Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

The aim of this study was to investigate the associations between secondary mutations of c-KIT/PDGFRα and acquired imatinib resistance or efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors (GISTs). Mutations of c-KIT (exons 9, 11, 13, 14, 17, and 18) and PDGFRα (exons 12 and 18) in tumor samples of 50 patients were analyzed by direct sequencing. A total of 50 samples before imatinib and 52 samples after imatinib were collected. Among 52 samples after imatinib, 38 samples were imatinib resistant and 14 samples were imatinib sensitive. All patients before imatinib treatment had primary mutations of c-KIT exon 11 (n = 45) or exon 9 (n = 5), and no PDGFRα mutations were found in these patients. After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. In our study, 19 patients received sunitinib treatment after the failure of imatinib, and it seemed that the median progression-free survival (7 vs. 19 months, P = 0.244) in patients with secondary mutations (n = 13) was lower than that in patients without secondary mutations (n = 6). Secondary mutations of c-KIT were significantly associated with acquired resistance to imatinib in Chinese GIST patients, and whether secondary mutations of c-KIT could influence the efficacy of sunitinib needed to be further investigated.

To investigate the correlation between C-KIT/PDGFRα mutations and Imatinib response or survival in Chinese advanced gastrointestinal stromal tumor (GIST) patients. Clinical data and paraffin-embedded tumor specimens were collected from 158 advanced GIST patients receiving first-line Imatinib. Mutation analyses of C-KIT gene (Exons 9, 11, 13, and 17) and PDGFRα gene (exons 12 and 18) were performed by PCR amplification and Sanger sequencing. A total of 135 patients harboring C-KIT mutations (exon 11 mutation: 108; exon 9 mutation: 23; exon 13 mutation: 2; exon 17 mutation: 2) and one patients carrying PDGFRα mutation (exon 18) were found in this study. Twenty-two patients (13.9 %) with neither C-KIT nor PDGFRα mutations were named as wild type. The response rate (64.7 vs. 36.4 %, P = 0.000) and median progression-free survival (28 vs. 8 months, P = 0.000) of mutant patients (n = 136) were significantly higher than those of wild-type patients (n = 22). Moreover, the response rate and median progression-free survival in patients with exon 11 mutations (n = 108), exon 9 mutations (n = 23), and wild-type patients (n = 22) were 68.5, 47.8, and 36.4 % (P = 0.001), and 31 months, 13 months, and 8 months (P = 0.000), respectively. No significant differences of response rate or median progression-free survival were seen in patients with exon 11 deletion mutations, point mutations, and mixed-type mutations. C-KIT mutations were closely associated with Imatinib response and progression-free survival of Chinese advanced GIST patients. Other predictive markers for Imatinib would be further investigated.

Background Radiotherapy is a highly effective treatment for cervical cancer. Recent studies focused on the radiotherapy induced anti-tumor immunity. Whether tumor-derived extracellular vesicles (EVs) play roles in radiotherapy induced tumor associated macrophage (TAM) polarization remains unclear. Materials and Methods This study analysed the phenotype of macrophages in cancer tissue and peripheral blood of cervical cancer patients using flow cytometry analysis. The role of EVs from plasma of post-irradiated patients on M2-like transformed macrophages was assessed. The M1- and M2-like macrophages were assessed by expression of cell surface markers (CCR7, CD163) and intracellular cytokines (IL-10, TNFα and iNOS). The capacity of phagocytosis was assessed by PD-1 expression and phagocytosis of pHrodo Red E. coli bioparticles. Results Our results demonstrated that radiotherapy of cervical cancer induced an increase in the number of TAMs and a change in their subtype from the M2-like to the M1-like phenotype (increased expression of CCR7 and decreased expression of CD163). The EVs from plasma of post-irradiated patients facilitated the M2-like to the M1-like phenotype transition (increased expression of CCR7, TNFα and iNOS, and decreased expression of CD163 and IL-10) and increased capacity of phagocytosis (decreased PD-1 expression and increased phagocytosis of pHrodo Red E. coli bioparticles). Conclusions Our data demonstrated that irradiation in cervical cancer patients facilitated a proinflammatory macrophage phenotype which could eventually able to mediate anti-tumor immune responses. Our findings highlight the importance of EV in the crosstalk of tumor cells and TAM upon irradiation, which potentially leading to an increased inflammatory response to cancer lesions.