduction in late stage (III/IV, p = 9 × 10-4) and recurrent (p = 1 × 10-2) patients. There was a statistically significant reduction in levels of GPX3 between early and late stage (p = 5 × 10-4) as well as early and recurrent (p = 1 × 10-2) patients. Comparison of women and controls stratified to include only women at or above 50 years of age shows that the same trends were maintained and the differences became more statistically significant.ConclusionsSerum GPX3 levels are decreased in women with papillary serous ovarian cancer in a stage-dependent manner and also decreased in women with disease recurrence. Whether this decrease represents a general feature in response to the disease or a link to the progression of the cancer is unknown. Understanding this relationship may have clinical and therapeutic consequences for women with papillary serous adenocarcinoma.

Abstract 3661: The impact of tumor-infiltrating natural killer cells on ovarian cancer progression

Abstract Cancers adopt diverse strategies to safeguard their survival by evading tumor surveillance. Natural killer (NK) cells and CD8 T-lymphocytes are capable of destroying tumor cells thus playing a critical role in tumor immunity. In previous studies, we showed that NK cell derived TRAIL is essential for the cytotoxic activity of the DR5 agonistic antibody AD5-10, since depletion of NK cells abolished the antitumor activity of AD5-10 in a xenograft ovarian cancer (OC) mouse model. In the present study, we investigated whether NK cells are associated with clinical outcome as well as with the immune infiltrate showing anti-tumor immunity in OC. We analyzed NK cell infiltration in human primary ovarian tumor tissues using immunohistochemical analysis of a representative population of OC patients on a tissue microarray. NK tumor-infiltrating cells were detected within tumor tissues, whereas CD3 tumor-infiltrating T-lymphocytes were almost undetectable. NK cells in addition inversely correlated with FIGO stage (r=−0.51, p&amp;lt;0.001) and tumor grade (r=−0.3, p=0.03). These data indicate that the presence of intratumoral NK cells correlates with improved clinical outcome in OC. When we analyzed the cytotoxic capacity of human NK cells against OC cells in vitro, we found that human NK cells were capable to induce apoptosis in a concentration-and time-dependent manner in several OC cell lines. Interestingly, the addition of the DR5 agonistic antibody AD5-10 sensitized TRAIL resistant OC cell lines to NK cells mediated cytolysis. To study tumor surveillance of OC in vivo, we are currently setting up mouse models. Transformed murine ovarian surface epithelial (MOSE) cell lines derived from C57BL/6 mice have been implanted intraperitoneally into syngenic wild type, RAG2 -/-, RAG2 -/- γ -/-, NK depleted, CD8 depleted C57BL/6 recipient mice. The outcome of these studies will be presented. In summary, our findings point at a critical role for NK cell mediated tumor surveillance for OC development. Importantly, NK cell infiltration correlates with prognosis in human ovarian carcinoma. Thus, our study may open novel therapeutic opportunities by interfering with host immunity in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3661. doi:10.1158/1538-7445.AM2011-3661

A systematic review of gynecological cancer surveillance in women belonging to hereditary nonpolyposis colorectal cancer (Lynch syndrome) families

We performed a systematic review of studies that evaluate the role of gynecological cancer surveillance in women who carry a hereditary nonpolyposis colorectal cancer (HNPCC) mutation or belong to a family that fulfills the criteria for HNPCC. The PubMed database and a clinical trials database were used to identify relevant studies. We included studies that reported results of gynecological cancer surveillance in women who carry a HNPCC mutation, belong to a family in which a HNPCC mutation was detected or belong to a family fulfilling the Amsterdam II criteria. Number and stage of cancers, interval cancers and cancer precursor states detected at screening. Five studies fulfilled our review criteria. Surveillance modalities for endometrial cancer included transvaginal ultrasound combined with endometrial sampling when indicated, or transvaginal ultrasound with a routine endometrial biopsy, and, in certain studies, the tumor marker CA-125. The highest yield of pathological findings in surveillance visits, from 5 to 6.5%, occurred in studies that included routine endometrial biopsies. Without a routine sampling, 7/14 cancers and 11/18 hyperplasias would have been missed. One case of advanced ovarian cancer was detected at surveillance. Currently available published studies on gynecological cancer surveillance in women with HNPCC do not adequately allow for evidence-based clinical decisions. Detection of endometrial cancer or hyperplasia in nonsymptomatic women belonging to an HNPCC family is improved by adding routine endometrial sampling along with transvaginal ultrasound for surveillance visits. No benefit was shown for ovarian cancer surveillance.

腎コレステリン肉芽腫の1例

A 58-year-old woman was referred to our outpatient clinic for further examination of a mass detected in the right kidney on follow-up ultrasonography performed for active surveillance of right ovarian cancer. Ultrasonography and computed tomography showed a cyst (diameter, 30 mm) with an irregular wall in the middle of the right kidney. Right nephrectomy was performed since malignancy was suspected. Histological findings of the mass indicated cholesterol granuloma. Although cholesterol granulomas in the middle ear have been frequently reported, those in other organs have been reported in few studies. In this patient, the cholesterol granuloma could be barely distinguished from the cancer by using imaging techniques.

Cancergazing? CA125 and post-treatment surveillance in advanced ovarian cancer

Post-treatment surveillance of advanced ovarian cancer involves regular testing of asymptomatic patients using the CA125 test. This practice is based on a rationale that is not supported by evidence from clinical trials. This paper aims to stimulate critical reflection concerning the effect of investigative tests on clinical decisions and interactions, and the experience of illness, particularly in the context of advanced malignant disease. Drawing on the idea of the "medical gaze", and building on previous health communication research, we present an analysis of in-depth interviews and psychometric tests collected in a prospective study of 20 Australian women with advanced ovarian cancer conducted between 2006 and 2009. We describe the demands placed on patients by the use of the CA125 test, some hazards it creates for decision-making, and some of the test's subjective benefits. It is widely believed that the CA125 test generates anxiety among patients, and the proposed solution is to educate women more about the test. We found no evidence that anxiety was a problem requiring a response over and above existing services. We conclude that the current debate is simplistic and limited. Focussing on patient anxiety does not account for other important effects of post-treatment surveillance, and educating patients about the test is unlikely to mitigate anxiety because testing is part of a wider process by which patients become aware of a disease that--once it has relapsed--will certainly kill them in the near future.