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BackgroundThis meta-analysis evaluated whether pretherapy serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) are predictive of response to therapy in non-small cell lung cancer (NSCLC) and whether changes in these markers during vs pretherapy are indicative of response.MethodsOriginal peer-reviewed studies enrolling adults with untreated advanced NSCLC were identified using PubMed. Two reviewers independently extracted data from eligible studies and assessed study heterogeneity and the risk of study bias.ResultsFourteen studies were eligible; 11 had objective response as an end point and three evaluated clinical benefit (i.e., response and stable disease). Study bias was relatively low. Both markers showed comparable modest predictive value across studies, with baseline CYFRA 21-1 numerically better in predicting treatment benefit. A good performance in identifying objective response during treatment was seen (AUC 0.724 (95% CI 0.667-0.785) for CYFRA 21-1 and 0.728 (95% CI, 0.599-0.871) for CEA). A decline in CYFRA 21-1 levels during treatment was highly indicative for objective response (sensitivity 79.1% (95% CI 71.5-85.1)).ConclusionsComprehensive analysis of study heterogeneity and bias provides a high level of evidence for the clinical utility of CEA and CYFRA 21-1 for the prediction and monitoring of response in NSCLC.

BACKGROUND: Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice. OBJECTIVE: To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes. METHODS: Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed. RESULTS: CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76–0.87), 0.78 (0.73–0.84), and 0.88 (0.84–0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90–0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81–0.91), 0.80 (0.74–0.85), and 0.85 (0.79–0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89–0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84–0.94) and 0.96 (0.93–0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95–0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81–0.91), NSE (AUC 0.83; 0.78–0.88) and CYFRA 21-1 (AUC 0.69; 0.64–0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91–0.96), with a sensitivity of 88% at 90% specificity. CONCLUSIONS: The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Therapeutic possibilities for non-small cell lung cancer (NSCLC) have considerably increased during recent decades. OBJECTIVE: To summarize the prognostic relevance of serum tumor markers (STM) for early and late-stage NSCLC patients treated with classical chemotherapies, novel targeted and immune therapies. METHODS: A PubMed database search was conducted for prognostic studies on carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase, squamous-cell carcinoma antigen, progastrin-releasing-peptide, CA125, CA 19-9 and CA 15-3 STMs in NSCLC patients published from 2008 until June 2022. RESULTS: Out of 1069 studies, 141 were identified as meeting the inclusion criteria. A considerable heterogeneity regarding design, patient number, analytical and statistical methods was observed. High pretherapeutic CYFRA 21-1 levels and insufficient decreases indicated unfavorable prognosis in many studies on NSCLC patients treated with chemo-, targeted and immunotherapies or their combinations in early and advanced stages. Similar results were seen for CEA in chemotherapy, however, high pretherapeutic levels were sometimes favorable in targeted therapies. CA125 is a promising prognostic marker in patients treated with immunotherapies. Combinations of STMs further increased the prognostic value over single markers. CONCLUSION: Protein STMs, especially CYFRA 21-1, have prognostic potential in early and advanced stage NSCLC. For future STM investigations, better adherence to comparable study designs, analytical methods, outcome measures and statistical evaluation standards is recommended. [ABSTRACT FROM AUTHOR]

BACKGROUND: Serum tumor markers (STM) may complement imaging and provide additional clinical information for patients with non-small cell lung cancer (NSCLC). OBJECTIVE: To determine whether STMs can predict outcomes in patients with stable disease (SD) after initial treatment. METHODS: This single-center, prospective, observational trial enrolled 395 patients with stage III/IV treatment-naïve NSCLC; of which 263 patients were included in this analysis. Computed Tomography (CT) scans were performed and STMs measured before and after initial treatment (two cycles of chemotherapy and/or an immune checkpoint inhibitor or tyrosine kinase inhibitor); analyses were based on CT and STM measurements obtained at first CT performed after cycle 2 only PFS and OS were analyzed by Kaplan-Meier curves and Cox-proportional hazard models. RESULTS: When patients with SD (n = 100) were split into high- and low-risk groups based on CYFRA 21-1, CEA and CA 125 measurements using an optimized cut-off, a 4-fold increase risk of progression or death was estimated for high- vs low-risk SD patients (PFS, HR 4.17; OS, 3.99; both p < 0.0001). Outcomes were similar between patients with high-risk SD or progressive disease (n = 35) (OS, HR 1.17) and between patients with low-risk SD or partial response (n = 128) (PFS, HR 0.98; OS, 1.14). CONCLUSIONS: STMs can provide further guidance in patients with indeterminate CT responses by separating them into high- and low-risk groups for future PFS and OS events. [ABSTRACT FROM AUTHOR]

Tumor marker determinations are valuable tools for the guidance of breast cancer patients during the course of disease. They are assessed on diverse analytical platforms that may be associated with differences according to the methods applied and the clinical performance. To investigate the method dependency and clinical significance of breast cancer protein tumor markers, CEA, CA 15-3, CA 125, CA 19-9 and AFP were measured in a total of 154 biobanked samples from 77 patients with breast cancer, 10 with DCIS, 31 with benign breast diseases and 36 healthy controls using a Millipore multiplex biomarker panel (MP) and an automized version of the routinely used Vista LOCI technology. The markers were compared between methods and investigated for diagnostic performance. CEA, CA 15-3 and AFP showed good correlations between both platforms with correlation coefficients of R = 0.85, 0.85 and 0.92, respectively, in all samples, but similarly also in the various subgroups. CA 125 and CA 19-9 showed only moderate correlations (R = 0.71 and 0.56, respectively). Absolute values were significantly higher for CEA, CA 15-3, CA 125 and AFP in the Vista LOCI as compared with the MP method and vice versa for CA 19-9. The diagnostic performance for discrimination of breast cancer from healthy controls was similar for both methods with AUCs in ROC curves for CEA (MP 0.81, 95% CI 0.72–0.91; LOCI 0.81; 95% CI 0.72–0.91) and CA-15-3 (MP 0.75, 95% CI 0.65–0.86; LOCI 0.67, 95% CI 0.54–0.79). Similar results were obtained for the comparison of breast cancer with benign breast diseases regarding CEA (AUC MP 0.62, 95% CI 0.51–0.73; LOCI 0.64, 95% CI 0.53–0.74) and CA-15-3 (MP 0.70, 95% CI 0.6–0.81; LOCI 0.66, 95% CI 0.54–0.77). Both platforms show moderate to good method comparability for tumor markers with similar clinical performance. However, absolute levels in individual patients should be interpreted with care. [ABSTRACT FROM AUTHOR]

The glycoproteins alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have long been approved as biomarkers for diagnosing and monitoring tumors. International Reference Preparations (IRPs) have been around since 1975. Nevertheless, manufacturer-dependent differences have been reported, indicating a lack of harmonization. This paper analyzes data from 15 external quality assessment (EQA) surveys conducted worldwide between 2018 and 2022. The aim was to gain insight into the longitudinal development of manufacturer-dependent differences for CEA and AFP. In each survey, participating laboratories received two samples with different tumor marker levels. Inter- and intra-assay variability was analyzed and the mean 80% and 90% of the manufacturer collectives were compared to the evaluation criteria of the German Medical Association (RiliBÄK). The median EQA results for CEA revealed manufacturer-dependent differences between the highest and lowest collective of up to 100%; for AFP, the median differences mostly remained below 40%. The coefficients of variation were predominantly low for both markers. We concluded that the current assays for AFP and CEA detection are better harmonized than previously reported. The assays displayed a good robustness; however, a narrowing of the current assessment limits in EQA schemes could further enhance the quality of laboratory testing. [ABSTRACT FROM AUTHOR]

Differential diagnosis of suspicious lung masses is essential for the selection of the appropriate therapy strategy. While non-small cell lung cancer (NSCLC) in early stages and single lung metastases from other cancers mostly are resected by surgery, late stage NSCLC, small cell lung cancers (SCLC) and multiple lung metastases are treated by systemic chemo- and/or radiotherapeutic approaches. In many patients, biopsies for the histopathological subtyping can not be taken due to multimorbidity and instable clinical conditions of the patient or unfavourable localisation of the tumor. In addition, heterogeneity of lung tumors may imply the presence of different malignant cell types in one suspicious lesion. As tumor-related biomarkers in blood reflect the biochemical properties of cancer cells, their release or non-release may be helpful to support the clinical decision making. This review summarizes the current knowledge about the potential and the role of serum-based biomarkers for the differential diagnosis of lung cancer which is also mirrored in the new recommendations of the National Academy of Clinical Biochemistry (NACB). [ABSTRACT FROM AUTHOR]

Prognostic information on the course of cancer disease is highly relevant for the accurate decision of the most effective treatment strategy for an individual patient. In early stage disease, the application of adjuvant chemo- or radiotherapy after surgery depends on the risk of the patient to early suffer from tumor recurrence. In advanced stage disease, risk stratification of the patients influences the choice of more aggressive or mild therapy alternatives. Besides tumor related parameters like tumor stage and individual factors, additional information by biomarkers is needed to better characterize patients prognosis in both situations. Although there are plenty of studies dealing on the prognostic relevance of diverse biomarkers in non-small cell lung cancer (NSCLC), the results are quite heterogeneous and sometimes conflicting. Reasons for this situation may be found in the design, the performance, the evaluation and the quality of result reporting of the studies. In this review, we focus on the prerequisites of informative prognostic trials, spot on the general shortcomings of studies published so far, and summarize the results of the prognostic studies available for early and advanced stages of NSCLC. [ABSTRACT FROM AUTHOR]

The article looks at developments in the study of lung cancer biomarkers. According to the authors, circulating biochemical markers are important and informative tools for managing lung cancer. Biomarkers are considered vital for follow-up investigations because biochemical changes in the blood manifest early the possibility of increasing tumor activity. Information on the release of biochemical markers by various benign and malignant diseases has been limited.

As the release and amount of circulating biomarkers show considerable variations between individuals, single value determinations are often difficult to be interpreted on their diagnostic or prognostic significance on the individual level. However, changes of the biomarker levels in a specific person during the disease course are quite informative for the estimation of the efficacy of therapy or the early detection of recurrent disease because they consider only intraindividual variations. If methods for marker determination are maintained, preanalytical and analytical standard prerequistits are respected, thresholds for each marker have to be defined which exceeds the normal, intraindividual biological variation. Then continuous biomarker increases may be indicative for disease activity in terms of inefficient therapy response or tumor recurrence while decreasing values often are associated with activity reduction of cancer disease. Here, we review the current knowledge on biomarker kinetics in patients with non-small cell lung cancer (NSCLC) and discuss the conditions and pitfalls of their relevance for the estimation efficacy of therapy and the early detection of recurrent disease. Further, we suggest a scenario to reveal the power of the defined biomarker use in future and to include those markers into the individual management of NSCLC patients. [ABSTRACT FROM AUTHOR]

Apoptotic markers and tumor-associated antigens might be suitable to indicate the response to radiochemotherapy early. We analyzed the courses of nucleosomes, CEA, CA 19-9 and CYFRA 21-1 in 25 colorectal cancer patients during radiochemotherapy (4 postoperative, 13 preoperative, 8 local relapse therapy). Blood was taken before therapy, daily during the first week, once weekly during the following weeks, and at the end of the radiochemotherapy. After a temporary decline 6 h after the first irradiation, nucleosomes rose in most patients rapidly reaching a maximum during the first days which was followed by a subsequent decrease. In patients receiving postoperative therapy after complete resection of tumor, nucleosome levels generally were lower than in patients with preoperative or relapse therapy. Correspondingly, CEA, CA 19-9 and CYFRA 21-1 levels of postoperatively treated patients were the lowest whereas those with tumor relapse had the highest ones. During preoperative therapy, lower nucleosome concentrations were found in patients with response to therapy resulting in a smaller area under the curve of days 1–3 (AUC) than in those with progressive disease (p = 0.028). The other parameters did not indicate the response to therapy at the initial treatment phase. In conclusion, the course of nucleosomes (AUC) might be valuable for the early prediction of therapy response in preoperatively treated colorectal cancer patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]