Elevated CYFRA Research Articles

Predictive Value of Serum CYFRA21-1 and CK19-2G2 for Tumor Aggressiveness and Overall Survival in Hepatitis C-Related Hepatocellular Carcinoma Among Egyptians: A Prospective Study.

Cytokeratin 19 fragment 21-1 (CYFRA 21-1) and cytokeratin 19 fragment 2G2 (CK 19-2G2) are two soluble fragments of cytokeratin 19 (CK 19) that can be detected in serum. CK 19-positive hepatocellular carcinoma (HCC) is characterized by anaggressive behavior and a poor outcome. This study aimed to assess the prognostic value of serum CYFRA 21-1 and CK 19-2G2 in predicting tumor aggressiveness and overall survival (OS) in patients with hepatic C virus (HCV)-related HCC. The current study included 138 patients with HCV-related HCC recruited from the Hepatobiliary and Interventional Radiology Units at Alexandria's main university hospitals and 40 healthy individuals as controls. Patients were assessed for clinical, radiological tumor characteristics, and aggressiveness index. Baseline serum CYFRA 21-1 and CK 19-2G2 levels were measured by enzyme-linked immunosorbent assay. Elevated CYFRA 21-1 levels were associated with tumors size ≥ 5 cm (p < 0.001), malignant portal vein thrombosis (mPVT) (p < 0.001), distant metastasis (p = 0.030), ill-defined/infiltrative pattern (p = 0.010), and aggressiveness index > 4 (p = 0.045). Elevated CK19-2G2 levels were not associated with any clinical or radiological characteristics. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 in combination with alpha-feto protein (AFP) ≥ 400 ng/ml have a better predictability for mPVT and ill-defined/infiltrative patterns (sensitivity (10-25%) and specificity (96-100%)). Elevated levels of CYFRA 21-1, CK 19-2G2, or AFP ≥ 400 ng/ml were associated with decreased 1-year OS. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 levels when added to AFP ≥ 400 ng/ml are specific but less sensitive biomarkers for predicting tumor aggressiveness. These biomarkers can be used independently to predict reduced 1-year OS in Egyptian patients with HCV-related HCC.

Association of serum tumor markers with serous effusion in systemic lupus erythematosus

The objective of this study was to investigate the relationship between serum tumor markers and serous effusion in systemic lupus erythematosus (SLE) patients, thereby contributing preliminary data on the utility of these tumor markers in diagnosing serous effusion. In this retrospective analysis, clinical data of SLE patients were extracted from electronic medical records. This included the levels of serum tumor markers, including pro-gastrin-releasing peptide, neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), various carbohydrate antigens (CA 153, CA 125, CA 19-9), along with carcinoembryonic antigen, and alpha-fetoprotein. Positivity of tumor markers was established based on serum levels surpassing the upper threshold of the respective reference ranges. This study included 149 eligible patients with SLE, of whom 38 (25.50%) had serous effusion, and the prevalence of pleural, pericardial, and peritoneal effusions was 11.41%, 14.77%, and 6.71%, respectively. The analysis revealed that patients with serous effusion had higher scores on the SLE Disease Activity Index 2000 (SLEDAI 2000) than those without serous effusion. Notably, this disparity remained significant when the serositis score was excluded from the SLEDAI 2000 calculation. The positivity rate and serum levels of CA 125 were higher in patients with serous effusion and pleural effusion. Patients with pericardial effusion demonstrated an elevated CYFRA 21-1 positivity rate and serum CA 125 and CYFRA 21-1 levels compared to patients without pericardial effusion. CA 125 and NSE were higher both in terms of positivity rate and serum levels for patients with peritoneal effusion. Through receiver operating characteristic curve analysis, a moderate relationship was discerned between the conjoined levels of CYFRA 21-1 and CA 125 and the occurrence of pericardial effusion. Additionally, CA 125, NSE, and their combination revealed the moderate diagnostic ability of peritoneal effusion. In summary, this study observed elevated serum levels of various tumor markers in SLE patients exhibiting serous effusion, which is likely attributable to lupus-induced inflammation. These findings suggest that serum tumor markers can be valuable in diagnosing pericardial and peritoneal effusions.

Variability of serum CYFRA 21 − 1 and its susceptibility to clinical characteristics in individuals without cancer: a 4-year retrospective analysis

BackgroundCYFRA 21 − 1 is a useful marker for diagnosing and monitoring lung cancer. However, its stability remains unclear. Moreover, while its applicability to screening is now being investigated, CYFRA 21 − 1 levels in individuals without cancer, who are targets for cancer screening, have not yet been the focus of research. Therefore, the present study investigated variability in and the factors increasing serum CYFRA 21 − 1 levels.MethodsThis retrospective study recruited 951 individuals undergoing annual medical examinations for six years. We used data obtained in the first four years. Variability in serum CYFRA 21 − 1 levels over a period of four years were investigated. CYFRA 21 − 1 was categorized as normal (≤ 3.5 ng/ml) or elevated (> 3.5 ng/ml). The rate of an elevated level in one visit and the transition from an elevated to normal level between visits were visualized. A multiple logistic regression model was used to study the relationships between the frequency of elevated CYFRA 21 − 1 levels and clinical characteristics, such as age, sex, body mass index, weight changes, and the smoking status.ResultsApproximately 5% of subjects had elevated CYFRA 21 − 1 levels once in five tests over four years, while 15% had elevated CYFRA 21 − 1 levels once or more. Among subjects with elevated CYFRA 21 − 1 levels in one blood test, between 63 and 72% had normal levels in the next test. The median CYFRA 21 − 1 level in subjects with elevations in one blood test significantly decreased in the next test at all four time points. The frequency of elevated CYFRA 21 − 1 levels was associated with an older age [odds ratio (OR) = 6.99, 95% confidence interval (CI) = 3.01–16.2], current heavy smoking (OR = 3.46, 95% CI = 1.52–7.9), and weight loss (OR = 1.86, 95% CI = 1.07–3.24).ConclusionsVariability in and the factors increasing serum CYFRA 21 − 1 levels beyond the cut-off value need to be considered when interpretating CYFRA 21 − 1 test results. The future application of CYFRA 21 − 1 to lung cancer screening may require more than a single measurement.

Clinical Efficacy and Safety of First- or Second-Generation EGFR-TKIs after Osimertinib Resistance for EGFR Mutated Lung Cancer: A Prospective Exploratory Study.

Osimertinib monotherapy is a common treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC); however, standard treatment strategies for acquired resistance to this drug have not been established. In addition, the clinical significance of first-generation (1G) or second-generation (2G) EGFR-tyrosine kinase inhibitors (TKI) in patients with EGFR-mutant NSCLC and osimertinib resistance has not yet been fully evaluated. We aimed to conduct a prospective multicenter observational study to evaluate the efficacy and safety of 1G and 2G EGFR-TKIs after the development of osimertinib resistance. Patients with EGFR-mutant NSCLC who received 1G or 2G EGFR-TKIs after developing resistance to osimertinib monotherapy were prospectively assessed at eight institutions in Japan. The primary endpoint was progression-free survival (PFS). A total of 29 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. The objective response and disease control rates were 6.9% (2/29) and 58.6% (17/29), respectively. The median PFS was 1.9 months [95% confidence interval (CI): 1.3-5.3]. There was no significant difference in PFS between the 1G and 2G EGFR-TKI groups (3.7 versus 1.5 months, log-rank test p = 0.20). However, patients with normal cytokeratin 19 fragment (CYFRA 21-1) and pro-gastrin-releasing peptide (ProGRP) levels experienced longer PFS than those with elevated CYFRA 21-1 and/or ProGRP (5.5 versus 1.3 months, log-rank test p < 0.001). Administration of 1G or 2G EGFR-TKIs after the development of osimertinib resistance has limited efficacy in patients with EGFR-mutant NSCLC. Moreover, normal CYFRA 21-1 and ProGRP levels could be promising indicators for 1G and 2G EGFR-TKI administration after osimertinib resistance development. UMIN000044049.

Pretreatment Serum Levels of Soluble Cytokeratin Fragments (Cyfra 21-1, TPS, MonoTotal) in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay. In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels. Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors. The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation.

Development and validation of a model to predict tyrosine kinase inhibitor-sensitive EGFR mutations of non-small cell lung cancer based on multi-institutional data.

BackgroundNon‐small cell lung cancer (NSCLC) with different EGFR mutation types shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study developed a patho‐clinical profile‐based prediction model of TKI‐sensitive EGFR mutations.MethodsThe records of 1121 Chinese patients diagnosed with NSCLC from November 2008 to October 2014 (the development set) were reviewed. Multivariate logistic regression was conducted to identify any association between potential predictors and the classic sensitive EGFR mutations (exon 19 deletion and exon 21 L858R point mutation). A prediction index was created by assigning weighted scores to each factor proportional to a regression coefficient. Validation was made in an independent cohort consisting of 864 patients who were consecutively enrolled between November 2014 and January 2017 (the validation set).ResultsSeven independent predictors were identified: gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs. yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no), and elevated Cyfra 21‐1 (no vs. yes). Each was assigned a number of points. In the validation set, the area under curve of the prediction index appeared as 0.698 (95% confidence interval 0.663–0.733). The sensitivity, specificity, positive and negative predictive values, and concordance were 95.0%, 32.3%, 61.4%, 85.1%, and 65.6%, respectively.ConclusionWe developed a patho‐clinical profile‐based model for predicting TKI‐sensitive EGFR mutations. Our model may represent a noninvasive, economical choice for clinicians to inform TKI therapy.

PD23-06 ROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH T1G3 OR MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Detection and Screening I1 Apr 2015PD23-06 ROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH T1G3 OR MUSCLE INVASIVE BLADDER CANCER Akihiro Yano, Hironori Sugiyama, Eiken Cho, Hideki Takeshita, Yohei Okada, Hideki Nagamatsu, Makoto Morozumi, Satoru Kawakami, and Takumi Yamada Akihiro YanoAkihiro Yano More articles by this author , Hironori SugiyamaHironori Sugiyama More articles by this author , Eiken ChoEiken Cho More articles by this author , Hideki TakeshitaHideki Takeshita More articles by this author , Yohei OkadaYohei Okada More articles by this author , Hideki NagamatsuHideki Nagamatsu More articles by this author , Makoto MorozumiMakoto Morozumi More articles by this author , Satoru KawakamiSatoru Kawakami More articles by this author , and Takumi YamadaTakumi Yamada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1422AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES No serum prognosticator has been established in patients with potentially lethal bladder cancer. The aim of this study is to evaluate the prognostic value of serum CYFRA 21-1 (CYFRA) in these patients. METHODS Serum levels of CYFRA and C-reactive protein (CRP) were measured in 70 patients with T1G3 or muscle invasive bladder cancer between Jan 2010 and Jan 2014. Cut-off values of CYFRA and CRP were determined by receiver operating characteristic analyses. Prognostic values of age, stage, CYFRA and CRP were evaluated using multivariate analysis with a Cox proportional hazards model. RESULTS The median (range) values of CYFRA, and CRP were 3.0 (1.1-87.8) ng/mL and 0.2 (0-19.4) mg/dL, respectively. The median (range) age and follow-up period was 72 (38-92) years and 14.2 (1.1-36.9) months. Prognostic values of age (< 72 vs. ≥ 72), stage (non-metastatic vs. metastatic), CYFRA (cut-off 3.6 ng/mL) and CRP (cut-off 1.8 mg/dL) were evaluated dichotomously. Multivariate analyses revealed that both of p-values for stage and CRP are 0.09, and only CYFRA (P < 0.001) is a significant and an independent prognosticator. In 45 patients with non-metastatic disease, those with elevated CYFRA had 20.3-fold higher risk of cancer specific mortality than those with non-elevated CYFRA. In 25 patients with metastatic disease, those with elevated CYFRA had 4.6-fold higher risk of cancer specific mortality than those with non-elevated CYFRA. CONCLUSIONS The current results indicate that serum CYFRA level can be a prognosticator for patients with potentially lethal bladder cancer. Further prospective analyses will be needed to confirm our results. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e482-e483 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Yano More articles by this author Hironori Sugiyama More articles by this author Eiken Cho More articles by this author Hideki Takeshita More articles by this author Yohei Okada More articles by this author Hideki Nagamatsu More articles by this author Makoto Morozumi More articles by this author Satoru Kawakami More articles by this author Takumi Yamada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP2-04 PROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH G3 OR MUSCLE INVASIVE UPPER URINARY TRACT CANCER

You have accessJournal of UrologyBladder Cancer: Upper Tract TCC I1 Apr 2015MP2-04 PROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH G3 OR MUSCLE INVASIVE UPPER URINARY TRACT CANCER Akihiro Yano, Hironori Sugiyama, Eiken Cho, Hideki Takeshita, Yohei Okada, Hideki Nagamatsu, Makoto Morozumi, Satoru Kawakami, and Takumi Yamada Akihiro YanoAkihiro Yano More articles by this author , Hironori SugiyamaHironori Sugiyama More articles by this author , Eiken ChoEiken Cho More articles by this author , Hideki TakeshitaHideki Takeshita More articles by this author , Yohei OkadaYohei Okada More articles by this author , Hideki NagamatsuHideki Nagamatsu More articles by this author , Makoto MorozumiMakoto Morozumi More articles by this author , Satoru KawakamiSatoru Kawakami More articles by this author , and Takumi YamadaTakumi Yamada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.127AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES No serum prognosticator has been established in patients with potentially lethal upper urinary tract cancer (UUTC). The aim of this study is to evaluate the prognostic value of serum CYFRA 21-1 (CYFRA) in these patients. METHODS Serum levels of CYFRA and C-reactive protein (CRP) were measured in 30 patients with G3 or muscle invasive UUTC between Jan 2012 and Aug 2014. Cut-off values of CYFRA and CRP were determined by receiver operating characteristic analyses. Prognostic values of age, stage, CYFRA and CRP were evaluated using multivariate analysis with a Cox proportional hazards model. RESULTS The median (range) values of CYFRA, and CRP were 4.1 (1.4–177.3) ng/mL and 0.2 (0–5.2) mg/dL, respectively. The median (range) age and follow-up period was 75 (64–86) years and 7.7 (1.1–29.9) months. Prognostic values of age (< 75 vs. ≥ 75), stage (non-metastatic vs. metastatic), CYFRA (cut-off 3.9 ng/mL) and CRP (cut-off 1.5 mg/dL) were evaluated dichotomously. Multivariate analyses revealed that p-values for age, stage and CRP is 0.83, 0.17, 0.48, respectively, and only CYFRA (P = 0.037) is a significant and an independent prognosticator. In 21 patients with metastatic disease (CYFRA cut-off 5.8 ng/mL), those with elevated CYFRA had 20.9-fold higher risk of cancer-specific mortality than those with non-elevated CYFRA. CONCLUSIONS The current results indicate that serum CYFRA level can be a prognosticator for patients with potentially lethal UUTC. Further prospective analyses will be needed to confirm our results. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e11-e12 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Yano More articles by this author Hironori Sugiyama More articles by this author Eiken Cho More articles by this author Hideki Takeshita More articles by this author Yohei Okada More articles by this author Hideki Nagamatsu More articles by this author Makoto Morozumi More articles by this author Satoru Kawakami More articles by this author Takumi Yamada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa

Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.

Abstract P2-01-13: Prognostic value of Circulating Tumor Cells count at progressive disease after first line chemotherapy metastatic breast patients in a large prospective multicenter trial including serum tumor markers (IC 2006–04 study)

Abstract Background: The IC 2006–04 study included prospectively 267 metastatic breast cancer patients before the start of first line chemotherapy. We previously reported and confirmed the prognostic and predictive of CTC counts before the start of treatment and after 3–4 &amp; 6–9 weeks of treatment (Pierga, JY SABCS 2010, Ann Oncol 2012). We report here the results of the last CTC count performed at tumor progression (i.e. end of first line chemotherapy). Methods: Patients were included in the study from 06/07 to 9/09. CTC were counted by the CellSearch® system at tumor progression (clinical and/or radiological progression). Results: 211 patients experienced a tumor progression at time of final data analysis and the planned CTC count has been performed in 61 patients. High CTC count (≥5 CTC/7.5ml) at progression was observed in 22 patients (36%) and was associated with elevated Cyfra 21–1 and ALP and was not associated with elevated CEA, CA 15–3, LDH, the elapsed progression-free survival, the onset of new metastasis. No CTC was detected at tumor progression in the 5 patients with HER2+ disease, in line with our previous results. The prognostic markers for overall survival at tumor progression were high CTC count (median overall survival 8 vs 19 months, p = .0006) and elevated Cyfra 21–1 (p = .001). Other serum markers (CEA, CA15-3, ALP, LDH) and tumor subtypes had no prognostic value at univariate analysis. At multivariate analysis, the two prognostic factors for overall survival were high CTC count (RR = 2.3 p = 0.03) and elevated Cyfra 21–1 (RR = 3.6 p = 0.02). Conclusion: In the prospective IC 2006–04 study, among the different markers tested at tumor progression during the first line chemotherapy for metastatic breast cancer, high CTC count and elevated Cyfra 21–1 levels were the only two independent prognostic markers for overall survival. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-13.

Detection of Urine Survivin in 40 Patients with Bladder Cancer

We investigated whether urine survivin, an inhibitor of the apoptosis protein, is useful for diagnosing bladder tumor. We measured urine survivin levels in 40 patients with bladder tumors and 9 healthy volunteers. The average urine survivin levels in the 40 patients and 9 healthy controls were not significantly different (3.802+/-8.669 and 1.127+/-1.529, respectively (p=0.3646) ). However, significantly high urine survivin levels were observed in 3 of the 40 patients, but not in healthy volunteers. Urine Cyfra 21-1 was not elevated (1.3 ng/ml) in one patient with a significantly elevated urine survivin level (33.54 ng/ml), while in two patients with elevated Cyfra (320 ng/ml and 240 ng/ml), the urine survivin level was not detectable. With improvements in the sensitivity of our Elisa system for urine survivin and combined use of urine Cyfra 21-1, it is possible that urine survivin will be a useful tumor marker in detecting both new-onset and recurrent bladder tumors.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer

Abstract.Gadducci A, Ferdeghini M, Cosio S, Fanucchi A, Cristofani R, Genazzani AR. The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1–51.4 ng/ml versus 0.4, 0.0–3.6 ng/ml,P&lt; 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P&lt; 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6–9.2 ng/ml versus 10.2, 0.1–51.4 ng/ml,P= 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3–40.7 ng/ml versus 0.4, 0.1–9.1 ng/ml,P&lt; 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Diagnostic Value of CYFRA 21–1 Tumor Marker and CEA in Pleural Effusion Due to Mesothelioma

The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas. We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients). CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays. The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%). This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Prognosis in bronchogenic squamous cell carcinoma groups divided according to serum squamous cell carcinoma-related antigen and cytokeratin 19 fragment levels

We examined differences in the 2-year survival rate in bronchogenic squamous cell carcinoma patients with normal serum levels of both cytokeratin 19 fragment (CYFRA 21-1) and squamous cell carcinoma-related antigen (SCC) (NL group, n=15), patients with only increased SCC levels (SCC+ group, n=14), patients with only increased CYFRA 21-1 levels (CYFRA+ group, n=14), and patients with elevated levels of both CYFRA 21-1 and SCC (EL group, n=65). The 2-year survival rates for the CYFRA+ and the EL group were lower than those for the SCC+ group and the NL group (0 and 12.9% vs. 66.7 and 85.6%, log rank: p<0.0001, Wilcoxon: p<0.0001). However, there were no differences between the rate for the SCC+ and the NL group and between that for the CYFRA+ and the EL group. Serum carcinoembryonic antigen (CEA) levels increased in the patients with the elevated CYFRA 21-1 levels. This results suggest that there may be some differences between squamous cell carcinoma patients with increased CYFRA 21-1 levels and those with normal levels and that it is CYFRA 21-1 levels, not SCC levels, that relate to the prognosis.

Comparison of Tumor Markers in Patients with Squamous Cell Carcinoma of the Head and Neck

The serum concentrations of three separate tumor markers, squamous cell carcinoma antigen (SCC Ag), carcinoembryonic antigen (CEA) and Cyfra 21-1 were clinically correlated in 86 randomly selected patients with squamous cell carcinoma involving the head and neck. Positive findings for each tumor marker were totalled and statistically analysed. The upper limits of normal for SCC Ag, CEA and Cyfra 21-1 were set at 1.5, 2.5 and 2.0 ng/ml, respectively. Positivity rates were 20.6% for SCC Ag, 14.0% for CEA and 41.7% for Cyfra 21-1. Elevated Cyfra 21-1 concentrations correlated somewhat with age, whereas elevated CEA levels correlated with the site of tumor involvement. Overall, Cyfra 21-1 appeared to be the most useful marker in head and neck squamous cell carcinoma.

CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Comparison of cytokeratin fragment 19 (CYFRA 21-1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) as tumour markers in bronchogenic carcinoma

To elevate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) and compare it with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) in bronchogenic carcinoma, the sera of 161 patients (58 with benign pulmonary disease and 103 with bronchogenic carcinoma) was investigated using immunoradiometric assay. Sensitivities for CYFRA 21-1, CEA and TPA (using 3·5 ng ml −1, 5·0 ng ml −1, 110 U 1 −1, respectively, cut-off values corresponding to a 95% specificity for benign pulmonary disease) in bronchogenic carcinoma were 64, 47 and 61%, respectively. Positive CYFRA 21-1 levels were identified in 75% of patients with squamous cell carcinoma ( n=36), in 67% with adenocarcinoma ( n=45), in 17% with large cell carcinoma ( n=6), and in 50% with small cell lung cancer (SCLC) ( n=16). However, CYFRA 21-1 levels were not significantly different between squamous cell carcinoma and the other histological types. The sensitivity of the combined measurement of CYFRA 21-1 with any other tumour marker was significantly higher than that of CYFRA 21-1 measurement alone. Elevated CYFRA 21-1 levels were observed in 44% of Stages I and II ( n=18) and 72% of Stages III and IV ( n=69) patients with non-small cell lung cancer ( P<0·05). A significant inter-marker correlation was observed between CYFRA 21-1 and TPA ( n=103, r=0·448, P<0·0001). Twenty-one patients were monitored by CYFRA 21-1, and significantly different changes in progressive patients ( P=0·0058) and regressive patients ( P=0·016) were obtained. These results indicate that CYFRA 21-1 may be not only a sensitive tumour marker in the diagnosis of bronchogenic carcinoma, but also a useful marker for the monitoring of bronchogenic carcinoma.

Does the assessment of serum markers in patients with lung cancer aid in the clinical decision making process?: Ebert W, Muley Th, Drings P. Thoraxklinik Heidelberg-Rohrbach, D-69126 Heidelberg. Anticancer Res 1996;16:2161–2168

This survey describes potential clinical applications of the tumour markers CYFRA 21-1, SCC antigen, NSE, and CEA in patients with lung cancer. Due to the rather low prevalence of bronchogenic carcinoma in the general public and the limited diagnostic accuracy, currently available tumour markers are unsuitable for the screening of asymptomatic individuals. All studies performed so far in patients with histologically confirmed NSCLC, agree that the best performance characteristics, in terms of sensitivity and specificity, were obtained with the CYFRA 21-1 test (sensitivity: 40-66%, specificity: 95% versus patients with benign pulmonary disorders) while NSE was found to be the marker of first choice in patients with SCLC (sensitivity: 77-85%). For diagnostic purpose, the value of tumour markers must be compared with the efficiency of standard clinical methods including imaging techniques and cytopathological examinations (detection rates: sputum cytology: 40-70%, biopsy at bronchoscopy in central tumours: 95-98%, biopsy at bronchoscopy + bronchial washing + thin needle aspiration in peripheral tumours: 85%). These figures show that the diagnostic yield of cytopathological examinations by far exceeds that of tumour markers. In addition, these investigations supply with histology and give informations on the T-stage (bronchoscopy). Tumour markers, however, may be used for diagnosis in advanced stages in which patients are very often not eligible for extensive investigations due to their performance status. In the differential diagnosis between NSCLC and SCLC a combination of CYFRA 21-1 and NSE was claimed to be helpful. It was demonstrated that 97% of patients could be correctly classified. NSE was shown to be useful to distinguish SCLC from malignant lymphoma, both the Hodgkin's (rate of false-positive elevations: 6.5%) and the non-Hodgkin's (rate of false positive elevations: 22.4%) types. By applying a cut-off point of NSE assays of 21.9 ng/ml corresponding to a 95% specificity versus the lymphoma group, SCLC is still indicated by elevated NSE levels with a sensitivity of 57.7%. Although a positive correlation of marker concentrations with increasing anatomical tumour extent could be demonstrated, the markers cannot be used for staging purposes due to a considerable overlap of marker levels between the individual stages. CYFRA 21-1 was shown to be unable to differentiate between operable (TNM I-IIIa) and inoperable (TNM IIIb/IV) NSCLC patients. The latter were identified with a detection rate of only 17% by the CYFRA 21-1 test (specificity 95% versus operable patients, cut-off point 20 ng/ml). Pretreatment-measured tumour markers, in particular CYFRA 21-1, were shown to provide prognostic information for the overall survival. The negative prognostic effect of CYFRA-21-1 was independent of classical prognostic markers such as performance status and tumour extent. There are several potential applications of serially-assessed tumour markers for disease monitoring of patients under therapy. In SCLC, increasing NSE levels within the remission phase were demonstrated to be strongly suggestive of tumour recurrence. This finding should give rise to further diagnostic procedures. NSE, however, was not able to differentiate between partial and complete remission since, in both cases, NSE levels dropped to the normal range; thus, NSE cannot replace clinical response evaluations. In NSCLC, it was found that curative surgery resulted in a significant drop of preoperatively elevated CYFRA 21-1 or SCC antigen levels down to the normal range. Although rising SCC antigen levels in the postoperative surveillance of patients with squamous cell carcinoma indicated very early tumour relapse, these results are of minor clinical utility due to the absence of curative therapy. Serial measurement of CYFRA 21-1 during chemotherapy in patients with inoperable squamous cell carcinoma has shown that there is a concordance of 74% between the course of the m

The clinical value of Cyfra 21-1 estimation for lung cancer patients.

Cytokeratin-19, one of the cytoskeletal proteins, is expressed both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 soluble fragment (Cyfra 21-1) measurement in lung cancer patients. Cyfra 21-1 levels were estimated in 35 patients (pts) with benign lung diseases and in 116 lung cancer patients: 55 pts with squamous cell lung cancer, 38 pts with small cell lung cancer and 23 pts with adenocarcinoma. The cutoff level was set at 4 ng/ml with a specificity of 94% and a sensitivity of 40%. Elevated Cyfra 21-1 values were found in 44% of squamous cell lung cancer, 39% of adenocarcinoma and 34% of small cell lung cancer pts (the difference was not significant). In squamous cell lung cancer and in adenocarcinoma elevated Cyfra 21-1 values were observed more often in patients with advanced disease than in patients with limited disease. There was no significant correlation between the initial Cyfra 21-1 level and the response to chemotherapy. Cyfra 21-1 was not a prognostic indicator, although in operable squamous cell lung cancer the proportion of survivors in the second year of observation was higher among the patients with normal preoperative Cyfra 21-1 levels.