The Effects of Drug Exposure and Single Nucleotide Polymorphisms on Aaptinib-Induced Severe Toxicities in Solid Tumors.

To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

[Clinical and imaging diagnosis of primary hepatic lymphoma].

OBJECTIVE: To investigate the clinical and imaging features of primary hepatic lymphoma (PHL). METHODS: Four PHL cases were analyzed retrospectively for clinical manifestations, transcatheter hepatic arterial angiography and CT features. RESULTS: All the four cases were B-cell non-Hodgkin lymphoma proven by histological and immunohistochemical examination. The main clinical manifestations included pain in the right upper quadrant and B symptoms of the lymphoma (fever, night sweating, and weight loss) in 3 patients. Three cases were complicated by chronic hepatitis or cirrhosis, and the other had renal transplantation two years ago. All these cases exhibited elevated serum lactate dehydrogenase (LDH) level, which was reduced after surgery or chemotherapy. Plain CT scan all identified hypodense lesions which did not display marked enhancement on the arterial phase and portal venous phase scans. On delayed phase scan, the border of the lesions became clear, and slight enhancement was observed in the peripheral and some partitions of the lesions. Angiographic imaging displayed slight tumor staining and arterial displacement in the liver in all the cases with thin tumor-supplying vessels. Global staining or abnormally thickened vessels were not seen. CONCLUSION: A comprehensive evaluation of the clinical manifestations and imaging features can be helpful in the diagnosis of PHL, and serum LDH level may help to assess the therapeutic effect.

[18F-FDG positron emission tomography for mediastinal staging of lung cancer].

OBJECTIVE: To evaluate the diagnostic value of (18)F-FDG positron emission tomography (PET) in mediastinal staging of lung cancer. METHOD: A retrospective analysis of mediastinal staging was carried out in 41 cases of lung cancer by comparing the preoperative mediastinal FDG PET and CT findings with the pathological results. RESULTS: According to the pathological results, 18 patients had mediastinal metastasis, 17 of whom were correctly identified by FDG PET, and 10 by CT. Of the other 23 patients without mediastinal metastasis pathologically, 22 were correctly diagnosed by FDG PET and 20 by CT. The sensitivity and accuracy for diagnosis of regional mediastinal lymph node metastasis with FDG PET were 94.4% and 95.1%, obviously higher than those of CT (55.6% and 73.2%, P<0.05). CONCLUSION: FDG PET is a better alternative for mediastinal staging of lung cancer, specially for identification of small lymph node metastasis escaping detection by CT, to provide important evidence for clinical staging and treatment planning of lung cancer.

[18F-Fluorodeoxyglucose uptake in hepatocellular carcinoma on positron emission tomography correlates with alpha-fetoprotein].

OBJECTIVE: To investigate whether (18)F-fluorodexyglucose (FDG) uptake in the primary hepatocellular carcinoma (HCC) correlates with serum alpha-fetoprotein (AFP). METHODS: Forty-five patients with histologically confirmed HCC underwent whole-body (18)F-FDG PET examination. Standardized uptake value (SUV) and tumor-to-nontumor ratio of the SUV (SUVratio) were calculated, and the relationship between serum AFP and glucose metabolism in HCC was analyzed. RESULTS: Of the 45 cases, the primary tumor and metastatic lymph nodes were clearly displayed on PET images in 43 cases and the well-differentiated tumors were shown negative in the other 2 cases. A linear correlation of the AFP with SUV (r=0.426, P<0.05) and SUVratio (r=0.532, P<0.001) was noted. CONCLUSION: Serum AFP correlates significantly with both SUV and SUN ratio, indicating that AFP is involved in glucose metabolism and cell proliferation in HCC.

Clinical application of transarterial embolization for massive hemorrhage in the nasopharyngeal and maxillofacial regions.

OBJECTIVE: To study the effect and safety of transarterial embolization (TAE) in the management of massive hemorrhage in the nasopharyngeal and maxillofacial regions. METHODS: Forty-two cases of massive hemorrhage in the nasopharyngeal and maxillofacial regions were treated by TAE. Gelfoam particles, polyvinyl acohol particles, and metallic coil were used to for embolism of the external carotid artery, maxillary artery, facial artery, occipital artery, sphenopalatine artery and ascending pharyngeal artery respectively according to the angiographic findings and the region of hemorrhage sites. RESULTS: TAE was successfully performed in all the cases, and no recurrence or serious complications were observed in the 3 to 12-month follow-up. CONCLUSION: TAE is safe and effective in the treatment of massive hemorrhage in the nasopharyngeal and maxillofacial regions.