Objective To investigate postoperative recurrent pattern of the thoracic esophageal squamous cell carcinoma (TESCC),aiming to provide a basis for the delineation of postoperative radiotherapy volume for TESCC.Methods Clinical data of 66 TESCC patients who recurred after the radical esophagectomy in Zhongnan Hospital of Wuhan University from 2011 to 2017 were retrospectively analyzed.According to the AJCC 8th edition-defined classification of esophageal carcinoma,regional lymph node stations Ⅰ to 8M were defined as the upper-middle mediastinum region (UMMR),and stations 8Lo,9 and 15 were defined as the inferior mediastinum region (IMR),stations 16 to 20 were regarded as the upper abdominal lymph node region (UAR).Results Among all 66 patients,41 cases (62%) experienced locoregional recurrence alone,25 cases (38%) presented with distant metastasis alone.A total of 54 patients with 148 lymph node recurred after treatment.The highest risk region of lymph node recurrence was UMMR (118/148,80%),after that,followed by UAR (24/148,17%).With regard to 9 cases of UAR,6 patients had lower TESCC,and 8 patients (89%) were graded as ≥ pathological stage Ⅲ.Conclusions The highest risk region of lymph node recurrence is UMMR in TESCC patients undergoing radical esophagectomy,which should be considered as the target volume in postoperative radiotherapy.For patients with lower TESCC ≥ pathological stage Ⅲ,UAR might be the target volume with cautions.Anastomosis and IMR are probably not the routine treatment volumes.
Background The clinical target volume (CTV) for postoperative radiotherapy for thoracic esophageal squamous cell carcinoma (TESCC) needs to be defined. The study aim was to map metastatic lymph nodes (LNMs) in a computed tomography (CT)-based atlas and delineate the postoperative radiotherapy target area. Methods Sixty-nine TESCC patients with first recurrent regional LNMs after esophagectomy were included. The LNM epicenters were registered onto corresponding anatomic axial CT images of a standard patient in the treatment position, with reference to the surrounding vascular and bony structures. The LNM sites were based on lymph node map of esophageal cancer, AJCC 8th. The lymph metastasis risk for different segments of thoracic esophagus was assessed. Results One hundred and seventy-nine LNMs were mapped onto standard axial CT images. The upper-middle mediastinum region (station 1 to 8 M) contained 97% of metastases in the upper segment of thoracic esophagus, 90% in the middle segment, and 66% in the lower one. Advanced pathological stage (≥IIIB) might be a predictive factor for upper abdominal region (UAR) relapse in lower TESCC. Lower cervical para-tracheal LNMs were within a 4.3-cm bilaterally expanded area from the midline of the body and a 2.2-cm expanded area from the anterior of vertebral body, from the superior border of the C7, to the inferior border of the first thoracic vertebra. Conclusion A modified target from the upper border of C7 to the lower border of caudal margin of the inferior pulmonary vein level could cover the high-risk area of TESCC underwent postoperative radiotherapy. UAR seems to be an elective irradiation target for lower TESCC at pathological IIIB stage and higher.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has a specific antitumour activity against many malignant tumours. However, more than half of lung cancer cells are resistant to TRAIL-relevant drugs. Trichosanthin (TCS) is a traditional Chinese medicine with strong inhibitive effects on various malignancies. Nevertheless, its function on TRAIL resistance has not been revealed in non-small cell lung cancer (NSCLC). To examine the molecular mechanisms of TCS-induced TRAIL sensitivity, we administrated TCS to TRAIL-resistance NSCLC cells, and found that the combination treatment of TCS and TRAIL inhibited cancer cell proliferation and invasion, and induced cell apoptosis and S-phase arrest. This combined therapeutic method regulated the expression levels of extrinsic apoptosis-associated proteins Caspase 3/8 and PARP; intrinsic apoptosis-associated proteins BCL-2 and BAX; invasion-associated proteins E-cadherin, N-cadherin, Vimentin, ICAM-1, MMP-2 and MMP-9; and cell cycle-associated proteins P27, CCNE1 and CDK2. Up-expression and redistribution of death receptors (DRs) on the cell surface were also observed in combined treatment. In conclusion, our results indicated that TCS rendered NSCLC cells sensitivity to TRAIL via upregulating and redistributing DR4 and DR5, inducing apoptosis, and regulating invasion and cell cycle related proteins. Our results provided a potential therapeutic method to enhance TRAIL-sensitivity.
FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.
Objective To evaluate the clinical efficacy and prognostic factors of stereotactic body radiotherapy(SBRT)for pulmonary oligometastases,and to further explore the patients most suitable for SBRT. Methods From 2012 to 2105,51 patients with 76 oligometastatic lung tumors were treated with SBRT.In those patients,27 had primary lung tumors and the others had extrapulmonary tumors. Seven patients had squamous cell carcinoma,thirty-five had adenocarcinoma, and the rest had other types of cancer. The patients received radiotherapy at a dose of 50 Gy in five fractions or 60 Gy in three fractions. Survival analysis was made by the Kaplan-Meier method. A multivariate analysis was made by the Cox model. Results The 1-and 2-year local control rates were 86%(65/76)and 80%(61/76),respectively. The 1-and 2-year overall survival(OS)rates were 80%(41/51)and 55%(28/51),respectively. The median survival time was 30(2-57)months,while the median progression-free survival time was 8(1-32)months. Twenty-one patients had grade 1 radiation pneumonitis(RP),while one patient had grade 2 RP. The multivariate analysis revealed that no more than 2 oligometastatic lung tumors,progression-free interval(PFI), and a performance score(PS)no higher than 1 were independent factors for OS(all P<0.05). Conclusions SBRT is effective and safe for treating pulmonary oligometastases. The number of oligometastatic lung tumors,PFI,and PS are independent prognostic factors for OS. Suitable patients and the appropriate timing of treatment are key to the efficacy of SBRT.