To investigate the correlations between metabolic parameters (MPs) of 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT), serum tumor markers (STMs), and tumor mutational burden (TMB) in patients with non-small cell lung cancer (NSCLC).
In this retrospective study, we enrolled 129 patients with NSCLC (males, 78; females, 51) who underwent baseline TMB and STM tests and 18 F-FDG PET/CT scans before treatment between March 2018 and September 2022. Patients were categorized into TMB-high (TMB ≥10 mutations/Mb; n = 27 [20.9%]) and non-TMB-high (TMB <10 mutations/Mb; n = 102 [79.1%]) groups. Binary logistic regression analyses were performed to determine independent predictors of TMB-high. Univariate and multivariate linear regression analyses were performed to determine independent predictors of TMB level on a log scale. Subgroup analyses for adenocarcinoma (ADC), ADC with EGFR+, ADC with EGFR-, and squamous cell carcinoma (SCC) were performed.
For ADC, all MPs (SULpeak , SULmax , SULmean , MTV, and TLG) were significantly higher in the TMB-high group than the non-TMB-high group; smoker (odds ratio [OR] = 27.08, p = 0.018), EGFR+ (OR = 0.03, p = 0.033), KRAS+ (OR = 7.98, p = 0.083), high CEA (OR = 33.56, p = 0.029), and high CA125 (OR = 13.68, p = 0.030) were independent predictors of TMB-high; and all MPs showed significant positive linear correlations with TMB on a log scale, with SULpeak as an independent predictor. However, no significant correlation was observed for SCC.
MPs and STMs can predict the TMB level for patients with ADC, and may serve as potential substitutes for TMB with increased value and easy implementation in guiding immunotherapy through noninvasive methods.

Metastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels.
A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen\'s kappa.
A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow-up data points. By using pre-orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy-two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen\'s kappa was 0.69 (p < 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 72 patients or undertreatment of 34 patients.
The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients.

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignant skin adnexal tumor. Recurrences are most often localized, and long-term follow-up after complete surgery consists essentially of self-examination of skin. We report one case of metastatic PCMC with elevated levels of serum CEA and CA15.3. Because of the difficulty to differentiate PCMC and metastasis of mucinous breast cancer, the hypothesis of a metastasized breast cancer was ruled out. These tumor markers contributed to the monitoring of the metastatic disease. Since metastatic disease was diagnosed after several years of seeming complete remission, CEA and CA15.3 would likely have allowed the clinicians to detect the relapse earlier. Although the use of tumor biomarkers in PCMC is not rooted in clinical practice and not mentioned in guidelines, we suggest that CEA and CA15.3 could be of particular interest to monitor and detect early metastatic PCMC.

UNASSIGNED: Gastric cancer (GC) is one of the most common malignant tumors in humans. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 are all serum tumor markers for diagnosis of gastric cancer. However, the results of studies reporting the diagnosis of the combined three varied. In this study, the combined diagnostic performance of these 3 serum tumor markers was systematically evaluated.
UNASSIGNED: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang data were searched for literature on serum tumor markers CEA, CA19-9, and CA72-4 in the diagnosis of gastric cancer. The inclusion criteria were designed according to the Participants, Intervention, Control, Outcomes, Study (PICOS) principles. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scoring scale was used to assess the quality of the literature. After extracting the data, Stata 16.0 software was used for meta-analysis.
UNASSIGNED: A total of 10 articles were finally included, and a total of 6,574 patients participated in diagnosis, 3,077 for confirmed GC and 3,497 for non-GC respectively. Meta-analysis results showed that the diagnostic sensitivity of the combined diagnosis of the 3 tumor markers was 0.67 [95% confidence interval (CI): 0.54, 0.77], the specificity was 0.89 (95% CI: 0.82, 0.93), the positive likelihood ratio was 5.9 (95% CI: 3.5, 9.8), the negative likelihood ratio was 0.38 (95% CI: 0.27, 0.53), and the diagnostic odds ratio (DOR) was 16 (95% CI: 8, 32). The diagnostic sensitivity of CA72-4 diagnosis alone was 0.58 (95% CI: 0.40, 0.73), specificity was 0.86 (95% CI: 0.80, 0.90), the positive likelihood ratio was 4.0 (95% CI: 3.1, 5.1), the negative likelihood ratio was 0.49 (95% CI: 0.34, 0.71), and the DOR was 8 (95% CI: 5, 14). The area under the ROC curve (AUC) values of the combined three diagnosis and CA72-4 diagnosis alone were 0.87 (95% CI: 0.83, 0.89) and 0.84 (95% CI: 0.81, 0.87), respectively, the difference was statistically significant (Z=4.86, P<0.05).
UNASSIGNED: The combined use of the 3 tumor markers has higher sensitivity and specificity than single marker diagnosis in the diagnosis of gastric cancer.

BACKGROUND: The widespread introduction of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) has led to durable responses but still many patients fail and are treated beyond progression.
OBJECTIVE: This study investigated whether readily available blood-based tumor biomarkers allow accurate detection of early non-responsiveness, allowing a timely switch of therapy and cost reduction.
METHODS: In a prospective, observational study in patients with NSCLC treated with nivolumab or pembrolizumab, five serum tumor markers were measured at baseline and every other week. Six months disease control as determined by RECIST was used as a measure of clinical response. Patients with a disease control <  6 months were deemed non-responsive. For every separate tumor marker a criterion for predicting of non-response was developed. Each marker test was defined as positive (predictive of non-response) if the value of that tumor marker increased at least 50% from the value at baseline and above a marker dependent minimum value to be determined. Also, tests based on combination of multiple markers were designed. Specificity and sensitivity for predicting non-response was calculated and results were validated in an independent cohort. The target specificity of the test for detecting non-response was set at >  95%, in order to allow its safe use for treatment decisions.
RESULTS: A total of 376 patients (training cohort: 180, validation cohort: 196) were included in our analysis. Results for the specificity of the single marker tests in the validation set were CEA: 98·3% (95% CI: 90·9-100%), NSE: 96·5% (95% CI: 87·9-99·6%), SCC: 96·5% (95% CI: 88·1-99·6%), Cyfra21·1 : 91.8% (95% CI: 81·9-97·3%), and CA125 : 86·0% (95% CI: 74·2-93·7%). A test based on the combination of Cyfra21.1, CEA and NSE accurately predicted non-response in 32.3% (95% CI 22.6-43.1%) of patients 6 weeks after start of immunotherapy. Survival analysis showed a significant difference between predicted responders (Median PFS: 237 days (95% CI 184-289 days)) and non-responders (Median PFS: 58 days (95% CI 46-70 days)) (p <  0.001).
CONCLUSIONS: Serum tumor marker based tests can be used for accurate detection of non-response in NSCLC, thereby allowing early and safe discontinuation of immunotherapy in a significant subset of patients.

UNASSIGNED: To assess the association between common-used serum tumor markers and recurrence of lung adenocarcinoma and squamous cell carcinoma separately and determine the prognostic value of serum tumor markers in lung adenocarcinoma featured as ground glass opacities.
UNASSIGNED: A total of 2,654 non-small cell lung cancer patients undergoing surgical resection between January 2008 and September 2014 were analyzed. The serum levels of carcinoma embryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were tested preoperatively. Survival analyses were performed with COX proportional hazard regression.
UNASSIGNED: Among patients with lung adenocarcinoma, elevated preoperative serum CEA(HR=1.246, 95%CI:1.043-1.488, P=0.015), CYFRA21-1(HR=1.209, 95%CI:1.015-1.441, P=0.034) and CA125(HR=1.361, 95%CI:1.053-1.757, P=0.018) were significantly associated with poorer recurrence free survival (RFS). Elevated preoperative serum CA199 predicted worse RFS in patients diagnosed with lung squamous cell carcinoma (HR=1.833, 95%CI: 1.216-2.762, P=0.004). Preoperative serum CYFRA21-1(HR=1.256, 95%CI:1.044-1.512, P=0.016) and CA125(HR=1.373, 95%CI: 1.050-1.795, P=0.020) were independent prognostic factors for patients with adenocarcinoma presenting as solid nodules while serum CEA (HR=2.160,95%CI:1.311-3.558, P=0.003) and CA125(HR=2.475,95%CI:1.163-5.266, P=0.019) were independent prognostic factors for patients with adenocarcinoma featured as ground glass opacities.
UNASSIGNED: The prognostic significances of preoperative serum tumor markers in non-small cell lung cancer were associated with radiological features and histological types.

UNASSIGNED: Surgically resected stage I lung adenocarcinoma (ADC) has wide variation in prognosis. It is significant to identify high-risk patients and optimize therapeutic strategy. This study aimed to investigate the relationships among histological grade, serum tumor marker index (TMI), morphological computer tomography (CT) features, and a well-established prognosticator cell proliferation (Ki-67) in stage I ADC.
UNASSIGNED: Preoperative CT was performed in 182 patients with stage I ADC confirmed by pathology. The Ki-67 expression was acquired by immunohistochemistry. TMI was the square root of standardized serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) values. Tumor shadow disappearance rate (TDR) and other morphological CT features were interpreted by two radiologists. Histological grade, TMI, CT features were statistically evaluated to explore the associations with Ki-67 expression.
UNASSIGNED: In univariate analysis, gender, smoking history, pack-year, histological grade, TNM stage (IA and IB), serum CEA and CYFRA 21-1 status, TMI status, as well as TDR, long-axis diameter, short-axis diameter, lobulation, spiculation, attenuation types, vacuolation, vascular invasion, vascular convergence, thickened bronchovascular bundles, pleural attachment and peripheral fibrosis were significantly associated with Ki-67 expression (all P<0.05). Solid-predominant ADC had the highest Ki-67 expression, followed by micropapillary, papillary and acinar-predominant ADC, while lepidic-predominant ADC had the lowest Ki-67 expression (P<0.001). TDR was negatively correlated with Ki-67 (r =-0.478, P<0.001). Multivariate logistic regression analysis revealed that gender, histological grade, TDR and attenuation types were independent factors associated with Ki-67 expression.
UNASSIGNED: Ki-67 expression differed distinctly according to ADC histological subtypes. High Ki-67 expression is independently associated with male patients of stage I ADC with worse differentiation, lower TDR and solid tumors, which might be of prognostic value for poor prognosis in stage I ADC.

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC.
METHODS: Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared.
RESULTS: A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II-IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125.
CONCLUSIONS: High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.