Objective To evaluate the safety and efficacy of proton and carbon-ion radiotherapy (RT) for stage Ⅰ non-small cell lung cancer (NSCLC) with pencil beam scanning technique.Methods From August 2014 to December 2015,10 patients with stage Ⅰ NSCLC who were inoperable or refused surgery were treated by proton +/-carbon-ion RT.Primary lesions were irradiated using 2-4 portals with 45-degree beams.A total dose of 50-70 GyE/10 fractions,60-64 GyE/15-16 fractions,and 66-72 GyE/22-24 fractions were administered to patients based on tumor location (4 peripheral,3 middle,and 3 central lesions,respectively).Results At the last follow-up in December 2016 with the median follow-up of 18.1 (11.9-28.1) months,local control was found in all patients per CT or PET/CT scanning(6 complete response,3 partial response,and 1 stable disease).However,2 patients with local control (1 partial response and 1 stable disease) experienced a distant failure at 8.7 and 24.9 months after RT,respectively.There was no RT-related Grade 3-5 toxicity in all patients.Grade 2 toxicities were only found in 2 patients (acute skin reaction and leucopenia,respectively).At 1,3-5 months after RT,the pulmonary function tests showed a slightly increase in FVC,FEV1 and DLCO-sb compared with those before RT without statistical significance (P ＞ 0.05).Conclusions The particle RT using pencil beam scanning technique was safe,and yielded encouraging outcome for patients with stage I NSCLC who were inoperable or refused surgery.Further follow-up and prospective clinical studies are warranted in the future.

We designed and constructed a fuse expression gene OAAT and staphylococcal enterotoxin A (SEA) on the basis of the OAAT designed and constructed which consists of the structural protein VP1 genes from serotypes A and O FMDV, 5 major VP1 immunodominant epitopes from two genotypes of Asia1 serotype, and 3 Th2 epitopes originating from the non-structural protein, 3ABC gene and structural protein VP4 gene. The recombinant plasmids pEA was constructed using SEA as a genetic adjuvant. Expressions of target gene from the pEA in Hela cell were verified by IFA and Western blotting. The experiment of BALB/c mice immunized with the DNA vaccines showed that pA and pEA could induce simultaneously specific antibodies against serotypes A, Asia1, and O FMDV, and the highest antibody titres were found in the pEA and inactivated vaccine groups compared to pA vaccinating mice. Compared with the control, the levels of IL-2, IFN-gamma, IL-4, and IL-10 expression by splenic lymphocytes from mice immunized with pA and pEA were significantly increased. In addition, we found that the levels of IL-2, IFN-gamma and IL-4 from the mice immunized with pEA was higher than mice immunized with pA did. The results of viral challenge in guinea pigs showed the pA, pEA and inactivated vaccine provided full protection in 2/4, 2/4, 3/4, 3/4 and 4/4, 4/4 guinea pigs from challenge with FMDV O/NY00 and Asial/YNBS/58, respectively. The results demonstrated fuse protein OAAT and SEA may be potential immunoge against FMDV, furthermore, SEA may be an effective genetic adjuvant for DNA vaccine.
Adjuvants, Immunologic ; genetics ; Animals ; Antigens, Viral ; immunology ; Capsid Proteins ; genetics ; immunology ; Enterotoxins ; genetics ; immunology ; Epitopes ; immunology ; Foot-and-Mouth Disease ; immunology ; prevention & control ; Foot-and-Mouth Disease Virus ; immunology ; Guinea Pigs ; HeLa Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Peptide Fragments ; genetics ; immunology ; Vaccines, DNA ; immunology ; Viral Structural Proteins ; genetics ; immunology ; Viral Vaccines ; immunology

Objective To observe the short-term effect and toxicities after carbon ion radiotherapy (CIRT) for tracheal adenoid cystic carcinoma (TACC).Methods From March 2016 to October 2017,a total of 10 patients with TACC were treated using CIRT.Among them,three patients had recurrent disease (two after surgery,and one after brachytherapy),one received bronchoscopic cryosurgery for stage Ⅰ disease,and the other 9 had locally advanced disease (3/6 received endoscopic treatment before CIRT).All patients received CIRT using pencil-beam scanning technique.Except that the patient with recurrent disease after brachytherapy received 60 GyE/20 Fx,the patient received cryosurgery and one recurrent patient after surgery received 66 GyE/22 Fx,all other patients received 69 GyE/23 Fx.Results The median follow-up time was 5.5 (1.5-16.4) months.Among the 9 patients with gross tumors,3 patients achieved complete response,2 achieved partial response,and 4 remained stable disease per RECIST 1.1 criteria.The postcryosurgery patient remained no evidence of disease.Except 1 patient experienced grade 4 tracheal stenosis,no other grade ≥ 3 adverse effects were observed.Grade 2 acute toxicities included 1 hoarseness and 1 neutropenia,both relieved after CIRT.Hypothyroidism in one patient was the only observed grade 2 late toxicity.Conclusion CIRT is safe and effective in the management of TACC during a short-time observation.

Objective:To compare dose distributions between photon versus proton and carbon ion radiotherapy (particle therapy, PT) among patients with gross tumors, and to evaluate the safety and efficacy of PT for thymic malignancies (TM).Methods:From Sept 2015 to Aug 2018, 19 patients with TM who underwent non-palliative PT using pencil beam scanning technique in our hospital and had at least one follow-up were retrospectively analyzed. Diseases staged from Ⅰ-Ⅳ B including 15 Ⅲ-Ⅳ B. All the patients had pathological diagnosis with 10 thymomas, 6 carcinomas and 3 neuroendocrine tumors of the thymus. A set of dosimetric comparisons were conducted in patients with gross tumors at a total dose of 66 GyE, in 33 fractions for photon or proton beams and in 22 fractions for carbon ion beams. Five patients without any local treatment and 7 patients after R2 resection received radical radiotherapy of proton 44.0-48.4 GyE in 20-22 fractions plus carbon ion 21.0-23.1 GyE in 7 fractions, 1 case after complete resection (R0 resection) had proton 45 GyE in 25 fractions, 5 cases after R1 resection had proton 60.0-61.6 GyE in 28-30 fractions and 1 case of recurrence after postoperative radiotherapy had only carbon ion 60 GyE in 20 fractions. Results:The median follow up time was 19.0 (2.4-42.9) months. There were 13 patients with gross tumors, with a median largest diameter of 5.7 (2.7-12.8) cm. The dosimetric study showed that proton and carbon-ion plans significantly reduced the maximum dose to the spinal cord, the mean doses to the organs at risk (OARs) including the lung/heart/esophagus, and the integral dose of the exposed area about 25%-65% compared to photon plans. No other toxicities ≥ grade 3 were observed except one myocardial infarction (grade 4 late toxicity). There was no local failure observed. Metastasis to regional lymph node, lung, pleura, skull base, bone or liver occurred in 4 patients with Ⅲ-Ⅳ B stage disease in 6.1-22.8 months after treatment. The 2-year local control and overall survival rates were 100%, disease free survival and distant metastasis free survival rates were 64.6%. Conclusions:For TMs, PT has significant advantages over photon in terms of sparing OARs, and is safe and effective in patients with TMs after short-time follow-up.

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Objective: To investigate the inhibitory effect of recombinant oncolytic adenovirusAd-Apoptin-hTERTp-E1A(ATV) on luciferase-labeled human lung cancer cells (A549-luc) and human lung cancerA549 cells, and to compare the differences in the inhibitory effect on two cell lines. Methods:ATV was used to infectA549-luc cells andA549 cells respectively. WST-1 and crystal violet staining were used to determine the difference in the inhibitory effect of ATV. Hoechst and Annexin V-FITC/PI staining were used to verify the inhibition mode ofATV. Results: WST-1 and crystal violet staining showed thatATV had significant inhibitory effect on bothA549-luc and A549 cells ( P <0.05). ATV showed significant inhibitory effect on both cells at 24, 48 and 72 h ( P <0.05 or P <0.01), and reached the peak at 72 h; ATV at concentrations of 1, 10 and 100 MOI all showed inhibitory effect on both cells, and reached the peak at 100 MOI. Hoechst staining showed that A549-luc cells and A549 cells infected with ATV showed typical nuclear fragmentation and marginal set. The results of Annexin V-FITC/PI Flow cytometry showed that ATV infection resulted in apoptosis of A549-luc and A549 cells, which was in a time-dependent manner and reached the peak at 72 h( P <0.05 or P <0.01). Conclusion: Insertion of luciferase didn’t significantly change the inhibitory effect and inhibitory mode ofATV onA549-luc cells.ATV exerted its in vitro inhibitory effect onA549-luc and A549 cells by inducing cell apoptosis.

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.