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 test the usefulness of PET-range verification (RV) method for proton radiation accuracy verification in poly (methyl methacrylate) (PMMA) phantom using off-line PET/CT scanning.Methods:Proton irradiation dose of 2 Gy and 4 Gy were delivered in PMMA phantom. Given the difference of clinical target volume (CTV), 7 subgroups with different depth (5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0 cm) were set for each dose (14 radiation plans or radiation fields). PET/CT scan was performed 10 min after irradiation of 48-221 MeV proton beam. A co-registration between CT from treatment planning system and PET/CT was performed, as well as the smoothing and normalization of PET/CT data. The region of interest (ROI) and profile lines were drawn with the Raystation PET-RV software. The predictive induced radioactivity and the measured induced radioactivity profile lines were analyzed to evaluate the Δ R50, namely, the error at the position corresponding to 50% of the maximum predictive induced radioactivity at the end of both curves. Results:The size of each ROI was 5.0 cm×5.0 cm×2.5 cm. Profile lines were evenly distributed with the interval of 3 mm, and totally 289 pairs of profile lines were drew. The 2 Gy- and 4 Gy-dose groups yielded similar mean depth errors (Δ R50 between 1 mm and -1 mm with a standard deviation <1 mm). Conclusions:The off-line PET/CT scanning of PMMA phantom reveals a good agreement between predicted and measured PET data, with error of ±1 mm. The PET-RV method can be extended to clinical cases′ verification in human body treatment with further investigation.

Objective    To describe the effect of sequential pulmonary balloon angioplasty for patients with chronic thromboembolic pulmonary hypertension, who was accompanied with progressed pulmonary hypertension after pulmonary endarterectomy surgeries. Methods    From 2014 to December 2017, 7 patients were treated with a combination therapy of pulmonary endarterectomy and sequential pulmonary balloon angioplasty. There were 1 male and 6 females at age of 58 (43–59) years. A follow-up period of more than 1 year was accomplished. The result of right sided heart catheterization and ultrasonic cardiogram between and after the pulmonary endarterectomy or balloon angioplasty was collected. Results    Seven patients were treated with a combination of pulmonary endarterectomy and sequential pulmonary balloon angioplasty, which included 1 patient of single pulmonary balloon angioplasty and 6 patients of multiple pulmonary balloon angioplasties. The balloon dilation times was 2 (2–6), and the number of segments during each single balloon dilatation was 3–5, compared with the first clinical results before  the first balloon dilation, systolic pulmonary artery pressure [53 (47–75) mm Hg vs. 45 (40–54) mm Hg, P=0.042), mean pulmonaryartery pressure [38 (29–47) mm Hg vs. 29 (25–39) mm Hg, P=0.043], N terminal-B type natriuretic peptide [1 872 (1 598–2 898) pg/ml vs. 164 (72–334) pg/ml, P=0.018] improved significantly after the last balloon angioplasty. Heart function classification (NYHA) of all the 7 patients were recovered to Ⅰ-Ⅱclasses (P<0.05). Conclusion    Sequential pulmonary balloon angioplasty after pulmonary endarterectomy can further reduce the patient's right heart after load, improve the heart function for patients with progressed pulmonary hypertension after pulmonary endarterectomy surgeries.

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 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.

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.

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.

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.

Objective: To summarize the peri-operative management experience of pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 56 CTEPH patients received PEA in our hospital from 2015-01 to 2016-11 were retrospectively analyzed. Our study was focused on the medication in respiratory and circulatory system during ICU stay, peri-operative application of vasoactive drug and target drug to pulmonary hypertension (HP), usage of ventilators, mechanical assisted devices and other management experiences. Results: No peri-operative death occurred. There were 2/56 (3.6%) patients with lung reperfusion, 2 (3.6%) with PH crisis. Compared with pre-operation, the post-operative pulmonary artery hemodynamics parameters were improved as right heart catheter measured pulmonary artery systolic pressure (PASP) decreased from (85.05±22.40) mmHg to (36.83 ±17.21) mmHg and pulmonary vascular resistance decreased from (773.84±342.95) dyn·s·cm-5 to (293.59±214.95) dyn·s·cm-5. Post-operative oxygen saturation was maintained at (95-100) % in all patients. Echocardiography found that PASP from pre-operation (85.03±25.78) mmHg decreased to (39.44±19.24) mmHg at follow-up period, P<0.01.Conclusion: A comprehensive peri-operative management of PEA was helpful to improve pulmonary hemodynamics in CTEPH patients; meanwhile, effective prevention and treatment of severe complication could obviously reduce peri-operative mortality.

To perform an evaluation of the on-going prospective clinical trials on particle radiation therapy and their impact on the current clinical practice as well as future clinical research and development.Furthermore,to briefly present the results of the registration trial of the IONTRIS particle therapy system at the Shanghai Proton and Heavy Ion Center.We used data from the clinicaltrials,gov and the Particle Therapy Collaborative Organization Group (PTCOG) website.After excluding retrospective and in silico studies,we examined and analyzed the prospective clinical trials for their ion type,targeting disease site,and nature.At the time of this analysis,149 prospective trials were identified on proton and carbon-ion radiation therapy,including 20 were carbon-ion and 129 trials were proton radiation focused,respectively.Except for 15 randomized phase Ⅱ/Ⅲ and Ⅲ trials,134 trials were phase 0-Ⅱ trials.Tumors from nearly all body parts were covered by the on-going trials,but trials on pediatric,GI,lung,prostate,and breast cancer account for the majority.The majority of the currently on-going trials focus on the efficacy and adverse-effects of the new dose/fractionation schemes of particle therapy as well as the use of particle therapy on new indications.Few studies invcstigate the addition of adjuvant therapy or imaging technology used in adjunct with particle therapy.Randomized trials that compare particle radiation therapy versus photon radiation is relatively uncommon.Despite the prevailing use of proton and heavy-ion radiation therapy for cancer treatment,～ 150 prospective clinical trials associated with particle radiation therapy are identified.As the majority of trials aim to investigate more efficacious dose/fractionation and the application of particle therapy on new indications,improved outcome from and expanded utilization of particle radiation therapy can be expected.