质子碳离子笔形束扫描技术治疗Ⅰ期非小细胞肺癌的初步结果

目的 在国内首次报道采用质子碳离子射线治疗Ⅰ期非小细胞肺癌（NSCLC）的近期疗效和不良反应。方法 2014年8月至2015年12月,共收治10例病理证实的Ⅰ期NSCLC患者。使用IONTRIS设备笔形束扫描技术,通过可以调节能量的点扫描、实现对靶区更加适形的目的,2~4个射野给予质子和碳离子放疗。根据肿瘤部位给予不同分割方式照射,4例周围型接受 50~70 GyE/10次放疗,3例中间型60~64 GyE/15~16次,3例中央型66~72 GyE/22~24次。结果 中位随访时间为18.1（11.9~28.1）个月,最后一次随访时患者均存活。10例患者局部控制率100%,其中6例患者完全缓解,3例部分缓解,1例疾病稳定;2例放疗后随访中出现远处转移。放疗开始3个月内,无3级及以上放疗相关急性不良反应发生。随访期内未观察到2级及以上的晚期不良反应。放疗后1和3~5个月肺功能（最大通气量、第1秒通气量及CO弥散量）与放疗前相比略有上升,差异无统计学意义（P>0.05）。结论 对Ⅰ期非小细胞肺癌患者,质子碳离子笔形束扫描技术治疗短期随访结果安全、有效。     

26例脑膜瘤的质子放射治疗初步临床结果

目的 考察质子射线放射治疗世界卫生组织（WHO）Ⅰ/Ⅱ级脑膜瘤的初步疗效及不良反应。方法 回顾性分析2015年5月至2018年10月上海市质子重离子医院治疗脑膜瘤患者26例,其中18例为颅底脑膜瘤。患者的中位年龄为42岁（范围15~79岁）。病理诊断为WHOⅠ级脑膜瘤的患者8例,病理诊断为WHO Ⅱ级的脑膜瘤患者9例,影像学诊断患者9例。7例患者为术后放疗（Simpson Ⅰ~Ⅲ级切除2例,Simpson Ⅳ~Ⅴ级切除5例）,10例患者为术后复发后放疗。结果 中位随访时间为22.2个月,所有患者均完成了既定的质子射线放射治疗,中位等效剂量为54 GyE（范围50.4~60 GyE）, 单次剂量为1.8~2.0 GyE。治疗后70%患者症状部分缓解,2年无进展生存率（PFS）和总生存率（OS）均为100%。治疗期间急性放射反应轻微,仅出现1级脱发（n=22）和黏膜反应（n=2）,无2级及以上急性反应,目前尚未观察到晚期不良反应。结论 质子治疗颅内及颅底脑膜瘤安全有效,长期疗效及不良反应需进一步随访。     

胸腺肿瘤长期跟踪观察预后因素探讨

作者报道了该院1967～1984年收治的108例胸腺肿瘤患者的治疗效果,分析其预后因素。其中手术加术后放疗94例,单纯放疗8例,手术或/和放疗后复发再治疗者6例。治疗方法:对Ⅰ、Ⅱ期及大部份Ⅲ期病例行胸腺全切术,其余的行次全切除或仅作探查术;放疗用高能X线、~(60)Coγ线,胸前单野照射,40Gy/4W;对Ⅲ期以上仅作次全切除病例,前后二野对穿照射,有的病例追加6～16Gy/1～2W。观察期最长达20年,最短2年。结果表明,Ⅰ、Ⅱ期及Ⅲ期胸腺全切者,10年生存率为88%;Ⅲ、IV_b期行次全切除或探查术加放疗且无复发者,10年生存率为62%;Ⅳ期无一例生存5年。死亡原因主要是肿瘤复发,而重症肌无力(以下简称MG)或其他并发症致死者少见。肿瘤的复发及     

质子碳离子治疗腺样囊性癌的近期疗效及不良反应

目的 观察束流调强粒子放射治疗头颈部腺样囊性癌的不良反应和近期疗效。方法 2015年5月至2016年3月,8例初治的病理证实的头颈部腺样囊性癌患者,5例患者为局部晚期（T_3-4期）,3例患者为R1切除,5例患者为活检术后或R2切除。7例患者采用束流调强质子放射治疗（IMPT）联合束流调强碳离子放射治疗（IMCT）,IMPT放射临床靶区体积（CTV）56 GyE/28次后,采用IMCT给予局部加量治疗15 GyE/5次。1例患者接受了单纯的IMPT治疗。结果 根据新版实体瘤疗效评价标准（RECIST）评估标准,本组5例具有明确肿瘤病灶的患者,在放疗结束时和结束后1个月,3例肿瘤部分缓解（PR）,2例疾病稳定（SD）;4例放疗结束后3个月随访时,有2例达到完全缓解（CR）,1例PR,1例SD。至2016年3月所有患者均无肿瘤进展和死亡。放疗期间,2例发生了3级口腔黏膜反应,随访3个月无重度皮肤反应发生。结论 束流调强粒子放射治疗头颈部腺样囊性癌安全、有效,但后期不良反应和远期疗效尚需更长时间的观察。     

碳离子放射治疗泪囊泪腺肿瘤的剂量学研究

目的 比较碳离子治疗泪囊泪腺肿瘤相对于光子放疗的剂量学差异。方法 利用上海市质子重粒子医院治疗的10例术后残留的泪囊腺肿瘤患者CT图像,重新制定碳离子计划,光子容积调强计划（VMAT）与固定野光子调强计划（IMRT）,所有患者处方均为给予临床靶区54 Gy相对生物学效能（RBE）/18次,并给予临床加量靶区同步加量至63 Gy（RBE）/18次。在计划靶区覆盖相似情况下,比较正常组织受量。结果 在计划靶区覆盖差异无统计学意义的情况下,与光子VMAT和与IMRT相比,碳离子计划患侧与健侧的眼球平均剂量、视神经近似最大剂量（D_2%）与平均剂量均降低（患侧：t=7.35、3.79、4.66、8.48、2.52、2.76,P<0.05;健侧：t=3.87、10.49、9.16、4.43、6.53、5.12,P<0.05）;脑组织平均剂量由（5.65±3.58）和（5.76±2.09）Gy（RBE）降至（0.81±0.90）Gy（RBE）,差异具有统计学意义（t=6.76、17.33,P<0.05）。结论 与光子VMAT与IMRT相比,碳离子计划能有效降低泪囊泪腺肿瘤周围视觉器官受照体积与剂量,具有降低放疗不良反应的潜在优势。     

质子碳离子治疗复发性颅底及颈椎脊索瘤和软骨肉瘤的初步临床结果

目的 探讨采用质子碳离子笔形束扫描技术治疗复发性颅底及颈椎脊索瘤和软骨肉瘤患者的不良反应和近期疗效。方法 收集2014年6月30日至2018年7月30日收治的45例复发性颅底及颈椎肿瘤患者,其中脊索瘤39例,软骨肉瘤6例,中位肿瘤体积57 cm³（6.6~231.7 cm³）。术后复发患者31例,术后放疗后复发14例。行单纯质子治疗1例,质子加碳离子放疗21例,单纯碳离子治疗23例。结果 所有患者均顺利完成治疗。患者中位随访时间29个月（8~57个月）,2年总生存率、局部控制率及无进展生存率分别为82.7%、85.3%及73.8%。除1例3级急性口腔黏膜炎外,未见其他3~4级急性或晚期不良反应。粒子射线放疗作为再程放疗的患者与第1次放疗的患者,其总生存率分别为50.3%和96.2%（χ²=16.969,P<0.05）。结论 质子重离子治疗复发性颅底及颈椎脊索瘤软骨肉瘤取得了较好的短期疗效,长期疗效及不良反应仍需要进一步随访。     

突破肿瘤放射治疗发展瓶颈的重粒子束治疗

重粒子束的高线性能量传递射线突破了常规放射肿瘤的发展瓶颈,是肿瘤放射治疗最尖端技术。重粒子束作为难治性肿瘤治疗的重要手段,取得了令人鼓舞的疗效,尤以碳离子是这一研究领域的亮点。①碳离子是迄今最佳的治疗肿瘤用重粒子射线;②碳离子突出的特点是拥有高相对生物效应值,同时兼有比质子更好的肿瘤剂量适形性的双重优越性;③碳离子放疗对常规放疗抗拒的一些难治性肿瘤疗效好、疗程短,无明显并发症：④碳离子放疗对外科手术困难的肿瘤、邻近重要组织器官的肿瘤仍能够治疗,对老年患者组织器官功能减退及生长发育期的青少年儿童患者具有特殊的临床意义;⑤对常规放疗无效或复发患者的再程放疗仍有效。     

伽玛刀治疗直肠癌术后局部复发53例的临床分析

目的探讨伽玛刀治疗直肠癌术后局部复发的临床意义。方法对2010年1月—2013年1月收治的直肠癌术后局部复发的患者53例采取伽玛刀放疗,50%~70%等剂量曲线覆盖计划靶区,单次周边剂量给予3~5 Gy,周边总剂量控制在35~50 Gy,每周5次,共分割10~11次。放疗第1天开始同步卡培他滨化疗。结果肿瘤控制总有效率CR+PR为90.6%。1年生存率为88.6%(47/53)。疼痛缓解率为94.8%(37/39),便血缓解率为85.7%(6/7),会阴部坠胀感缓解率为85.7%(6/7),里急后重感缓解率为75%(12/16)。无严重的不良反应发生。结论伽玛刀治疗直肠癌术后局部复发,近期疗效满意,能延长患者生存时间,提高患者生存质量。     

质子及重离子治疗肿瘤的现状及研究进展

质子和重离子射线治疗肿瘤,是利用质子和重离子穿过物质形成Bragg峰的物理特性和重离子优越的放射生物学特性,将高剂量区调整嵌合在肿瘤上,同时尽量避开周围正常组织器官。质子及重离子放疗剂量分布优于光子放疗,这有利于提升肿瘤剂量和降低正常组织损伤。近年来,不少研究探索了质子重离子治疗头颈部肿瘤、肺癌、食管癌、肝癌等肿瘤的有效性及安全性,而多个对比光子及质子治疗肿瘤的临床研究也正在进行中。这些研究的结果将有利于更好地了解质子及重离子治疗的特点及优势,以便筛选合适的患者,合理推广质子重离子放疗。     

综合治疗儿童髓母细胞瘤33例临床分析

目的回顾性分析髓母细胞瘤的临床特点,探讨合理治疗方案,分析预后影响因素。方法 2004年8月-2007年12月共收治髓母细胞瘤术后患儿33例。术后3周内开始放疗,先予以全脑全脊髓28~36Gy,再予瘤床处三维适形局部补量至总量50~54Gy,常规分割剂量1.8~2.0Gy/次;为减轻晚反应,部分患儿采用超分割照射技术(1.0Gy/次、2次/d);所有患者在6~8周内完成放疗。全脑全脊髓放疗完成后行1个周期同步化疗,全部放疗结束后再进行序贯化疗3~5个周期;化疗方案为洛莫司汀+长春新碱+顺铂或异环磷酰胺+卡铂+依托泊苷。根据肿瘤是否转移、残存及残存肿瘤大小将患儿分为两组:低风险组(n=24):无转移、肿瘤全切或近全切(残留肿瘤体积≤1.5cm3);高风险组(n=9):已有转移或残留肿瘤体积>1.5cm3。比较两组患者的3年生存率。结果术后残留病灶患儿的放化疗有效率为90.9%(10/11),全组完全缓解(CR)93.9%(31/33),部分缓解(PR)3.0%(1/33),稳定(SD)3.0%(1/33)。所有患者中位生存时间51个月,3年总生存率和无病生存率分别为78.8%、75.8%。高风险和低风险患儿的3年生存率分别为33.3%和95.8%(P<0.01)。不良反应主要为血液系统和消化系统的毒性反应:Ⅲ-Ⅳ度骨髓抑制发生率为21.2%(7/33),恶心发生率87.9%(29/33),伴呕吐者66.7%(22/33)。结论儿童髓母细胞瘤的诊断不难,首选手术治疗,术后联合放化疗的总体疗效好,严重不良反应的发生率较低。肿瘤清除程度是影响预后的因素之一。     

Proton Radiotherapy for Liver Tumors: Dosimetric Advantages Over Photon Plans

The purpose of the study is to dosimetrically investigate the advantages of proton radiotherapy over photon radiotherapy for liver tumors. The proton plan and the photon plan were designed using commercial treatment planning systems. The treatment target dose conformity and heterogeneity and dose-volume analyses of normal structures were compared between proton and photon radiotherapy for 9 patients with liver tumors. Proton radiotherapy delivered a more conformal target dose with slightly less homogeneity when compared with photon radiotherapy. Protons significantly reduced the fractional volume of liver receiving dose greater or equal to 30 Gy (V₃₀) and the mean liver dose. The stomach and duodenal V₄₅ were significantly lower with the use of proton radiotherapy. The V₄₀ and V₅₀ of the heart and the maximum spinal cord dose were also significantly lower with the use of proton radiotherapy. Protons were better able to spare one kidney completely and deliver less dose to one (generally the left) kidney than photons. The mean dose to the total body and most critical structures was significantly decreased using protons when compared to corresponding photon plans. In conclusion, our study suggests the dosimetric benefits of proton radiotherapy over photon radiotherapy. These dosimetric advantages of proton plans may permit further dose escalation with lower risk of complications.     

Bestrahlung von Schädelbasistumoren mit Kohlenstoffionen bei der GSI Erste klinische Ergebnisse und zukünftige Perspektiven

BACKGROUND: Radiobiological and physical examinations suggest clinical advantages of heavy ion irradiation. We report the results of 23 women and 22 men (median age 48 years) with skull base tumors irradiated with carbon ion beams at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, from December 1997 until September 1999. PATIENTS AND METHODS: The study included patients with chordomas (17), chondrosarcomas (10) and other skull base tumors (Table 1). It is the first time that the intensity-controlled rasterscan-technique and the application of positron-emission tomography (PET) for quality assurance was used. All patients had computed tomography for three-dimensional-treatment planning (Figure 1). Patients with chordomas and chondrosarcomas underwent fractionated carbon ion irradiation in 20 consecutive days (median total dose 60 GyE). Other histologies were treated with a carbon ion boost of 15 to 18 GyE delivered to the macroscopic tumor after fractionated stereotactic radiotherapy (median total dose 63 GyE). RESULTS: Mean follow-up was 9 months. Irradiation was well tolerated by all patients. Partial tumor remission was seen in 7 patients (15.5%) (Figure 2). One-year local control rate was 94%. One patient (2.2%) deceased. No severe toxicity and no local recurrence within the treated volume were observed. CONCLUSION: Clinical effectiveness and technical feasibility of this therapy modality could clearly be demonstrated in our study. To evaluate the clinical relevance of the different beam modalities studies with larger patient numbers are necessary. To continue our project a new heavy ion accelerator exclusively for clinical use is planned to be constructed in Heidelberg.     

Carbon Ion Radiotherapy for Chordomas and Low-Grade Chondrosarcomas of the Skull Base

PURPOSE: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas. PATIENTS AND METHODS: Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the "Gesellschaft für Schwerionenforschung" (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction. RESULTS: Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC degrees III have been observed. CONCLUSIONS: These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.     

A case of hepatocellular carcinoma initially treated by carbon ions, followed by protons for marginal recurrence with portal thrombus

We report a case of hepatocellular carcinoma (HCC), initially treated by carbon ions, then subsequently by protons for marginal recurrence. A 52-year-old man with stage II HCC was enrolled in the clinical study for carbon ion therapy. A total dose of 52.5 GyE in 8 fractions was delivered through a right lateral port for 13 days. Dynamic CT performed 7 months after the initiation of carbon ion therapy showed a decrease in the size of the tumor. Dynamic CT performed 12 months after the therapy revealed marginal recurrence of HCC accompanied with portal vein tumor thrombus (PVTT). Proton therapy of 66 GyE in 22 fractions was delivered through posterior and right lateral ports for 33 days. Dynamic CT performed 3 months after the initiation of proton therapy showed a regression of the recurrent tumor and disappearance of the PVTT. No serious adverse effects were observed during or after these two treatments. He was free from further recurrence 27 months after the initiation of the first carbon ion therapy. Both carbon ions and protons were effective with minimal side effects.     

Particle therapy for mucosal melanoma of the head and neck

Purpose

To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT).

Patients and methods

Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33–89 years). Of the total patients, 33 (53?%) had received PT and 29 (47?%) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types.

Results

Median follow-up was 18.0 months (range 5.2–82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93?%/61?% and 93?%/78?% for all patients, 91?%/44?% and 92?%/71?% for the PT patients and 96?%/62?% and 95?%/59?% for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT.

Conclusion

Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity.     

MR imaging of brain injury induced by carbon ion radiotherapy for head and neck tumors.

To clarify the characteristics of magnetic resonance (MR) imaging of radiation-induced brain injury following carbon ion radiotherapy and to observe the changes in lesions over time, we evaluated 40 patients with radiation-induced brain injury from carbon ion radiotherapy for head and neck tumors. Their primary lesions received a radiation dose of 48 to 70.4 Gray equivalent (GyE) in 16 to 18 fractions. MR imaging of radiation-induced brain injury was graded as follows: Grade 1: change in focal white matter; focal contrast enhancement and surrounding edema; Grade 2: nonenhanced area or cystic lesion in enhanced lesion; Grade 3: focal necrosis with mass effect; and Grade 4: mass effect requiring surgical intervention. Radiation-induced brain injury appeared as early as 2 months and as late as 57 months after carbon ion therapy (mean interval, 22.2 months). MR findings of initial lesion were Grade 1 in 26 cases (65.0%), Grade 2 in 13 (32.5%), and Grade 3 in 1 (2.5%). Brain injury was always found in the radiation field initially, but cystic lesion and edema later extended outside the field in 10 cases (25.0%). In follow-up MR studies, size of edema or enhanced lesion was reduced in 17 patients (42.5%) without treatment. Two cases with large cystic lesions required surgery. Improvement of radiation-induced brain injury was observed more often than had been previously described. Because edema and cystic lesion can occasionally extend outside the radiation field, such findings do not exclude the possibility of radiation-induced brain injury. Careful observation is recommended because cystic lesions can enlarge enough to require surgical treatment in some cases.     

Comparative study of dose distribution between carbon ion radiotherapy and photon radiotherapy for head and neck tumor

PURPOSE: A comparative treatment planning study has been performed between carbon ion radiotherapy (CIRT) and photon radiotherapy [three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)] to assess the potential improvements and limitations that could result for locally advanced, nonresectable head and neck tumors. MATERIALS AND METHODS: Seven patients, originally treated with CIRT, were randomly selected for the comparative study. The evaluations analyzed using dose-volume histogram parameters, conformity index, inhomogeneity coefficient, and dose to the organs at risk (OARs). RESULTS: The mean conformity index was 1.46, 1.43, and 1.22 for 3D-CRT, IMRT, and CIRT, respectively. The mean inhomogeneity coefficient was 0.05, 0.07, and 0.02 for 3D-CRT, IMRT, and CIRT respectively. Photon plans resulted in greater volumes of normal tissues at 10% to 95% isodose levels compared with the corresponding carbon ion plans where the volumes increased by a factor of 1.2 to 2.7 for 3D-CRT and 1.2 to 2.0 for IMRT. CONCLUSION: CIRT has the potential to improve the target dose conformity, inhomogeneity coefficient, and OAR sparing when compared with 3D-CRT and IMRT. Compared with 3D-CRT, normal tissue exposure was reduced mainly in the mid-to low-isodose levels using IMRT. Additional improvement was obtained using CIRT.