Correlation of circulating tumor DNA EGFR mutation levels with clinical outcomes in patients with advanced lung adenocarcinoma.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS: Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

Solitary metastasis to the skin and colon from gastric cancer after curative gastrectomy and chemotherapy: A case report.

RATIONALE: Gastric cancer usually spread via blood circulation to liver, lung, bone, and kidney after recurrence, but it is extremely rare in clinical practice that gastric carcinoma metastasizes to the skin and colon without metastasis to common sites like liver or lung. PATIENT CONCERNS: A 57-year-old man was admitted to the hospital with altered bowel habit and hematochezia for 2 weeks. DIAGNOSES: The patient was diagnosed with advanced gastric cancer at stage IIIA (pT3N2M0) two and a half years ago. Cutaneous metastasis from gastric cancer was confirmed by cutaneous biopsy 2 years following curative gastrectomy. Unfortunately, colonic metastasis from gastric cancer was found by PET-CT 6 months after the diagnosis of cutaneous metastasis. INTERVENTIONS: The patient was given chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for the skin metastasis. Right hemicolectomy was performed when the malignant tumor of the colon was found, in order to relieve the symptom, and improve the quality of life. OUTCOMES: The patient was treated with chemoradiotherapy in a local hospital, the peritoneal carcinomatosis occurred 5 months after the second operation, and died 9 months after the diagnosis of colonic metastasis. LESSONS: Our case represents a rare condition that solitary cutaneous and colonic metastasis from gastric cancer can occur after surgical resection and systemic chemotherapy. Its unique clinicopathological features can extend our insights on gastric cancer, and it may provide clinicians with some positive clinical experience for identifying and treating this disease.

Location of the supraorbital and infraorbital foramen with references to the soft tissue landmarks in a Chinese population.

The purpose of the current study was to determine the supraorbital foramen (SOF) and infraorbital foramen (IOF) based on soft tissue landmarks, to facilitate prediction of the location of this structure during facial surgery. Forty-two hemispheres of 21 adult cadavers (16 men and 5 women; aged 30-75 years) were dissected to expose the SOF and IOF. The locations of the SOF and IOF were evaluated with direct and photographic measurements. The data gained were analyzed by statistical method. The SOF localized 23.11 ± 2.35 mm superior and 9.48 ± 3.06 mm lateral to the angulus oculi medialis (AOM). The vertical angle from AOM to SOF was 68.3 (SD, 6.44) degrees. The SOF localized 24.81 (SD, 3.39) mm inferior and 10.89 (SD, 2.78) mm lateral to the AOM on the front view. The vertical angle from AOM to IOF was 66.5 (SD, 5.18) degrees. The SOF localized 11.22 (SD, 2.01) mm inferior and 6.09 (SD, 2.32) mm lateral to the ala of the nose (AL) on the front view. The vertical angle from AL to IOF was 61.7 (SD, 7.61) degrees. These results were a little different from the results of some other populations. We found the IOFs located on the point of one-fifth proportion distant to the ALs along the vertical direction distance from AL to SOF, whereas the AOMs located on the point of three-fifths proportion distant from the AL. Our results may provide more detailed information to predict the location of the SOFs and IOFs and help to prevent nerve or vessel damage.