Preliminary study of intensity-modulated carbon ion reirradiation for locoregionally recurrent nasopharyngeal carcinoma after definitive IMRT——Clinical experience from Shanghai Proton Heavy Ion Hospital / 中华放射肿瘤学杂志

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.

The preliminary result of proton and carbon ion therapy for recurrent chordoma and chondrosarcoma of skull base and cervical spine / 中华放射医学与防护杂志

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.

Primary results of proton radiotherapy for 26 meningioma patients / 中华放射医学与防护杂志

Objective:To investigate the safety and efficacy of proton beam radiation therapy (PBRT) in patients with World Health Organization (WHO) GradeⅠ/Ⅱ meningioma.Methods:Twenty-six patients with intracranial ( n=8, 30.8%) or skull-base ( n=18, 69.2%) meningioma treated with PBRT from May 2015 to October 2018 were analyzed retrospectively. The median age of the cohort was 42 years (range 15-79 years). Eight patients had WHO Grade Ⅰ meningioma, and 9 had WHO Grade Ⅱ meningioma, respectively. Nine patients had clinical (radiological) diagnosis without histology. Seven patients received post-surgical PBRT (2 patients underwent Simpson Ⅰ-Ⅲ resection, 5 patients underwent Simpson Ⅳ-Ⅴ resection); 10 patients were irradiated for local recurrence after initial surgical resection. Results:All patients completed planned PBRT without break, and the median dose was 54 Gray-Equivalent (GyE) (range 50.4-60 GyE, 1.8-2 GyE/daily fraction). With a median follow-up of 22.2 (range 1.6-36.4) months, the 2-year overall survival and progression-free survival rates were both 100%. Grade Ⅰ skin erythema and alopecia were observed in 22 patients and Grade Ⅰ mucositis was observed in 2 patients. No acute of late toxicities of Grade 2 or above was observed.Conclusions:PBRT appeared to be a favorable treatment option for intracranial and skull base meningioma. Treatment-induced adverse effects and early response to PBRT were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

Dosimetric study of carbon ion radiotherapy for treating tumors at lacrimal system / 中华放射医学与防护杂志

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.

Dosimetric study of carbon ion radiotherapy for treating tumors at lacrimal system / 中华放射医学与防护杂志

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.

Preliminary study of pencil beam scanning proton and carbon ion therapy for chordoma and chondrosarcoma of head and neck / 中华放射肿瘤学杂志

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.

Early response and acute adverse effect after particle radiation therapy for adenoid cystic carcinoma of the head and neck / 中华放射医学与防护杂志

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.

Identification of differential inflammation factors in nephroblastoma tissue and clinical significance / 中华泌尿外科杂志

Objective To identify the differential inflammation factors in nephroblastoma tissue using proteomics technology and analyze its relationship with clinical stage,pathological phenotype,lymph node metastasis,vascular invasion.Methods From Jan 2010 to Dec 2014,nephroblastoma tumor tissues from 40 patients were obtained.Meanwhile,the 35 tissue near proximal kidney and 25 tissues distal kidney were also obtained.The classification of clinical stage included Ⅰ stage in 6 cases,Ⅱ stage in 12 cases,Ⅲ stage in 13 cases and Ⅳ stage in 9 cases.Other characters contained good prognosis type in 37 case,poor prognosis type in 3 cases,lymphatic metastasis in 17 cases,no sign of lymphatic metastasis in 23 cases,vascular invasion in 9 cases and non-vascular invasion in 31 cases.The SELDI-TOF-MS was used for screening differential protein peaks among three groups.Then,SPE and TRICINE-SDS-PAGE were used to separate and purificate the protein,which showed high peaks expression in tumor tissue,respectively.After in-gel digestion,we received the identification of targeted proteins according to sequence information through Nano-LC-MS/MS.Finally we compared differential expression of inflammatory peaks in different groups of clinical stage,pathological type,lymph node metastasis and vascular invasion.Results All the peaks high expression in tumor tissue,m/z12138 and m/z 13462 are identified as MIF and NAP-2.Expression of two protein peaks in tumor tissue(1437.8 + 997.3,1730.4 + 1147.8) is higher than those in proximal tissue (952.6 + 591.2,1031.1 + 1120.8) and in distal tissue(315.4 + 296.5,114.7 + 118.9),which showed the significant difference (P ＜ 0.001).According to the clinic stage classification,the expression of those protein were 678.8 + 189.0,746.2 + 238.7 in stage Ⅰ,664.0 + 202.0,1180.7 + 404.9 in stage Ⅱ,1524.7+407.9,2160.4 + 1252.3 in stage Ⅲ and 2850.2 + 861.2,2498.4 + 1290.5 in stage Ⅳ.Based on the other characters,expression of those protein were the 1271.7 + 809.2,1553.3 + 991.4 in good prognosis type,3487.2 + 166.2,3915.1 +507.3 in poor prognosis type,2207.1 +961.7,2569.5 + 1285.2 in lymph node metastasis,869.2 + 474.6,1110.2 + 433.6 in non-lymph node metastasis,2850.2 + 861.2,2498.4 +1290.5 in vascular invasion and 1027.8 + 521.3,1507.5 + 1019.9 in non-vascular invasion.All the comparison results have significant statistical difference (P ＜ 0.001).Conclusion MIF and NAP-2significantly increase in nephroblastoma tumor tissue.Meanwhile,there was obvious relationship between those protein with clinical stage,pathological type,lymph node metastasis and vascular invasion.