Serum CYFRA Research Articles

P1-056 - Cytokeratin 19 Fragment (CYFRA21-1) Predicts the Efficacy of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) in Non-Small-Cell Lung Cancer (NSCLC) Harboring EGFR Mutation

ABSTRACT Background EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR-mutated patients treated with EGFR-TKIs. Methods We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with a high CYFRA21-1 level (>2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with a normal CYFRA21-1 level (median PFS 7.5 versus 14.0 months, P = 0.006). No significant difference in PFS was observed between the high CEA group (>5 ng/ml) and the normal CEA group (median PFS 8.6 versus 11.2 months, P = 0.2423). Multivariate analysis revealed that a high CYFRA21-1 level is independently associated with PFS (HR 1.35; P = 0.002) as well as squamous cell carcinoma (HR 1.40; P = 0.020) and performance status 2–4 (HR 2.63; P = 0.003). No statistically significant difference in overall survival (OS) was observed between the high CYFRA21-1 group and the normal group (median OS 24.8 versus 39.1 months, P = 0.104). Conclusions High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. The serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR-mutated patients can be divided into two subgroups according to the CYFRA21-1 level at initial diagnosis.

Serum cytokeratin 19 fragments: a dedifferentiation marker in advanced thyroid cancer

This study was undertaken to evaluate serum cytokeratin 19 fragment (Cyfra 21.1) expressions in patients with advanced thyroid carcinoma and to explore the relationship between serum Cyfra 21.1 and the degree of radioiodine ((131)I) avidity of thyroid carcinoma cells. Enrolled were 76 consecutive patients with advanced thyroid carcinoma submitted to high-activity (131)I treatment. In each patient, serum thyroglobulin (Tg) and Cyfra 21.1 were measured before (131)I administration and compared with the posttreatment whole-body scan results. Thirty-one (41%) of 76 patients had iodine-avid and 45 (59%) had iodine-refractory diseases respectively. Significantly higher serum Cyfra 21.1, but not Tg, levels were found in patients with (131)I-refractory disease compared with patients with iodine-avid disease (P<0.01). This is the first report describing the potential role of serum Cyfra 21.1 as marker of dedifferentiation and resistance to (131)I therapy in patients with advanced thyroid carcinoma.

1310P - Prognostic Impact of Serum Cyfra 21-1 In Advanced Lung Adenocarcinoma

ABSTRACT Background Serum CYFRA 21-1 is one of the most important serum markers in diagnosing non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. It is not known whether pretreatment serum CYFRA 21-1 values (PCV) have prognostic implications in advanced lung adenocarcinoma. The aim of this study was to evaluate the prognostic implications of PCV in advanced lung adenocarcinoma. Material and methods Out of 424 newly diagnosed lung cancer patients (pts) at our institution during the period April 2008- June 2010, we retrospectively reviewed 284 consecutive pts who were diagnosed with advanced lung adenocarcinoma and had been treated with systemic chemotherapy. Survival was estimated using the Kaplan-Meier method. A log-rank test was performed to test the significance of differences in the overall survival among the groups. A multivariate analysis using the Cox proportional hazards model was used to establish the association between various prognostic factors and survival. Results One hundred twenty one pts (43%) had activating EGFR mutations (Mt+) and 163 pts (57%) had EGFR wild type (Mt-). The median follow-up time was 29.7 months (range: 2.8- 75.7 months). In univariate analysis, gender (male/ female), ECOG performance status (PS) (0-2/ 3-4), PCV ( 2.2ng/ml), EGFR mutation (Mt + / Mt-), and smoking history (yes/ no) were favorable prognostic factors (p= 0.01, p 70], p = 0.67). A Cox's multivariate analysis showed that PCV ( 2.2ng/ml (n= 48) (median survival time [MST]: 52.4 vs. 21.0 months, p 2.2ng/ml (n = 86) (MST: 24.1 vs. 10.2 months, p Conclusions PCV should be regarded as a potential independent prognostic factor in both Mt+ and Mt- advanced lung adenocarcinoma. Disclosure All authors have declared no conflicts of interest.

Impact of serum biomarkers on esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (SCC) is frequently associated with a high mortality rate as a result of late diagnosis and/or aggressive behavior. Although multimodal treatment is applied for advanced tumors, many patients suffer from progressive disease and rapid recurrence. Besides various imaging techniques, serum biomarkers should also be useful for early diagnosing and treatment monitoring. A comprehensive review is provided here mainly on advancements of our clinical research in serum biomarkers to diagnose and/or monitor esophageal SCC. First, we focused on conventional secretory type serum markers, SCC-antigen and CYFRA 21-1. Both serum markers are useful to predict high-risk patients to develop recurrent disease. Second, we reviewed the clinicopathological significance of various angiogenic factors, vascular endothelial growth factor, thymidine phosphorylase, fibroblast growth factor, midkine, and hepatocyte growth factor. These growth factors could be useful biomarkers to predict lymph node and/or distant metastases. Finally, we reviewed advancements of clinical research on autoantibodies against tumor-specific antigens, particularly focused on serum p53 antibody. Because serum antibodies frequently respond to a small volume of tumors, they are useful in early tumor detection and prediction of residual cancer cells. Serum biomarkers may be a useful tool in the management of esophageal SCC.

Serum CYFRA 21-1 as a biomarker of pemetrexed plus cisplatin treatment in nonsquamous non-small cell lung cancer.

e18014 Background: Pemetrexed (P) is a key drug in the treatment of advanced non-squamous (N-Sq) non-small cell lung cancer (NSCLC). Although differential efficacies of P between squamous (Sq) and N-sq subtypes have been reported, it is difficult to get a clear histological diagnosis from a small biopsy sample. Therefore, a more objective, yet simple, biomarker for histology-based treatment is needed. Previously, we reported that serum Cytokeratin fragment 21-1 (CYFRA) was related to the outcome of P monotherapy. In this study, we examined whether serum CYFRA could predict the efficacy of the cisplatin-pemetrexed (CP) combination regimen as well as it did for P monotherapy. Methods: Pre-treatment serum concentrations of CYFRA, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and sialyl Lewis X-I antigen (SLX) were measured in 50 N-sq NSCLC patients who were enrolled in a phase II study of C (75 mg/m2 and 500 mg/m2) against N-Sq NSCLC. Eligibility criteria consisted of histologically or cytologically confirmed recurrent or metastatic N-Sq NSCLC previously untreated with chemotherapy, ECOG performance status (PS) 0-1. The primary endpoint was response rate, which was evaluated with RECIST. The planned sample size was 50 patients. We analyzed possible associations between these NSCLC marker levels and the efficacy of the CP regimen. Results: From April 2010 to June 2011, 50 N-sq NSCLC patients (male/female, 34/16; median age 60 y (28-74 y)) were enrolled in this study. Patients’ histological characteristics were: adeno/large/not otherwise specified (NOS), 39/5/6; PS: 0/1, 31/19. In these 50 patients, elevated levels of serum CYFRA, CEA, SCC and SLX were found in 25, 32, 5 and 32 patients, respectively. CYFRA was significantly associated with progression-free survival (PFS) (median PFS: 5.53 vs. 3.29 months; p &lt; 0.05), whereas no significant associations were observed between PFS and CEA, SCC or SLX. In addition, multivariate analysis showed that higher CYFRA and PS levels were significant factors associated with a shorter PFS. (p &lt; 0.05) Conclusions: Serum CYFRA is related to the outcome of CP treatment; our results suggest that serum CYFRA is a promising predictive marker of CP therapy.

Cytokeratin 19 fragment (CYFRA21-1) to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) harboring EGFR mutation.

10610 Background: EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR mutated patients treated with EGFR-TKIs. Methods: We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results: Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA21-1 level (&gt;2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with normal CYFRA21-1 level (median PFS 7.5 vs 14.0 months, p=0.006). No significant difference in PFS was observed between high CEA group (&gt;5 ng/ml) and normal CEA group (median PFS 8.6 vs 11.2 months, p=0.2423). Multivariate analysis revealed that high CYFRA21-1 level is independently associated with PFS (HR 1.35; p=0.002) as well as squamous cell carcinoma (HR 1.40; p=0.020) and performance status 2-4 (HR 2.63; p=0.003). No statistically significant difference in overall survival (OS) was observed between high CYFRA21-1 group and normal group (median OS 24.8 vs 39.1 months, p=0.104). Conclusions: High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. Serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR mutated patients can be divided into two subgroups according to CYFRA21-1 level at initial diagnosis.

Comparison of serum CYFRA 21-1 and ROMA in distinguishing ovarian cancer from benign pelvic masses.

e15565 Background: CYFRA 21-1 is a known lung cancer biomarker. In subjects with ovarian cancer (OC) versus those with benign gynecological diseases, serum CYFRA 21-1 was reported sensitivities (SN) of 44% and 41% at specificity (SP) of 95% for OC detection using an ELISA assay by Hasholzner U (1994) and Tempfer C (1998), respectively. Nolen B (2010) reported a SN of 84.1% and 85.8% and a SP of 85% and 79.3% with a combination of CYFRA 21-1, CA 125 and HE4 using a multiplex bead-based immunoassay in a training and validation set, respectively. We carried out a cohort study to evaluate the serum CYFRA 21-1 as an ovarian cancer biomarker and compared it with ROMA (Risk of Ovarian Malignancy Algorithm), an FDA-cleared ovarian cancer algorithm. Methods: ARCHITECT CYFRA 21-1 assay was used to measure the levels of serum CYFRA 21-1. Single point serum samples from 170 female subjects with a pelvic mass were randomly selected from an archive cohort of female subjects. Among the 170 subjects, 47 had OC (42 with epithelial OC and 5 with low malignant potential tumor) and 123 with benign gynecological diseases. ROMA values were obtained with HE4 EIA and ARCHITECT CA 125 II. Results: For ARCHITECT CYFRA 21-1, the ROC-AUC, cut-off, SN, SP, PPV and NPV were 86%, 1.8 ng/mL, 70.2% (95% CI: 55.1% to 82.7%), 95.1% (95% CI: 89.7% to 98.2%), 84.6% and 89.3%, repectively. For ROMA algorithm, the ROC-AUC, cut-off, SN, SP, PPV and NPV were 92%, 2.44, 89.4% (95% CI: 76.9% to 96.5%), 84.6% (95% CI: 76.9% to 90.4%), 68.9% and 95.4%, repectively. Chi-square test showed an SN for ROMA was significantly higher than that of ARCHITECT CYFRA 21-1 (p &lt; 0.05), and SP for ARCHITECT CYFRA 21-1 was significantly higher than that of ROMA (p &lt; 0.01). Conclusions: In distinguishing OC from benign gynecological diseases, ROMA algorithm appears to be more sensitive than serum ARCHITECT CYFRA 21-1 (p &lt; 0.05), and serum ARCHITECT CYFRA 21-1 appears to be more specific than (p &lt; 0.01) in this cohort study.

Abstract 3574: Detection of serum CYFRA 21-1 as a biomarker for stratification of ovarian cancer risk in women with a pelvic mass

Abstract CYFRA 21-1 is a known lung cancer biomarker. In subjects with ovarian cancer (N = 159) and those with benign gynecological diseases (N = 53), serum CYFRA 21-1 reported a sensitivity (SN) of 44% and a specificity (SP) of 95% for ovarian cancer detection at a cut-off value of 2.4 ng/mL using an ELISA assay (Hasholzner U, et al, 1994). Another report showed a SN of 41% and a SP of 95% for ovarian cancer (N = 37) versus benign ovarian cysts, endometriosis, pelvic inflammatory disease, bowel disease and liver cirrhosis (N = 168) using an ELISA assay (Tempfer C, et al, 1998). We carried out a pilot study to evaluate the serum CYFRA 21-1 as a biomarker for stratification of ovarian cancer risk in women with a pelvic mass. Methods: ARCHITECT CYFRA 21-1 was used to measure the levels of serum CYFRA 21-1. Single point frozen serum samples from 171 female subjects with a pelvic mass were randomly selected from the archive clinical trial described by Moore R et al (2009). Of the 171 subjects, 42 had epithelial ovarian cancer (EOC), 5 with low malignant potential tumor (LMP) and 124 with benign pelvic masses. Results: To stratify EOC from benign pelvic masses and LMP, the following performance was obtained for serum CYFRA 21-1: Notes: The cutpoints were set at 1.2 and 1.8 ng/mL to reach a 75% and 95% SP, respectively. Conclusion: Serum CYFRA 21-1 appears to be a useful biomarker for stratification of EOC from benign pelvic mass and LMP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3574. doi:1538-7445.AM2012-3574

CYFRA 21-1 as a Prognostic and Predictive Marker in Advanced Non–Small-Cell Lung Cancer in a Prospective Trial: CALGB 150304

Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may be associated with response to therapy and survival in non-small-cell lung cancer (NSCLC). As a prospective correlative study of Cancer and Leukemia Group B 30203, a randomized phase II trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton, or both) in advanced NSCLC, serum CYFRA levels were obtained before and during treatment. Serum CYFRA levels were measured at baseline and after the first cycle of treatment using an electrochemoluminescent assay. Paired specimens were available from 88 patients. The logarithms of the initial concentration and of the difference in concentrations were analyzed for association with overall survival (OS) and failure-free survival (FFS). Lower baseline CYFRA levels were associated with both longer OS and FFS (p < 0.0001 and p = 0.0003). In addition, larger reductions in CYFRA levels correlated with longer OS and FFS (p = 0.0255 and p = 0.0068). CYFRA and change in CYFRA were found to be reliable markers for response to chemotherapy for NSCLC; however, a precise threshold to mark response has yet to be determined.

The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer

Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

Prognostic Significance of CYFRA21-1, CEA and Hemoglobin in Patients with Esophageal Squamous Cancer Undergoing Concurrent Chemoradiotherapy

To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

Clinical Usefulness of CEA, CA19-9, and CYFRA 21-1 as Tumor Markers for Urothelial Bladder Carcinoma

Objective: To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Materials and Methods: Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. Results: A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p < 0.01) and higher grade (p < 0.05). In contrast, serum CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p < 0.01). Patients who were positive for CYFRA 21-1 had significantly worse disease-specific survival (p < 0.0001, log rank test). Conclusion: Serum CYFRA 21-1 seems to be a marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated.

Serum Tumor Markers CEA, CYFRA21-1, and CA-125 Are Associated With Worse Prognosis In Advanced Non–Small-Cell Lung Cancer (NSCLC)

BackgroundSerum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Patients and MethodsTwo hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. ResultsBaseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P < .05). PFS in patients with elevated CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P < .05). The OS in patients with high and normal levels of tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P < .001). ConclusionIn our analysis, high levels of tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients.

Editorial Comment to Prognostic impact of preoperative serum CYFRA 21‐1 in patients with upper urinary tract urothelial carcinoma

Upper urinary tract urothelial carcinoma represents an infrequently diagnosed malignancy accounting for 8% of overall urothelial tumors. Its prognosis has been reported to be poorer than urothelial bladder cancer and has been predominantly associated with pathological stage and grade.1 Although several tissue biomarkers have already been investigated with respect to survival,2,3 the necessity of defining an easily used, reliable tool detected in serum or urine samples still remains. In this regard, the study by Suyama et al., which renders CYFRA 21-1 a survival prognosticator, is of great interest.4 It is the first report that shows a correlation between this specific serum marker and survival rate in patients with upper tract urothelial cancer. The authors evaluated 45 individuals with ureteral and pelvicalyceal tumors. They found that patients with high (≥2.7 ng/mL) CYFRA 21-1 levels had a statistically worse prognosis than those with low (<2.7 ng/mL) pretreatment concentrations. Although the reported number of patients was limited and the median follow-up period was rather short (14.4 months) to extract safe conclusions, it seems that CYFRA 21-1 could serve as a promising marker in terms of survival prognosis. It is widely accepted that, from the diagnosis point of view, we afford reliable methods in detecting upper urinary tract urothelial cancer. Computed tomography and flexible ureterorenoscopy are accompanied by sensitivity and specificity of over 95%.5,6 However, we need prognostic predictors, particularly in cases where nephroureterectomy is not the first treatment option and, thus, thorough pathological examination cannot be available. In fact, the only reported serum independent survival indicator thus far has been C-reactive protein.7 In view of this, the authors are to be congratulated for their concept. CYFRA 21-1 might be used in the future as a survival-related parameter, though not before large patient cohorts and long follow-up periods confirm its accuracy and establish its role.

Prognostic significance of preoperative serum CYFRA 21‐1 in patients with upper urinary tract urothelial carcinoma

The prognosis for upper urinary tract urothelial carcinoma is generally poorer than that for bladder cancer, and prognostic predictors with a high specificity for upper urinary tract urothelial carcinoma (UUT-UC) are needed to optimize treatment. In fact, the only preoperative predictor currently available is C-reactive protein. In the present study, we investigated the usefulness of pretreatment serum CYFRA 21-1 as a new prognostic predictor in UUT-UC. A total of 45 UUT-UC patients for whom serum CYFRA 21-1 was measured before treatment were included in this retrospective analysis. Patients were separated into high and low serum CYFRA 21-1 groups based on a cut-off value of 2.7 ng/mL determined from a receiver operating characteristic curve. Kaplan-Meier survival curves were calculated and the overall survival rate was statistically analyzed for the high and low pretreatment serum CYFRA 21-1 groups using the log-rank test. Multivariable analysis was carried out using the Cox proportional hazards analysis. By the median follow-up period of 14.4 months, 20 patients (44.4%) had died. Of the 45 patients, 23 (51.1%) were in the high pretreatment serum CYFRA 21-1 group, and the overall survival rate of this group was significantly lower (P < 0.001). Multivariable analysis identified only distant metastasis (P < 0.001) and pretreatment serum CYFRA 21-1 (P = 0.039) as independent prognostic predictors. Distant metastasis did not significantly differ between the two groups or correlate with pretreatment serum CYFRA 21-1. These findings suggest that pretreatment serum CYFRA 21-1 values could serve as a prognostic predictor of UUT-UC.

Clinical value of CEA and CYFRA21-1 as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer patients

To investigate the value of carcinoembryonic antigen (CEA) or cytokeratin 19 fragment (CYFRA21-1) as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients. 228 cases of advanced NSCLC with chemotherapy were enrolled into this retrospective study. The serum CEA or CYFRA21-1 levels of all patients were above the cut-off limit before treatment. The relationship between changes of tumor markers (TMs) and imaging therapeutic efficacy or progression-free survival (PFS) was analyzed, and the value of TMs in therapeutic efficacy assessment was evaluated. According to RECIST criteria, partial response (PR) occurred in 40 cases, stable disease (SD) in 151 and PD (progressive disease) in 37. The cut-off values of the changes of TMs between pre- and post-treatment were determined according to the above mentioned criteria. The CEA down (D), stable (S), above (A) groups were 90, 49 and 66 cases, respectively. CYFRA21-1 down (D), stable (S), above (A) groups were 84, 26 and 37 cases, respectively. PR groups were 68.4% and 88.9% in CEA and cyfra21-1 down groups, respectively, 7.9% and 5.6% in the above groups, respectively. PD groups were 59.4% and 76.2% in CEA and CYFRA21-1 above groups, respectively. No PD cases were in the down groups. The changes of TMs in SD group were between them. Statistically significant correlations were observed between changes of TMs and imaging therapeutic efficacy (r(CEA) = 0.45, P = 0.00; r(CYFRA21-1) = 0.44, P = 0.00). PFS among different TMs groups were significantly different (all P < 0.05), which can be used to further distinguish the prognosis among SD subgroups. Changes of TMs can be used to predict the imaging therapeutic effect and PFS of the patients, and if the SD group is divided into subgroups according to different therapeutic efficacy and prognosis, it may help the patients to receive individualized treatment.

Clinical significance of serum cytokeratin 19 fragment in the prediction of chemotherapy efficacy and prognosis in patients with advanced non-small cell lung cancer

背景与目的由于RECIST（Response Evaluation Criteria in Solid Tumors, RECIST）标准不能对存活肿瘤组织进行检测，也不能对所有无法测量病灶的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的疗效进行准确评估，本研究通过检测进展期NSCLC患者化疗前后血清细胞角蛋白19片段（cytokeratin 19 fragment, CYFRA21-1）表达水平的变化以评价其在预测进展期NSCLC患者化疗疗效及预后中的临床价值。方法采用全自动生化分析仪电化学发光免疫法检测112例初治的NSCLC患者化疗前和化疗2周期后血清CYFRA21-1表达水平的变化，应用受试者特征工作曲线（receiver operating characteristics curve, ROC）评价血清CYFRA21-1反应在诊断影像学缓解（objective response, OR）中的效能及其与预后的相关性。结果经一线铂类为基础的两药联合方案化疗2周期后，血清CYFRA21-1水平较化疗前基线水平明显下降。80例可评价影像学和血清学疗效的患者中，26.3%（21/80）的患者达到影像学OR。化疗2周期后40.0%（32/80）的患者血清CYFRA21-1水平下降≥60%（血清CYFRA21-1反应）。血清CYFRA21-1反应与影像学OR之间有明显的统计学相关性（P < 0.001）。所有患者的中位生存期为9.9个月，血清CYFRA21-1水平下降≥60%患者的生存期明显长于CYFRA21-1水平下降 < 60%的患者（12.3个月vs 8.9个月，P < 0.001）。单因素分析结果显示，血清CYFRA21-1基线水平、CYFRA21-1反应、PS评分及影像学OR是影响生存期的重要预后因素。Cox多因素生存分析证实，仅血清CYFRA21-1基线水平、CYFRA21-1反应及PS评分是影响预后生存期的独立因素，而OR则与预后无关。结论血清CYFRA21-1水平可敏感地反映影像学肿瘤体积大小的变化，可能是评价进展期NSCLC患者化疗疗效的替代指标，同时也是预测预后生存期的可信指标。

Serum CYFRA21-1 as a prognostic marker for patients with undifferentiated nasopharyngeal carcinoma

The purpose of this study was to evaluate the potential of serum CYFRA21-1 and carcinoembryonic antigen (CEA) as prognostic markers in patients with undifferentiated nasopharyngeal carcinoma. Sixty-one patients who received definitive radiotherapy/chemoradiotherapy were analysed retrospectively. We investigated the association of the follow-up results with pretreatment level, post-treatment level and change of serum CYFRA21-1 and CEA, respectively. Patients with low pretreatment CYFRA21-1 had a significantly better overall survival. There were no significant associations among the remaining serum markers, and the survival and recurrence rates on multivariate analysis. The present study shows that pretreatment CYFRA21-1 level is a potential factor for predicting long-term survival.

Clinical value of serum TPS, CEA, Pro-GRP and CYFRA21-1 in patients with lung cancer

背景与目的血清肿瘤标志物在肺癌的诊断、疗效、预后判断中起着重要作用。本研究探讨血清组织多肽特异性抗原（tissue polypeptide specifc antigen, TPS）与癌胚抗原（carcinoembryonic antigen, CEA）、胃泌素释放肽前体（precursor of gastrin-releasing peptide, Pro-GRP）和细胞角蛋白19片段（cytokeratin-19-fragments, CYFR21-1）的水平及其在肺癌患者中的临床意义。方法应用ELISA检测82例肺癌患者化疗前及部分患者化疗后4种标志物水平。结果肺癌患者TPS、CEA、Pro-GRP阳性率及水平显著高于肺部良性疾病组和健康对照组。广泛期小细胞肺癌患者TPS阳性率显著高于局限期患者。患者化疗后TPS、CEA、Pro-GRP阳性率及水平均显著下降。非小细胞肺癌患者TPS水平是预后的独立因素。结论TPS在肺癌患者的辅助诊断、疗效观察有较好的临床意义，对非小细胞肺癌的预后判断方面可能有一定价值。

Declines in serum CYFRA21-1 and carcinoembryonic antigen as predictors of chemotherapy response and survival in patients with advanced non-small cell lung cancer

The aim of this study was to investigate the clinical value of serum cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in the prediction of chemotherapy response and prognosis in patients with advanced non-small cell lung cancer (NSCLC). Serum CYFRA21-1 and CEA levels of 98 patients with advanced NSCLC were measured using immunoradiometric kits prior to and after 2 cycles of chemotherapy. After 2 cycles of chemotherapy, 45 patients achieved a radiological objective response (OR), 30 patients achieved stable disease (SD) and 23 patients had progressive disease (PD). Serum CYFRA21-1 and CEA were significantly decreased compared to baseline levels (P<0.001). By ROC curve analysis, a ≥60% reduction in CYFRA21-1 and a ≥25% reduction in CEA were the optimal cut-off levels with best sensitivity and specificity for the diagnosis of radiologic OR. The median survival of all patients was 10.2 months (range 2.6-26.3). Univariate survival analysis showed that the Eastern Cooperative Oncology Group (ECOG) performance status (PS) score, radiologic OR, a ≥60% reduction in CYFRA21-1 and a ≥25% reduction in CEA were significant prognostic factors for better overall survival. The median overall survival time in patients with a ≥60% reduction in CYFRA21-1 was significantly longer than in those with a <60% reduction (P<0.001). Similarly, the median overall survival time in patients with a ≥25% reduction in CEA was also significantly longer than in those with a <25% reduction (P<0.001). Multivariate analysis showed that ECOG PS score, a ≥60% reduction in CYFRA21-1 and a ≥25% reduction in CEA were independent prognostic factors of survival, while radiologic OR was not. In conclusion, a ≥60% reduction in CYFRA21-1 and a ≥25% reduction in CEA may be reliable surrogate markers for the prediction of chemothrapy response and prognosis, especially for the diagnosis of radiologic OR.