Unusual increase in carcinoembryonic antigen despite response to selpercatinib in two patients with medullary thyroid cancer

Introduction: Serum calcitonin (CT) and carcinoembryonic antigen (CEA) are valuable tumour markers in patients with medullary thyroid carcinoma (MTC). Both markers most often evolve in parallel after treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant MTC patients. Case presentation: We report two observations of RET-mutant progressive metastatic and symptomatic MTC patients who were treated with selpercatinib. Patient 1, a 61-year-old man, presented dyspnoea and diarrhoea at selpercatinib initiation with large neck lymph nodes and lung metastases. Patient 2, a 76-year-old man, had acute discomfort with flush and diarrhoea, with small but diffuse bone and liver disease. Both patients had an objective response with rapid clinical improvement and RECIST 1.1 response (-90%) in patient 1. A rapid dramatic decrease in CT level was observed in both patients (-99% in both patients) while CEA levels gradually and sustainably increased after selpercatinib initiation (+207% at cycle 15 in patient 1 and + 835% at cycle 14 in patient 2). In both patients, FDG PET/CT did not show any abnormal uptake that could explain the CEA increase. Colonoscopy and oesogastric fibroscopy showed colonic polyposis with mild oesophagitis and gastritis in patient 1 and were normal in patient 2. Conclusion: These observations show an unusual and lasting increase in serum CEA in two MTC patients who exhibited an objective tumour response to selpercatinib. The mechanism behind this unexpected rise in CEA level remains unknown. The frequency of this evolving profile will be determined in further phase III studies.

A Potential Serum Biomarker for Screening Lung Cancer Risk in High Level Environmental Radon Areas: A Pilot Study

Radon is a major cause of lung cancer (LC) deaths among non-smokers worldwide. However, no serum biomarker for screening of LC risk in high residential radon (HRR) areas is available. Therefore, the aim of this study was to determine diagnostic values of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), human epididymis protein 4 (HE4), interleukin 8 (IL-8), migration inhibitory factor (MIF), tumor nuclear factor-alpha (TNF-α) and vascular endothelial growth factors (VEGF) occurring in high radon areas. Seventy-five LC non-smoker patients and seventy-five healthy controls (HC) were enrolled in this study. Among the HC groups, twenty-five HC were low residential radon (LRR) and fifty HC were HRR. Significantly higher (p < 0.0004) serum levels of CEA, Cyfra21-1, IL-8 and VEGF were found in the LC compared with the LRR and HRR groups. More importantly, significantly higher levels (p < 0.009) of serum CEA, Cyfra21-1 and IL-8 were observed in HRR compared with the LRR group. Likewise, a ROC curve demonstrated that serum CEA and Cyfra21-1 could better distinguish LC risk from HRR groups than IL-8. These results indicated that serum CEA and Cyfra21-1 were significantly increased in the HRR group and may be considered as potential biomarkers for individuals at high-risk to develop LC.

Clinicopathologic features and prognostic value of DNA mismatch protein expression patterns in stage Ⅱ/Ⅲ colorectal cancer.

Background MSI CRCs were associated with better prognosis and limited predictive value for adjuvant chemotherapy. However, whether the same is true in Northeastern China is still unclear. The aim of the present study was to evaluate the association of clinicopathologic features and MMR/MSI status determined with immunohistochemistry analysis in Northeast China patients with stage Ⅱ/Ⅲ CRCs. Particularly, we sought to detect the relationship between MMR/MSI status and efficacy of oxaliplatin and fluoropyrimidine based adjuvant chemotherapy. Methods In total, 476 pathological specimens from eligible stage Ⅱ/Ⅲ CRCs were analyzed with IHC between 2016 and 2018, of which 63 CRCs were diagnosed with MMR protein deficiency. Clinicopathological features and overall survival (OS) were compared between these above two groups. Result The incidence of dMMR CRCs in our cohort was 13.2% (63/476). Immunohistochemistry (IHC) revealed two common dMMR IHC patterns in 63 dMMR CRCs. And dMMR type1 showed a higher proportion of women (P=0.001) and earlier pathological N stage (P=0.075). In the multivariate Cox regression model, POC (Postoperative chemotherapy) and dMMR were associated with a favor prognosis in CRC patients with stage II/III (HR 0.47, 95%CI 0.30-0.74, P=.001; HR 0.34, 95%CI 0.14-0.79, P=.013). However, adjuvant chemotherapy based on oxaliplatin and fluorouracil cannot prolong the OS of dMMR CRCs (P=0.182). Conclusions MMR protein appeared distinct associations with tumor staging, serum CEA level and tumor size. And MMR protein was an independent prognostic marker in patients with stage Ⅱ CRC, whereas dMMR CRC patients did not seem to benefit from oxaliplatin combined with fluorouracil-based adjuvant chemotherapy.

Clinicopathologic Features and Prognostic Value of DNA Mismatch Repair Statues for Stage Ⅱ/Ⅲ Colorectal Cancer in Northeast China.

Background MSI CRCs were associated with better prognosis and limited predictive value for adjuvant chemotherapy. However, whether the same is true in Northeastern China is still unclear. The aim of the present study was to evaluate the association of clinicopathologic features and MMR/MSI status determined with immunohistochemistry analysis in Northeast China patients with stage Ⅱ/Ⅲ CRCs. Particularly, we sought to detect the relationship between MMR/MSI status and efficacy of oxaliplatin and fluoropyrimidine based adjuvant chemotherapy.MethodsIn total, 476 pathological specimens from eligible stage Ⅱ/Ⅲ CRCs were analyzed with IHC between 2016 and 2018, of which 63 CRCs were diagnosed with MMR protein deficiency. Clinicopathological features and overall survival (OS) were compared between these above two groups. Result The incidence of dMMR CRCs in our cohort was 13.2 % (63/476). Immunohistochemistry (IHC) revealed two common dMMR IHC patterns in 63 dMMR CRCs. And dMMR type1 showed a higher proportion of women (P=0.001) and earlier pathological N stage (P=0.075). In the multivariate Cox regression model, POC and dMMR were associated with a favor prognosis in CRC patients with stage II/III (HR 0.47, 95%CI 0.30-0.74, P=.001; HR 0.34, 95%CI 0.14-0.79, P=.013). However, adjuvant chemotherapy based on oxaliplatin and fluorouracil cannot prolong the OS of dMMR CRCs (P=0.182). Conclusions MMR protein appeared distinct associations with tumor staging, serum CEA level and tumor size. And MMR protein was an independent prognostic marker in patients with stage Ⅱ CRC, whereas dMMR CRC patients did not seem to benefit from oxaliplatin combined with fluorouracil-based adjuvant chemotherapy.

Efficacy Evaluation and Prognosis Analysis of CT-Guided Radiofrequency Ablation for Non-Small Cell Lung Cancer

Background: Lung cancer has a high morbidity and mortality, and has the highest incidence of all malignancies in men in China. In recent years, radiofrequency ablation (RFA) has become the fourth promising treatment for lung cancer.Method: We followed up patients with non-small cell lung cancer in the First Affiliated Hospital of Anhui Medical University to investigate the survival, complications and prognosis of RFA.Results: Among 34 patients, there were 25 men and nine women (age range 22–84 years; 64% aged 60–80 years. The mean diameter of lung lesions was 2.46±0.89 cm. The pathological types were adenocarcinoma (27/34, 79.41%) and squamous cell carcinoma (7/34, 20.59%). Half of the patients had reached stage IV at the time of the study. Sixteen patients had elevated carcinoembryonic antigen (CEA). Six patients did not receive any further treatment after RFA and nine received chemotherapy combined with targeted therapy. The median follow-up period was 18 (7.0–33.5) months. Complications of RFA were reported in 15 patients (44.12%) and the most common were pneumothorax and pleural effusion. The risk of complications was higher in smokers than in non-smokers (P<0.05). The median overall survival was 22 (2.58–41.42) months, and the overall survival rate was 69.78% (1 year), 59.10% (18 months) and 48.85% (2 years). The survival rate of patients with lung lesions diameter ≤2 cm was significantly higher than that of patients with lesion diameter >2 cm (P<0.05). The annual survival rate of patients with elevated serum CEA before RFA was significantly lower than that of patients with normal serum CEA (P<0.05). Patients with chemotherapy combined with tyrosine kinase inhibitors (TKIs) had significantly higher survival rates compared with patients with only chemotherapy or TKI/no treatment (P<0.05). Conclusion: CT-guided RFA is a safe and effective treatment for lung cancer. Small lesions and combined therapy can result in longer survival. Patients with serum increased CEA have poor survival.

Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p &lt; 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p &lt; 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p &lt; 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p &lt; 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p &lt; 0.001).Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.

Risk factors for lymph node metastasis and surgical scope in patients with cN0 non-small cell lung cancer: a single-center study in China

Background It is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC. Methods We conducted a retrospective study of patients with tumor size ≤ 30 mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors. Results Overall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5 mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI 0.780–0.870); the cut-off value of serum CEA level was 1.765 μg/L, and the AUC was 0.661 (p < 0.001, 95% CI: 0.568–0.754). Moreover, 8 of 461 patients with tumor parenchyma ≤ 16.5 mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5 mm had lymph node metastasis. Conclusion Tumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size ≤ 30 mm. For patients with tumor parenchyma > 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. For patients with tumor parenchyma ≤ 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible.

Association Between Serum Carcinoembryonic Antigen Levels at Different Perioperative Time Points and Colorectal Cancer Outcomes

BackgroundWhether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial.Patients and MethodsPrimary and sensitivity analysis populations were obtained from a retrospective, multicenter longitudinal cohort including consecutive patients without neoadjuvant treatment undergoing curative resection for stage I–III CRC. Serum CEA levels before (CEApre-m1) and within 1 (CEApost-m1), 2–3 (CEApost-m2–3), and 4–6 months (CEApost-m4–6) after surgery were obtained, and their associations with recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox regression. Sensitivity and subgroup analyses were performed.ResultsPrimary and sensitivity analysis populations included 710 [415 men; age, 54.8 (11.6) years] and 1556 patients [941 men; age, 56.2 (11.8) years], respectively. Recurrence hazard ratios (HRs) in the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups were 1.30 (95% CI: 0.91–1.85), 1.53 (95% CI: 0.89–2.62), 1.88 (95% CI: 1.08–3.28), and 1.15 (95% CI: 0.91–1.85), respectively. The HRs of the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups for OS were 1.09 (95% CI: 0.60–1.97), 2.78 (95% CI: 1.34–5.79), 2.81 (95% CI: 1.25–6.30), and 3.30 (95% CI: 1.67–.536), respectively. Adjusted multivariate analyses showed that both in the primary and sensitivity analysis populations, elevated CEApost-m2–3, rather than CEApre-m1, CEApost-m1, and CEApost-m4–6, was an independent risk factor for recurrence, but not for OS. The RFS in the elevated and normal CEApost-m2–3 groups differed significantly among patients with stage II disease [n = 266; HR, 2.89; 95% CI, 1.02–8.24 (primary analysis); n = 612; HR, 2.69; 95% CI, 1.34–5.38 (sensitivity analysis)].ConclusionsElevated postoperative CEA levels are prognostic in patients with stage II CRC, with 2–3 months after surgery being the optimal timing for CEA measurement.

Clinical Effects of Chinese Herbal Decoction Combined with Basic Chemoradiotherapy and Nursing Intervention in the Treatment of Cervical Cancer and the Effect on Serum CEA, CA125, and TNF-α Levels

Objective. This study was aimed to investigate the clinical effect of Chinese herbal decoction combined with basic chemoradiotherapy and nursing intervention in the treatment of cervical cancer and the effect on serum carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and tumor necrosis factor-α (TNF-α) levels. Methods. A total of 200 cervical cancer patients in our hospital from June 2015 to November 2018 were selected and randomly divided into a study group and a control group. The control group was given chemoradiotherapy and psychological nursing treatment, and the study group was given self-made Chinese herbal decoction on the basis of the control group. The clinical efficacy and serum CEA, CA125, and TNF-α levels were assessed. Results. After treatment, the total effective rate of the study group was significantly higher than that of the control group. The levels of serum CEA, CA125, and TNF-α were decreased in the two groups after treatment, and the decrease in the study group was more significant than that in the control group. After treatment, CD3+ and CD4+ levels were increased compared with those before treatment, and the increase in the study group was also more obvious than that of the control group. The level of CD8+ was decreased compared with before treatment, and the decrease in the study group was more notable than that of the control group. The two-year cumulative survival rate of the study group was markedly higher than that of the control group. The quality-of-life of patients treated for 3 months, 1 year, and 2 years was dramatically improved compared to before treatment. The incidence of adverse reactions in the study group was lower than that of the control group. Conclusion. The treatment of basic chemoradiotherapy and psychological nursing intervention combined with Chinese herbal decoction on cervical cancer patients can improve the clinical treatment effects, improve the patient’s body immunity, reduce serum CEA, CA125, and TNF-α levels, prolong survival time, improve life quality, and reduce the incidence of adverse reactions, and it is worthy of clinical promotion.