Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma.

BACKGROUND: We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. METHODS: Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. RESULTS: We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). CONCLUSIONS: Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Assessment of the cardiac safety between cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory mCRC.

OBJECTIVE: The cardiac safety of cetuximab and panitumumab, particularly as single agents, has not been investigated extensively. This trial was designed to specifically evaluate the cardiac safety of cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Sixty-one patients received cetuximab at an initial dose of 400 mg/m2 intravenously over 120 minutes on day 1 (week 1), followed by a maintenance dose of 250 mg/m2 intravenously over 60 minutes on day 1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6 mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram (ECG) were performed at baseline, during therapy and after the treatment (4th and 10th months). The incidence of elevation of troponin I ultra (TNI Ultra), abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded and analyzed. RESULTS: The incidence of elevation of TNI Ultra between the two groups had no significance (p=0.681), and TNI Ultra+ was observed more frequently in patients with metastases to more than three organs and they received fourth or above lines of chemotherapy. The most frequent abnormal ECG manifestations were nonspecific ST changes and QTc prolongation in the two groups. At 10 months after treatment, most of the abnormal ECG manifestations were reversed. The most common cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest pain and arrhythmias requiring treatment. Most of the events were mild and transient. The incidence of cardiac AEs had no significant difference between the two groups. Rash was still the most common noncardiac AE in both groups. CONCLUSION: Cetuximab and panitumumab showed favorable cardiac safety as single agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for cardiac AEs is still necessary throughout the entire treatment process.

The cardiotoxicity of cetuximab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer patients.

The cardiac safety of cetuximab, particularly as single approach, has not been investigated extensively. This trial was designed to evaluate the cardiac safety of cetuximab as salvage monotherapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients.Cetuximab was administrated at an initial dose of 400 mg/mon day 1 (week 1), followed by a maintenance dose of 250 mg/m on day 1 of each 7-day cycle. Electrocardiograph (ECG), routine laboratory tests, and troponin I (TNI) Ultra were performed at baseline, during, and after the cetuximab therapy. The incidence of abnormal ECGs, elevated TNI Ultra, cardiac events, and noncardiac events were recorded and analyzed.TNI Ultra+ was found in 20 patients (32.3%) during the cetuximab therapy.TNI Ultra+ occurred more frequently in patients with more than 3 organs affected and accepted fourth or above lines of chemotherapy. The most frequent abnormal ECG was ST depression in 24 (38.7%) patients. The elevated TNI Ultra and abnormal ECGs could recover after the cetuximab therapy. The most of cardiac adverse events were mild and transient and the noncardiac adverse events were also consistent with the known safety profile for cetuximab.Cetuximab showed its cardiac safety as a single agent for chemotherapy-refractory mCRC patients. And TNI Ultra and ECG could be sensitive and convenient approaches for the surveillance of adverse events.