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 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 investigate the expression of programmed death ligand 1 (PD-L1) in rectal cancer tissues and the correlation of PD-L1 expression with clinicopathological characteristics and overall survival of patients.Methods:The clinical data of 200 newly treated rectal cancer patients in Shanxi Provincial Cancer Hospital from January 2014 to December 2015 were retrospectively analyzed. The expression of PD-L1 in rectal cancer tissues was detected by immunohistochemistry. The correlations of PD-L1 expression with gender, age, tumor T stage, lymph node metastasis, tumor differentiation, histological type, tumor TNM stage, neutrophil-to-lymphocyte ratio (NLR) and overall survival of patients were analyzed.Results:The positive expression rate of PD-L1 was 24% (48/200). The positive expression rate of PD-L1 was high in patients with lymph node metastasis and high NLR (≥ 3.5) (both P < 0.05). The 5-year overall survival rate in PD-L1-positive group was 42%, and the PD-L1-negative group was 59%, and the difference between the two groups was statistically significant ( P < 0.05). The results of multivariate analysis showed that lymph node metastasis ( HR = 3.456, 95% CI 2.148-5.556, P < 0.01), NLR ≥ 3.5 ( HR = 1.871, 95% CI 1.169-2.996, P = 0.009), and PD-L1-positive expression ( HR = 2.187, 95% CI 1.373-3.484, P = 0.001) were independent adverse influencing factors for the overall survival of rectal cancer patients. Conclusion:PD-L1 is highly expressed in rectal cancer tissues, and the positive expression of PD-L1 is associated with poor overall survival of patients.

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 evaluate the dose variation of target coverage and organs at risk ( OARs) among four planning strategies using spot-scanning carbon-ion radiotherapy for non-small cell lung cancer ( NSCLC) . Methods Ten NSCLC patients utilizing gating motion control were selected to receive dose calculation over multiple acquired 4DCT images. Four optimizing strategies consisted of intensity-modulated carbon-ion therapy ( IMCT-NoAS ) , IMCT combined with internal gross tumor volume ( IGTV ) assigned muscle ( IMCT-ASM ) , single beam optimization ( SBO ) ( SBO-NoAS ) and SBO combined with IGTV assigned muscle (SBO-ASM).The initial plan was re-calculated after the 4DCT data were reviewed and then compared with the initial plan in the dosimetry. Results For re-calculation plans with two reviewing CTs,all four strategies yielded similar planning target volume ( PTV ) coverage. Merely IMCT-NoAS strategy presented with relatively significant variations in dose distribution. Dose variation for OARs between initial and re-calculated plans:for all four strategies,V20 of ipsilateral lung was increased by approximately 2. 0 Gy (relative biological effective dose,RBE),V30 of heart was increased by approximately 1. 0 Gy (RBE) for both IGTV assigned muscle strategies,whereas decreased by approximately 0. 2 Gy ( RBE) for both IGTV non-assigned muscle strategies. The maximum dose of spinal cord was changed by 2. 5 Gy ( RBE ) . Conclusions Carbon-ion radiotherapy is sensitive to the anatomic motion within the tumors along the beam path. When the tumor motion along the head-foot (H-F) direction exceeds 8 mm,SBO-ASM strategy provides better dose coverage of target. Strategies with IGTV assignment may result in dose overshoot to a position deeper than the initial planning dose distribution.

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 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.