Objective To investigate EBT3 and EDR2 film responses to different linear energy transfers ( LETs) and doses from carbon ion beams. Methods EBT3 and EDR2 films were calibrated by two methods. In the first method, films were placed at the same depth within a phantom and irradiated by beams with different parameters such as beam energy. In the second method, films were separately placed at different depths in a phantom and irradiated by the same beams. These methods were used to irradiate films with ions of different LETs. Results For EBT3 film, the dose calibration curves correlated with different LETs appeared to be typical hyperbolic curves with a maximum difference between the curves of ± 17％ (1σ). Meanwhile, the shape of the dose calibration curves for EDR2 film appeared to be linear. The values along all these curves were within ± 27.4％ (1σ) of the value for the average curve. The dose responses of both films were inversely proportional to LETs. The sensitivity of EBT3 film was inversely proportional to the dose, while the sensitivity of EDR2 film showed no relationship with the dose. Conclusions Influenced by the dual factor of LET and dose, the application of EBT3 film was limited in carbon ion. However, without no dose dependence, EDR2 film could be used to measure dose distributions created by single LET carbon ion beam.

Objective To investigate the dosimetric advantages of proton and heavy ion radiotherapy ( particle radiotherapy) for liver cancer adjacent to gastrointestinal tract. Methods Ten patients with liver cancer adjacent to gastrointestinal tract receiving radiotherapy were recruited in this study. The prescription was first given with 50 Gy ( RBE )/25 fractions to planning target volume 1 ( PTV-1 ) using proton irradiation,and then administered with 15 Gy ( RBE)/5 fractions to PTV-2 using carbon-ion irradiation. A simultaneous integrated boost regime was established using the same variables and prescription. The organ at risk ( OAR) constraints were referred to RTOG 1201. All plans were performed for dose evaluation after qualifying the OAR constraints. Results The dose coverage of 95％ of the prescribed dose ( V95) for PTV-1 from the photon plan (97.15％±4. 27％),slightly better than (96.25±6. 69％) from the particle plan (P=0. 049).The V95 of PTV-2 from the particle plan was (94.6％±6. 22％),comparable to (95.12％±3. 49％) from the photon plan (P=0. 277).The integral dose of Body-PTV-1 delivered by the particle plan was merely 39. 9％ of that delivered by the photon plan. The mean liver-GTV dose from the particle plan was only 81. 8％ of that from the photon plan. The low-dose irradiation to the stomach and duodenum from the particle plan was significantly lower than that from the photon plan. Conclusions The dose to the liver-gross tumor volume ( GTV) is the main factor limiting the increase of total dose to the tumors. When the absolute GTV in the liver is relatively large,particle radiotherapy can maintain comparable dose coverage to the tumors as the photon radiotherapy whereas significantly reduce the dose to the liver-GTV.

Objective To measure the CT Hounsfield Unit ( HU) and relative stopping power ( RSP) conversion curve. Methods In this study, the RSPs of 12 different tissue equivalent rods were measured with proton and carbon beam in the Shanghai Proton and Heavy Ion Center ( SPHIC) . The same tissue equivalent materials were scanned with CT scanner to acquire the HU. Results Conversion curve for the transformation of HU into RSP was generated for both proton and carbon ion beam. Differences between RSPs measured using proton and carbon beam were ≤0. 64%except lung material. Conclusions A RSP versus HU conversion curve was generated for both protons and carbon ions.

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 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 investigate a system for the detection of the acoustic signal created by clinical proton and carbon ion Bragg-peaks (BPs).Methods An acoustic detector was attached to water phantoms downstream of the beam.The water-equivalent depth of this phantom was measured by a peakfinder (PTW,Siemens,Germany) using high energy proton beams.By maintaining the same particle number,either the BP to detector distance (BTD) or beam intensity was changed to investigate their relationships with the magnitude of acoustic signal.By moving the beam spot in lateral directions,the full width at half maximums (FWHMs) of BPs was measured and compared.Results The detected acoustic signal created by beam on or beam off could represent the magnitude of signal,which was proven by a statistical analysis.The magnitude of acoustic signals created by proton BPs were inversely proportional to BTD,but proportional to intensities.The measured FWHM of 125.43 MeV proton BP was 11.7％ larger than data from the treatment planning system (TPS).Carbon ion showed similar result whereas the measured FWHM of 178.89 MeV/u carbon ion BP was 45.6％ larger than the data from TPS.The BTDs could be more than 67.7 mm while maintaining enough magnitude of acoustic signal.Conclusions This acoustic detection system can detect the acoustic waves from clinical proton and carbon ion BPs.However,further investigation is ongoing to decrease the noise.

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 investigate the effect of lipiodol as embolization agents in liver, after transcatheter arterial chemoembolization, on dose calculation under the carbon ion treatment plan. Methods: The actual relative linear stopping powers(RLSP)in pure lipiodol, pure gel and lipiodol-gel mixture, together with the correctd RLSPs from their CT images, were compared.In seven typical cases with lipiodol deposition area, carbon ion treatment plan was performed for the original lipiodol images.Successively on the basis of analysis that has made, the RLSP in lipiodol deposition area was corrected to be as in normal liver tissue, for which the carbon ion treatment plan was again performed.A comparison was made of differences in water equivalent depth (WED) and dose distribution on different CT images. Results: The RLSP value corrected according to CT image HU value, lipiodol, and lipiodol-gel mixture may increase by 4.6%-139.0% compared with the measured value. In seven typical cases, deposited lipiodol can cause WED to increase by (0.89±0.41) cm along the field track and RBE by(3.83±1.71)Gy within the 1 cm of distal area of target. Conclusions In order to improve the accuracy of dose distribution calculation, the HU value and/or RLSP in deposited lipiodol area in liver after transcatheter arterial chemoembolization should being corrected to be as in the normal liver tissue.

Objective: To evaluate the dosimetric difference between carbon ion radiotherapy and photon radiotherapy for treating tumors at lacrimal system. Methods: Using the CT images of 10 patients with tumors at lacrimal system, the carbon ion plan, the photon volume intensity modulation plan (VMAT) and the fixed wild photon intensity modulation radiotherapy (IMRT) plan were generated. The prescription was 54 Gy(RBE) in 18 fractions for clinical target volume (CTV) and 63 Gy(RBE) in 18 fractions for CTV-boost. Dosimetric differences of organ at risks were compared based on the same planning target volumes (PTVs) with similar dose coverages. Results: There was no statistically significant difference in the PTV coverage among three plans (P>0.05). Compared to VMAT and IMRT plans, carbon ion plans reduced the mean doses of eyeballs, mean doses and near-maximum doses of optical nerves of both ipsilateral ( t=7.35, 3.79, 4.66, 8.48, 2.52, 2.76, P<0.05) and contralateral eyes (t=3.87, 10.49, 9.16, 4.43, 6.53, 5.12, P<0.05), while the mean dose of brain was decreased from(5.65±3.58) and (5.76±2.09)Gy(RBE) to (0.81±0.90)Gy(RBE) (t=6.76, 17.33, P<0.05). Conclusions Compared to photon VMAT or IMRT, carbon ion could reduce the doses to optical critical organs around tumors. Thus, carbon ion radiotherapy has potential to reduce patients′ radiation related side-effects.