Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit 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 radioresistant 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 efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits 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 concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy 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 eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy 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.

Radical radiotherapy without surgical tumor resection for rectal cancer

In this editorial,I would like to comment on the article,recently published in the World Journal of Clinical Oncology.The article focuses on non-surgical treatments for locally recurrent rectal cancer,including the watch-and-wait(WW)strategy after total neoadjuvant therapy(TNT)and particle beam therapy.As treatment options for rectal cancer continue to evolve,the high complete response rate achieved with TNT has led to the development of a new non-surgical approach:WW.Chemoradiotherapy followed by consolidation chemotherapy,in particular,has a low rate of tumor growth and is a treatment aimed at achieving a cure without surgery.However,the risk of recurrence within two years is significant,necessitating careful follow-up.Establishing standardized follow-up methods that can be implemented by many physicians is essential.Carbon ion radiotherapy has demonstrated high local control with a low incidence of severe late toxicities,even after previous pelvic radiotherapy.While these new non-surgical curative treatments for rectal cancer require further investigation,future advancements in this field are anticipated.

Carbon ion radiotherapy for bladder cancer: A case report

BACKGROUND Radical cystectomy is considered the first choice for the treatment of muscleinvasive bladder cancer.However,for some patients who have lost the indications for surgery,external beam radiotherapy is a non-invasive and effective treatment.CASE SUMMARY A 76-year-old patient with bladder cancer who had serious comorbidities and could not tolerate surgery or chemotherapy came to the Wuwei Heavy Ion Center.He received carbon ion radiotherapy(CIRT)with a whole-bladder dose of 44 GyE and tumor boost of 20 GyE.When he finished CIRT,his bladder cancer-related hematuria completely disappeared,and computed tomography examination showed that the tumor had obviously decreased in size.At the 3-mo follow-up,the tumor disappeared,and there were no acute or late adverse events.CIRT was well tolerated in this patient.CONCLUSION CIRT may allow for avoiding resection and was well tolerated with curative outcomes.

Evaluation of Patient-Specific Quality Assurance for Carbon Ion Radiotherapy Using Full Energy Scanning Method at QST Hospital

Purpose: Patient-specific QA (PSQA) measurements for carbon ion radiotherapy (CIRT) are critical components of processes designed to identify discrepancies between calculated and delivered doses. We report the results of PSQA conducted at the QST Hospital during the period from September 2017 to March 2018. Methods: We analyzed PSQA results for 1448 fields for 10 disease sites with various target volumes, target depths and number of energy layers. For the PSQA, all the planned beams were recalculated on a water phantom with treatment planning software. The recalculated dose distributions were compared with the measured distributions using a 2D ionization chamber array at three depths, including 95% of the area of the prescription dose. These recalculated dose distributions were evaluated using the 3%/3mm gamma index with a passing threshold of 90%. Results: The passing rates for prostate, head and neck, and bone and soft tissue were 96.8%, 99.3%, and 91.7%, respectively. Additionally, 94.7% of lung plans with low energy beams passed. Overall, the CIRT in the QST Hospital reached a high passing rate of more than 95%. Although the remaining 5% failed to pass, there was no dependence between measurement depth and disease sites in these failures. Conclusion: Using PSQA measurements, we confirmed consistency between the planned and delivered doses for CIRT using the full energy scanning method.

Hypofractionated particle beam therapy for hepatocellular carcinoma–a brief review of clinical effectiveness

Hepatocellular carcinoma(HCC)is the fifth most common malignancy and the second leading cause of cancer mortality worldwide.The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment.Although radiotherapy has not been considered a preferred treatment modality for HCC,charged particle therapy(CPT),including proton beam therapy(PBT)and carbon ion radiotherapy(CIRT),possesses advantages(for example,it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation)and has emerged as an alternative treatment option for HCC.With the technological advancements in CPT,various radiation dosages of CPT have been used for HCC treatment via CPT.However,the efficacy and safety of the evolving dosages remain uncertain.To assess the association between locoregional control of HCC and the dose and regimen of CPT,we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes.Overall,CPT provides a better local control rate compared with photon beam therapy,ranging from 80%to 96%,and a 3-year overall survival ranging from 50%to 75%,and it results in rare grade 3 toxicities of the late gastrointestinal tract(including radiation-induced liver disease).Regarding CPT for the treatment of locoregional HCC,conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract.In contrast,the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

Carbon ion radiotherapy boost in the treatment of glioblastoma:a randomized phase Ⅰ/Ⅲ clinical trial

Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. Methods and design: Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradia-tion with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assess-ment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. Discussion: The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malig-nancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio-resistance. The unique physical and biological properties of CIRT are expected to overcome these microenviron-mental limitations to confer an improved tumor-killing ability and anti-tumor immune response, which could result in an improvement in OS with minimal toxicity. Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR-OID-17013702.

Results of Carbon Ion Radiotherapy for Skin Carcinomas in 33 Patients

Purpose: To evaluate outcome and toxicity after carbon ion radiotherapy (RT) in skin carcinomas. Patients and Methods: Between November 2006 to September 2008,

碳离子放射治疗1例多结节型肝细胞癌

肝细胞癌(hepatocellular carcinoma HCC)发病率高,在发现时只有不到1/3的患者适合手术治疗,随着临床经验的积累,放射治疗已成为不可切除肝癌的优选方法。我们报道了一例多结节型肝细胞癌患者接受碳离子放疗并取得了良好疗效的病例。一例53岁女性在体检时发现肝内多发结节(约14个),经穿刺病检提示中分化肝细胞癌,被转诊至武威重离子中心进行碳离子治疗,剂量为66 Gy(RBE)/10 f,4个月时随诊复查疗效良好。

A preliminary study on effect of carbon ion radiotherapy on bone marrow suppression

Objective:To explore the effect of carbon ion radiotherapy(CIRT)on the bone marrow adjacent to or within the treatment fields,and to observe the bone marrow toxicities after CIRT alone.Methods:Twenty-one patients with malignant tumors of different body parts and treated with CIRT in Heavy Ion Center,Wuwei Cancer Hospital were analyzed retrospectively.The data of white blood cells,neutrophils,hemoglobin,platelets,lymphocytes and globulin before treatment,7,14 and 28 d during treatment,and 1 and 3 months after treatment were collected.Hematological toxicities were measured according to the Common Terminology Criteria for Adverse Events(CTCAE,Version 4.03)criteria.Dose-volume histogram parameters were obtained for all patients and analyzed for their correlation with myelosuppression.Univariate analysis was performed for patients’sex,age group,tumor site,radiation dose,and Karnofsky performance score(KPS)was used as an independent factor to find predictors factors for the risk of myelosuppression.Results:CIRT minimized the dose radiated to the bone marrow.Overall,volume receiving 3 GyE(V3)or more of the bone marrow were less than 0.5%,especially V5 less than 0.1%.No patients treated with carbon ion radiotherapy developed grade III or IV myelosuppression.Seven patients(33.3%)developed grade I myelosuppression and one patient(4.8%)developed grade II myelosuppression,and most of them showed reduced white blood cell counts.There were no significant differences in hemoglobin and globulin levels before and after CIRT.Univariate analysis did not find any statistically significant predictors for myelosuppression.Conclusions:CIRT is effective in preserving bone marrow function regardless of tumor site.Patients receiving CIRT alone have a low incidence of grade III myelosuppression and a mild effect on globulins.There was no significant correlation between occurrence of myelosuppression and the dose and site irradiated by CIRT.

C离子束放射治疗肿瘤的进展

重离子(C离子)用于肿瘤放射治疗具有物理学和生物学两方面的优势,被誉为面向21世纪最佳放疗用射线。综合论述了世界各国重离子束治癌的发展历史,在日本国立放射医学综合研究所(NIRS)提供的临床试验数据基础上分析了C离子束治疗的适应症以及对正常组织的放射损伤。此外,通过分析潜在患者人数和治疗相关硬件与软件设备,对C离子束治癌的运用前景做了初步评估。

碳离子束与X射线对女性恶性肿瘤患者外周血淋巴细胞亚群的影响

分析女性乳腺癌及宫颈癌患者外周血在接受不同剂量碳离子束与X射线辐射前后淋巴细胞亚群数值的变化。抽取5例宫颈癌、5例女性乳腺癌患者的外周静脉血,经照射后(设未接受辐射组、1、2 GyE碳离子束组、及1、2 Gy的X射线组)进行淋巴细胞亚群检测。采用独立样本t检验,分别对两组离体血样本进行CD3^+、CD8^+、CD4^+、NK细胞、B细胞、CD4^+/CD8^+两两组间对比,分析数值变化情况。结果显示:两组离体血在接受不同射线、不同剂量照射后,淋巴细胞亚群检测结果差异无显著性的意义(p>0.05);接受高线性传能密度(Linear energy transfer,LET)碳离子照射时,乳腺癌组中CD4^+值随剂量增加而升高,宫颈癌组数值则表现出相反的趋势;接受6 MV-X射线照射时,宫颈癌组中NK细胞数值随剂量增加而下降,而乳腺癌组则相反;接受碳离子束照射时,两病种受到1 GyE照射后NK细胞数值均较未照射组数值升高,2 GyE则均较未照射组数值下降。结果提示:女性生殖系统最常见两种恶性肿瘤离体外周血对高LET碳离子和低LET的6 MV-X射线照射表现出了不同的免疫应答反应。

重离子束(^(12)C^(6+))治疗头颈部浅表肿瘤疗效观察

目的:观察采用重离子研究装置(HIRFL)引出重离子束治疗头颈部浅表肿瘤的近期疗效和急性不良反应。方法:自2007年1月至2010年10月,我院13例头颈部浅表肿瘤患者采用能量为80MeV/u～100MeV/u的碳离子(^(12)^(6+))束进行重离子束放射治疗。总剂量46GyE～70GyE,1次/天,连续12天。应用RTOG急性放射损伤分级标准判断不良反应,应用WHO疗效标准评价近期疗效。结果:非恶黑性皮肤癌、乳头状瘤、恶性黑色素瘤有效率(CR+PR)分别为100%(9/9)、50%(1/2)和50%(1/2),13例患者总局部控制率为85%(11/13)。皮肤不良反应发生率1、2、3度分别为30.8%(4/13),15.4%(2/13),15.4%(2/13),未观察到4级皮肤不良反应。结论:重离子束放射治疗头颈部浅表肿瘤有较好的近期疗效,不良反应轻微,患者可耐受。

质子/碳离子治疗系统注册申报技术资料审评关注点

该文主要介绍了质子/碳离子治疗系统申报注册时,技术审评关注的几点内容,供制造商在申报注册时参考。

PET在肿瘤诊断和重离子治疗方面的应用(一)

分子影像是一门近几年发展起来的新的学科领域,它使疾病在分子、基因水平上的早期诊断和监测以及进一步地评价疗效成为可能,正电子断层显像(PET)就是分子影像发展的一个代表。本文简要介绍了PET在肿瘤诊断方面的应用,同时对重离子治疗及PET在重离子治疗疗效监测方面的应用作了简要说明。

PET在肿瘤诊断和重离子治疗方面的应用(二)

分子影像是一门近几年发展起来的新的学科领域,它使疾病在分子、基因水平上的早期诊断和监测以及进一步地评价疗效成为可能,正电子断层显像(PET)就是分子影像发展的一个代表。本文简要介绍了PET在肿瘤诊断方面的应用,同时对重离子治疗及PET在重离子治疗疗效监测方面的应用作了简要说明。

碳离子束放射治疗肿瘤的临床进展

带电粒子放疗通常被认为是肿瘤放射治疗的前沿技术。而碳离子束放射治疗(C-ion RT)在近年来带电粒子治疗肿瘤中应用日趋广泛且治疗效果明显。世界范围内有几十家质子治疗中心,主要分布在美国、欧洲和亚洲,但使用C-ion RT肿瘤的只有日本、德国、中国等几个国家。自1994年以来,日本一直在用碳离子束治疗癌症,且目前已有5个碳离子中心在收治患者,尚有数个中心正在建设中。总结这年来碳离子在临床应用的经验、碳离子高效低毒的治疗效果及在治疗难治性肿瘤和抗放射线肿瘤方面的优异特性,可进一步了解肿瘤放射治疗的前沿进展,以指导新的重离子治疗中心的设计和建设。

碳离子辐射诱导的远隔效应

放射治疗诱导的远隔效应能够抑制非辐射区域内肿瘤的生长,目前已有临床和临床前研究表明,常规放疗射线(X射线、γ射线)能够诱导远隔效应的发生,但是对于其发生的机理以及碳离子诱导的远隔效应研究较少。与常规放疗射线相比,碳离子束具有高传能线密度、高相对生物效应、低氧增强比以及复杂DNA损伤等优势,并且具有激活肿瘤细胞更强免疫原性的潜力。本文综述了常规放疗以及碳离子放射治疗诱导的远隔效应及其机理,为寻找更有效的癌症放疗方法提供参考。

碳离子束放射治疗肿瘤的临床进展

带电粒子治疗肿瘤通常被认为是肿瘤放射治疗的前沿技术,目前在临床广泛用于肿瘤治疗的主要是质子和碳离子。世界范围内现已建成运行的质子治疗中心较多,但是碳离子束放疗中心较少,截至目前,只有日本、德国、中国、意大利、奥地利等少数几个国家应用于临床,曰本自1994年以来一直在用碳离子束治疗癌症,且目前曰本国内已有6个碳离子中心在运营收治病人,尚有数个中心正在建设中3到2018年底为止,世界范围内超过24905名患者接受了碳离子治疗,190036名患者接受了质子治疗。总结这20几年来碳离子在临床应用的经验可以使我们进一步了解肿瘤放射治疗前沿进展,并帮助指导关于新的重离子治疗中心的设计和建设的战略决策。

腺样囊性癌的碳离子治疗

腺样囊性癌(adenoid cystic carcinoma,ACC)发病率较低,常见于头颈部唾液腺恶性肿瘤中,可手术的患者手术治疗加术后放疗效果尚可,对于无法手术的患者单纯光子线放疗效果不理想。碳离子具有优于常规光子线的放射物理学和生物学特性,有利于对肿瘤的控制和正常组织的保护。目前全世界范围内可以开展碳离子治疗的单位不多,主要集中在德国、日本、美国以及中国上海,治疗的方式主要包括碳离子单独应用治疗ACC、碳离子与调强放射治疗(IMRT)联合治疗ACC、碳离子治疗复发的ACC、碳离子治疗年幼的ACC患者以及正在研究的碳离子放疗与靶向药物及化疗的联合,此类研究可以证实碳离子在临床应用的有效性及安全性。