Kai-Liang Wu

Electroacupuncture Improves Cognitive Function and Hippocampal Neurogenesis after Brain Irradiation.

Cognitive impairments after brain irradiation seriously affect quality of life for patients, and there is currently no effective treatment. In this study using an irradiated rat model, the role of electroacupuncture was investigated for treatment of radiation-induced brain injury. Animals received 10 Gy exposure to the entire brain, and electroacupuncture was administered 3 days before irradiation as well as up to 2 weeks postirradiation. Behavioral tests were performed one month postirradiation, and rats were then sacrificed for histology or molecular studies. Electroacupuncture markedly improved animal performance in the novel place recognition test. In the emotion test, electroacupuncture reduced defecation during the open-field test, and latency to consumption of food in the novelty suppressed feeding test. Brain irradiation inhibited the generation of immature neurons, but did not cause neural stem cell loss. Electroacupuncture partially restored hippocampal neurogenesis. Electroacupuncture decreased the amount of activated microglia and increased resting microglia in the hippocampus after irradiation. In addition, electroacupuncture promoted mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In conclusion, electroacupuncture could improve cognitive function and hippocampal neurogenesis after irradiation, and the protective effect of electroacupuncture was associated with the modulation of microglia and upregulation of BDNF in the hippocampus.

AB002. OS01.02. A phase ii study of chemotherapy concurrent with radiotherapy in patients with unresectable advanced thymic tumors

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China Background: Thymic malignancies are rare, and treatment options for unresectable thymic epithelial tumors (TET) are limited. We conducted a prospective phase II study of cisplatin plus etoposide concurrent with intensive modulated radiotherapy (IMRT) in patients with unresectable stage III or IV thymic epithelial tumors, to determine the efficacy and tolerability of the combination therapy. Methods: Patients were eligible if they had histologically confirmed unresectable thymic epithelial tumors, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or lower, measurable disease, and adequate organ function. No patient had previously undergone chemotherapy, radiotherapy, or surgery. Patients were treated with cisplatin (25 mg/m) and etoposide (75 mg/m) on day 1 to day 3 of a 4-week cycle for 2 cycles, concurrent with a median dose of 60 Gy (range, 40–66 Gy) thoracic IMRT. Two cycles consolidate chemotherapy was given after IMRT. The primary endpoint of this study was objective response rate (ORR), and the secondary endpoints included toxicity, progression free survival (PFS), and overall survival (OS). The trial was registered with ClinicalTrials.gov, number NCT02636556. Results: Forty-eight patients were enrolled, 31 with thymic carcinoma and 17 with thymoma. The median age was 52 years (range, 21–76 years), 24 patients (50%) were male. Sixteen patients had stage III disease, 14 patients had stage IVA, and 18 patients had IVB. The median number of chemotherapy cycles was 4 (range, 1–6). One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. The median follow-up times were 18 months [interquartile range (IQR) 9.5–31.5]. Of 30 assessable patients with thymic carcinoma, 23 (76.7%) had partial responses and 7 (23.3%) achieved stable disease. Of 16 assessable patients with thymoma, 12 (75%) had a partial response, 3 (18.8%) had stable disease, and 1 (6.3%) had progressive disease. The most common treatment-related adverse events were grade 1 and 2 neutropenia [27 (58.7%) of 46 patients], and grade 3 and 4 neutropenia [14 (32.6%) of 46 patients]. The other common acute toxicity was esophagitis in 39.1% of patients with RTOG grades 1–2, and in 2.2% with RTOG grade 3. RTOG grades 1–2 radiation pneumonitis developed in 36.9% of patients. Nine patients (19.6%) developed pulmonary fibrosis RTOG grade 1 or grade 2. The median PFS for all 46 patients was 24 months (95% CI, 12.66–35.34); similarly, the median PFS for patients with thymic carcinoma was 24 months (95% CI 15.92-32.08). The 3-year PFS was 37.3% for all 46 patients, and 35.4% for the patients with thymic carcinoma. The 3-year PFS was 51.1% for stage III patients, and 31.9% for stage IV patients. The 3-year OS was 73.8% for all the patients, and particularly, it was 62.2% for those with thymoma and 74.3% for those with thymic carcinoma. The 2-year local control rate and 2-year metastasis rate were 57.7% and 36.4% for all patients, respectively. Conclusions: These data suggest that the combination of cisplatin and etoposide with IMRT is highly effective and tolerable for the treatment of unresectable stage III and stage IV thymic epithelial tumors. Although advanced disease, we can acquire an excellent outcome of survival by the more positive concurrent chemoradiotherapy.

Thymic neuroendocrine tumors: an analysis of 18 cases and a literature review

Background: Thymic neuroendocrine tumors (TNETs) are exceedingly rare, and there are no uniform treatment strategies. Methods: Between September 1993 and March 2015, 18 patients diagnosed with histologically confirmed TNETs and treated at the Fudan University Shanghai Cancer Center were reviewed. Overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. The prognostic factors [sex, age, stage, tumor size (TS), grade, adjuvant therapy, and surgery status] for PFS and OS were analyzed. Results: Thirteen patients underwent surgical resection: 53.5% underwent complete tumor resection (R0), and 46.2% had a macroscopically residual disease (R2). Eleven patients received adjuvant treatment postoperatively [chemotherapy (CT) combined radiotherapy (RT), 7; RT, 3; and CT, 1]. Well-differentiated neuroendocrine carcinomas (n=12/18 patients; 66.7%); poorly differentiated neuroendocrine carcinomas (n=6/18 patients; 33.3%). Masaoka-Koga stages (MK) I, III, and IVb were observed in 1, 8, and 9 patients, respectively. The 5-year OS and 5-year PFS rates were 67.7% and 37.9%, respectively. The 5-year DFS rate in the patients with R0 resection was 66.7%. In univariate analysis, OS was significantly influenced by the grade (P Conclusions: Adequate surgical resection is a strong prognostic factor. Adjuvant RT contributes to controlling local recurrence (LR) to improve OS and PFS. Patients with well-differentiated TNET have a better OS. Additionally, an active treatment after recurrence will greatly benefit patients’ OS.