CEA dynamics for predicting response after anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer.

Carcinoembryonic antigen (CEA) is the most widely used tumor marker in metastatic colorectal cancer (mCRC). However, its potential as a predictive marker of progression in mCRC during systemic chemotherapy, particularly in patients receiving monoclonal antibodies as a combination therapy, has remained of interest. Herein, we investigated whether CEA changes could predict disease progression and clinical outcomes in patients with mCRC cotreated with systemic chemotherapy and/or biologic agents. A total of 1261 patients with mCRC undergoing a first-line systemic treatment were included in this retrospective study. We analyzed the optimal cut-off value for CEA changes to predict progression at the first response evaluation by the treatment arm (chemotherapy alone, chemotherapy plus anti-vascular endothelial growth factor (VEGF) monoclonal antibody [mAb], and chemotherapy plus anti-epidermal growth factor receptor [EGFR] mAb). These cut-off values were then used to predict overall survival (OS) and progression-free survival (PFS). When stratified by their treatment arm, 891 (70.6%), 266 (21.0%), and 104 (8.2%) of the study patients were included in the chemotherapy alone-, anti-VEGF mAb, and anti-EGFR mAb groups, respectively. The optimal CEA cut-off values were 16.5% and 38.9% increase in the whole cohort and anti-EGFR mAb group, respectively, and these values showed high sensitivity and specificity for predicting disease progression. The patients in the entire population and anti-EGFR mAb group with CEA changes below these cut-off values showed significantly better OS and PFS outcomes compared those whose changes were above cut-off values. Among the patients with mCRC treated with anti-VEGF mAb, no associations were found between OS or PFS outcomes and CEA changes. CEA is potentially a good surrogate marker for predicting disease progression and survival outcomes in patients with mCRC receiving first-line systemic chemotherapy alone or chemotherapy with anti-EGFR mAb, whereas it is less effective in those treated with anti-VEGF mAb.

Increased incidence of chemoport-related thrombosis in patients with colorectal cancer receiving bevacizumab: A single-institutional experience.

OBJECTIVE: Chemoport-related thrombosis (CRT) is a serious complication that causes morbidities and interrupts administration of intravenous cancer therapy. We investigated the incidence and risk of CRT in colorectal cancer (CRC) patients treated with bevacizumab (BEV). METHODS: We retrospectively reviewed 1,534 CRC patients who received chemotherapy with or without BEV using a chemoport between 2014 and 2016. RESULTS: The participants had a median age of 58 (18-85) years, and 60.3% were male. All participants were stratified into three groups: adjuvant chemotherapy (AC) (n=670), palliative chemotherapy (PC) without BEV (n=356), and PC with BEV (n=508). The median follow-up was 20.19 (interquartile range, 14.07-27.19) months. CRT occurred in 3.8% of all patients; incidence of symptomatic and asymptomatic CRT was 2.9% and 0.9%, respectively. CRT occurred more in patients with BEV (5.7%) than in patients without BEV (2.9%, P=0.008). The cumulative incidence of CRT in patients administered PC with BEV was significantly higher than that in those administered AC (P=0.011) and there was a trend toward increased CRT in patients administered PC with BEV compared with those administered PC without BEV (P=0.044). Multivariate analysis found that BEV treatment was the only variable that was significantly associated with CRT (hazard ratio, 2.06; 95% confidence interval, 1.24-3.43; P=0.006). CONCLUSIONS: BEV treatment was significantly associated with increased incidence of CRT in CRC patients.

Process Innovation Improves Trial Operation Efficiency.

BACKGROUND: Despite the fact that unaddressed delays in clinical trial operation could severely compromise the overall effort invested, there seems to be a lack of concerted effort in reforming such delays. This study evaluated the composite effect of initiatives in reforming trial operation efficiency. METHODS: A high-volume academic medical center in Korea has implemented various initiatives to improve the trial operation efficiency by expediting times from institutional review board (IRB) submission to approval, from IRB submission to trial open for subject enrollment, and from trial open to first patient-in. The initiatives include implementation of the protocol preliminary review, parallel processing of the clinical trial agreement review in line with the protocol submission to the IRB, and involvement of project manager for operational risk management. Times from IRB submission to approval, from IRB submission to trial open, and from trial open to first patient-in before and after implementation of initiatives were compared. RESULTS: The median time required in IRB approval was meaningfully shorter in the postinitiative group (19 vs 14 days; P < .001). The median times from IRB submission to trial open for subject enrollment and from trial open to first patient-in were reduced significantly in the postinitiative group (trial open: 25 vs 18 days, P < .001; first patient-in: 111.5 vs 100 days, P = .014). CONCLUSIONS: The initiatives were effective in reforming trial operational efficiency. Additional studies to address the cause of operational delay and modifiable factors influencing subject enrollment are needed to further improve operational efficiency.