Objective To establish a rat model of radiation-induced optic neuropathy ( RION) by delivering a single radiation dose to the optic chiasm. The aim of our study was to analysis the feasibility and effectiveness of manganese-enhanced magnetic resonance imaging ( MEMRI) in RION. Methods 34 Wistar rats were randomized to the control group(4 rats), the 2-month group(5 rats),the 4-month group(4 rats) and the 6-month group(11 rats) according to the different feeding period after irradiation. MEMRI scan were performed when the respective feeding periods of all groups expired. The rats were then killed for histological studies with hematoxylin and eosin stain, Luxol Fast Blue stain, and electron microscopy analysis. Results The ratio of RION in the four groups were 0/3, 1/5, 2/4 and 11/11, respectively (χ2 =15?443, P<0?05). There was an inverse correlation between the relative optical density value in the LFB stain and the interval between irradiation and pathological examination(R= -0?643,P<0?05). The number of glial cells in the HE stain in the four groups were 194 ± 65, 234 ± 19, 124 ± 11 and 345 ± 98, respectively(R=0?590,P<0?05). When compared MEMRI scan with the corresponding histological examination, we found that there was loss of signals of optic nerve on MEMRI imaging in one of 5 rats in the 2-month group, while no significant histological difference was found between this rat and the others. Conclusions RION can be non-invasively detected and semi-quantitative analysed by MEMRI scan. Moreover, RION can be early diagnosed by MEMRI scan which is capable to show physiological change in advance of pathological change.

Objective To study the early response and acute/subacute adverse effects after particle radiation therapy for adenoid cystic carcinoma (ACC) of the head and neck.Methods Between May 2015 and March 2016,a total of 8 patients with ACC of the head and neck were treated using proton and/or carbon-ion radiation therapy.Three patients had early stage and 5 had locally advanced disease.Five patients had an R2 and three achieved an R1 resection.Results Seven patients received intensitymodulated proton therapy (IMPT) followed by intensity-modulated carbon-ion therapy (IMCT) boost.One patient received IMPT only.Among the five patients who had an R2 resection,2/3 patients had partial response (PR)/stable disease (SD) at the end of radiation,0/3 achieved PR/complete response (CR) at 1-month follow-up,and 1/2 achieved PR/CR at 3-months' follow-up after the completion of radiation,respectively.Two patients experienced Grade Ⅲ mucositis during radiation therapy.No patient experienced moderate or severe skin reactions.At the time of this analysis,all patients are alive and no patient had disease progression or recurrence.Conclusions The short-term outcomes indicated that particle therapy is safe and potentially efficacious in the management of head and neck ACC.However,longer follow up is needed to assess late toxicities and long-term efficacy.

Background:After deifnitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma (NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiifcant challenges for locally recur-rent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recur-rent NPC. However, only patients with small-volume tumors can beneift from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy (IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radio-resistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy (CIRT). In addition, CIRT is a high linear energy transfer (LET) radiation and provides an increased relative biological effectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 GyE (gray equivalent), at 2.5 GyE per daily fraction, was well tolerated in patients who were pre-viously treated for NPC with a deifnitive dose of IMXT. The short-term response rates at 3–6months were also accept-able. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemo-therapy to CIRT can beneift locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneifts of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results. Methods and design:The maximal tolerated dose (MTD) of re-treatment using raster-scanning CIRT plus concur-rent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 GyE (2.5 GyE×21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Effcacy in terms of overall survival (OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%. Conclusions:Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate effcacy but causes potentially severe toxicities. Improved outcomes in terms of effcacy and toxicity proifle are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemo-therapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Objective To evaluate the short-term efficacy and adverse events of pencil beam scanning proton and carbon ion therapy in the treatment of chordoma and chondrosarcoma of the head and neck.Methods Between July 2014 and July 31,2017,61 patients with chordoma and chondrosarcoma of the head and neck receiving proton and heavy ion therapy as the first course of radiotherapy were enrolled.Among them,45 patients were diagnosed with chordoma and 16 cases of chondrosarcoma,39 male and 22 female.The median age was 38 years old (range:14-70 years).The median maximum tumor diameter was 4.1 cm (range:0-8.6 cm).The clivus and the cervical spine were the primary tumor sites.Results Eight patients received proton therapy,21 patients were treated with proton combined with carbon ion therapy and 32 patients received carbon ion therapy.All patients successfully completed the planned radiotherapy.The medial follow-up time was 21 months (range:7-47 months).No grade 3-4 acute toxicity was observed.Only one patient suffered from radiation-induced temporal lobe injury.The 2-year progression-free survival (PFS)and overall survival (OS) were 91％ and 100％.Conclusions Pencil beam scanning proton and heavy ion therapy yields relatively favorable short-term outcomes in the treatment of chordoma and chondrosarcoma of the head and neck.Nevertheless,the long-term clinical efficacy and safety remain to be investigated during follow-up.

Objective:To evaluate the short-term tumor control and toxicity of recurrent skull base and cervical spine chordoma and chondrosarcoma in patients treated with pencil beam scanning proton and heavy ion therapy.Methods:Between June 30 th, 2014 and July 30 th, 2018, a total of 45 skull base and cervical spine chordoma ( n=39) and chondrosarcoma ( n=6) patients (28 males and 17 females; mean age at initial presentation of 44 years, range, 14-76 years) were treated in our center for the course of radiotherapy. The median maximum tumor volume was 57 cm 3 (range, 6.6-231.7 cm 3). There were 31 post-operative recurrent patients and 14 post-operative and post-radiated recurrent patients. One patient received proton therapy, 21 patients received combined proton and carbon ion therapy, 23 patients received carbon ion therapy. Results:All patients completed the whole course of the treatment. The median follow-up time was 29 months (range: 8-57 months), the 2-year overall survival (OS), local control (LC), and progression-free survival (PFS) were 82.7%, 85.3%, and 73.8%, respectively. There were no other grade 3-4 acute or late radiation-induced toxicity except one grade 3 acute mucositis. The 2-year OS rates for patients after first-time radiation vs. re-irradiation were 96.2% and 50.3% ( χ2=16.969, P<0.05). Conclusions:The short-term outcomes of pencil beam scanning proton and heavy ion therapy for recurrent skull base and cervical spine chordoma and chondrosarcoma is favorable. Further study is needed for long-term efficacy and safety.

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.

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.

BACKGROUNDNasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China. The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU) is considered to be the standard treatment for NPC. However, its clinical use is limited by its toxicity. Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.

METHODSMedline, the Cochrane library, and the Chinese medical literature database were searched for eligible studies. Meta-analysis was performed using Review Manager (Version 5.2).

RESULTSSix random controlled trials (RCTs) including 514 patients met our criteria. Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades III-IV, liver and kidney impairment grades I-II, and radiodermatitis grades III-IV versus the conventional regimen of CCRT with 5-FU and platinum, while the longterm effectiveness rate of overall survival, locoregional failure-free survival, or distant metastasis failure-free survival between the two groups was therapeutic equivalence.

CONCLUSIONSThe regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT. However, we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare, analyze, and confirm the findings.

Carcinoma ; Chemoradiotherapy ; Fluorouracil ; administration & dosage ; therapeutic use ; Humans ; Nasopharyngeal Neoplasms ; drug therapy ; Platinum ; administration & dosage ; therapeutic use ; Taxoids ; administration & dosage ; therapeutic use ; Treatment Outcome

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.