Skin Toxicity Profile of Photon Radiotherapy versus Proton Beam Therapy in Paediatric and Young Adult Patients with Sarcomas

AimsRadiotherapy is key in the management of patients with both Ewing sarcoma and rhabdomyosarcoma. However, there is little evidence in the literature with regards to radiation-induced skin toxicities (RISTs) for patients treated with conventional radiotherapy with X-rays (XRT) or proton beam therapy (PBT) for these two conditions. In the present study we evaluated acute and late RIST in patients treated within European protocols with either PBT or XRT, taking both clinical and dosimetric variables into consideration.Materials and methodsThis was a retrospective analysis of 79 paediatric/young adult patients treated with radical radiotherapy (with XRT or PBT) and concurrent chemotherapy. In all cases, radiotherapy was given in conventional fractionation (1.8 Gy/fraction). Acute and late RISTs were registered according to the Radiation Therapy Oncology Group (RTOG) scoring system.ResultsWith regards to acute RIST, 47.9% (23/48) of XRT patients and 48.4% (15/31) of PBT patients had acute grade 2/3 toxicity. When it comes to late RIST, 17.5% (7/40 with known toxicity profile) of XRT patients and 29.0% (9/31) of PBT patients had grade 1/2 toxicity. This difference of –11.5% (95% confidence interval –31.2 to 7.9%) in grade 1/2 toxicity between XRT and PBT was not statistically significant (P = 0.25). Regardless of the radiotherapy technique, V30Gy seems a good predictor of acute RIST. Moreover, for the same value of V30Gy, patients who receive PBT may have a higher risk of moderate–severe acute RIST. Perhaps due to the small sample, definitive conclusions on the predictive factors of late RIST could not be drawn.ConclusionsNo clinically meaningful differences in acute and late RIST were observed between PBT and XRT subgroups. Systematic differences in the modelling of the build-up region may exist between XRT and PBT algorithms, which could make the comparison of dose metrics between techniques potentially biased. A more comprehensive analysis of dosimetric data on larger patient cohorts is needed to elucidate the most relevant skin dose metrics. Dose-effect models of RIST for this unique patient population would be an invaluable tool in radiotherapy plan optimisation.     

The Promise of Proton Beam Therapy for Oesophageal Cancer: A Systematic Review of Dosimetric and Clinical Outcomes

AimsDue to its physical advantages over photon radiotherapy, proton beam therapy (PBT) has the potential to improve outcomes from oesophageal cancer. However, for many tumour sites, high-quality evidence supporting PBT use is limited. We carried out a systematic review of published literature of PBT in oesophageal cancer to ascertain potential benefits of this technology and to gauge the current state-of-the-art. We considered if further evaluation of this technology in oesophageal cancer is desirable.Materials and methodsA systematic literature search of Medline, Embase, Cochrane Library and Web of Science using structured search terms was carried out. Inclusion criteria included non-metastatic cancer, full articles and English language studies only. Articles deliberating technical aspects of PBT planning or delivery were excluded to maintain a clinical focus. Studies were divided into two sections: dosimetric and clinical studies; qualitatively synthesised.ResultsIn total, 467 records were screened, with 32 included for final qualitative synthesis. This included two prospective studies with the rest based on retrospective data. There was heterogeneity in treatment protocols, including treatment intent (neoadjuvant or definitive), dose, fractionation and chemotherapy used. Compared with photon radiotherapy, PBT seemed to reduce dose to organs at risk, especially lung and heart, although not for all reported parameters. Toxicity outcomes, including postoperative complications, were reduced compared with photon radiotherapy. Survival outcomes were reported to be at least comparable with photon radiotherapy.ConclusionThere is a paucity of high-quality evidence supporting PBT use in oesophageal cancer. Wide variation in intent and treatment protocols means that the role and ‘gold-standard’ treatment protocol are yet to be defined. Current literature suggests significant benefit in terms of toxicity reduction, especially in the postoperative period, with comparable survival outcomes. PBT in oesophageal cancer holds significant promise for improving patient outcomes but requires robust systematic evaluation in prospective studies.     

Proton beam therapy for locally advanced lung cancer: A review

Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.     

Repurposing Proton Beam Therapy through Novel Insights into Tumour Radioresistance

Despite improvements in radiotherapy, radioresistance remains an important clinical challenge. Radioresistance can be mediated through enhanced DNA damage response mechanisms within the tumour or through selective pressures exerted by the tumour microenvironment (TME). The effects of the TME have in recent times gained increased attention, in part due to the success of immune modulating strategies, but also through improved understanding of the downstream effects of hypoxia and dysregulated wound healing processes on mediating radioresistance. Although we have a better appreciation of these molecular mechanisms, efforts to address them through novel combination approaches have been scarce, owing to limitations of photon therapy and concerns over toxicity. At the same time, proton beam therapy (PBT) represents an advancement in radiotherapy technologies. However, early clinical results have been mixed and the clinical strategies around optimal use and patient selection for PBT remain unclear. Here we highlight the role that PBT can play in addressing radioresistance, through better patient selection, and by providing an improved toxicity profile for integration with novel agents. We will also describe the developments around FLASH PBT. Through close examination of its normal tissue-sparing effects, we will highlight how FLASH PBT can facilitate combination strategies to tackle radioresistance by further improving toxicity profiles and by directly mediating the mechanisms of radioresistance.     

Proton-to-photon comparative treatment planning guidelines for the Australian context

Proton-to-photon comparative treatment planning is a current requirement of Australian Government funding for patients to receive proton beam therapy (PBT) overseas, and a future requirement for Medicare funding of PBT in Australia. Because of the fundamental differences in treatment plan creation and evaluation between PBT and conventional radiation therapy with x-rays (XRT), there is the potential for a lack of consistency in the process of comparing PBT and XRT treatment plans. This may have an impact on patient eligibility assessment for PBT. The objective of these guidelines is to provide a practical reference document for centres performing proton-to-photon comparative planning and thereby facilitate national uniformity.     

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study

AimsProton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT.Materials and methodsChildren younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT.ResultsBetween September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11–23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0–59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3–86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%).ConclusionsOur study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.     

Mathematical Modelling for Patient Selection in Proton Therapy

Proton beam therapy (PBT) is still relatively new in cancer treatment and the clinical evidence base is relatively sparse. Mathematical modelling offers assistance when selecting patients for PBT and predicting the demand for service. Discrete event simulation, normal tissue complication probability, quality-adjusted life-years and Markov Chain models are all mathematical and statistical modelling techniques currently used but none is dominant. As new evidence and outcome data become available from PBT, comprehensive models will emerge that are less dependent on the specific technologies of radiotherapy planning and delivery.     

Management of Ependymoma in Children,Adolescents and Young Adults

Paediatric ependymomas are rare, malignant tumours arising throughout the central nervous system, but most frequently (in children) the posterior fossa. The standard of care for localised disease is gross total resection and focal radiotherapy, resulting in overall survival rates of up to 85%. Despite improvements in survival, treatment remains challenging, with persistently high rates of (rarely curable) relapse alongside risks of significant tumour and treatment-related toxicity. Systemic therapy is currently used to delay radiotherapy in very young children and in the management of metastatic or recurrent disease. Its use in the adjuvant setting is the subject of ongoing studies. Current research efforts are aimed at eliciting a better understanding of molecular biology, correlating this with tumour behaviour and defining targets for potential new agents. Prognosis seems to be related to the extent of surgical resection and the age at presentation. This article reviews clinical aspects of ependymoma management in children and young people.     

Proton beam therapy for hepatocellular carcinoma

Introduction: Radiation therapy is an effective treatment option for hepatocellular carcinoma (HCC) patients. However, radiotherapy for HCC still has limited recognition as a standard treatment option in international consensus guidelines due to a paucity of randomized controlled trials and the risk of hepatotoxicity, which is primarily mediated by baseline liver function and dose delivered to non-tumor liver cells. Proton beam therapy (PBT) may offer advantages over photon-based radiation treatments through its dosimetric characteristic of sparing more liver volume at low to moderate doses. PBT has the potential to reduce radiation-related hepatotoxicity and allow for tumor dose escalation.

Areas covered: This article reviews the clinical rationale for using PBT for HCC patients and clinical outcome and toxicity data from retrospective and prospective studies. PBT-specific technical challenges for these tumors and appropriate selection of patients to be treated with PBT are discussed.

Expert commentary: Local control, overall survival, and toxicity results are promising for liver PBT. Future studies, including ongoing randomized cooperative group trials, will aim to determine the incremental benefit of PBT over photons and which patients are most suitable for PBT.     

Proton beam therapy in rectal cancer: A systematic review and meta-analysis

IntroductionLocally advanced rectal cancer is often treated with neoadjuvant chemoradiotherapy and surgery. Radiotherapy carries significant risk of toxicity to organs at risk (OAR). Proton beam therapy (PBT) has demonstrated to be effective in other cancers, delivering equivalent dosimetric radiation but with the benefit of improved sparing of OAR. This review compares dosimetric irradiation of OAR and oncological outcomes for PBT versus conventional photon-based radiotherapy in locally advanced rectal cancer.MethodsAn electronic literature search was performed for studies with comparative cohorts receiving proton beam therapy and photon-based radiotherapy for rectal cancer.ResultsEight articles with a total of 127 patients met the inclusion criteria. There was significantly less irradiated small bowel with PBT compared to three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) (MD -17.01, CI [-24.06, −9.96], p < 0.00001 and MD -6.96, CI [-12.99, −0.94], p = 0.02, respectively). Similar dosimetric results were observed for bladder and pelvic bone marrow. Three studies reported clinical and oncological results for PBT in recurrent rectal cancer with overall survival reported as 43 %, 68 % and 77.2 %, and one study in primary rectal cancer with 100 % disease free survival.ConclusionPBT treatment plans revealed significantly less irradiation of OAR for rectal cancer compared to conventional photon-based radiotherapy. Trials for recurrent rectal cancer and PBT have shown promising results. There are currently no ongoing clinical trials for primary rectal cancer and PBT. More research is required to validate its potential role in dose escalation, higher complete response rate and organ preservation without increasing toxicity.     

基于EUD鼻咽癌调强放疗中NTCP和TCP的计算程序设计研究

目的 设计一个基于等效均一剂量（EUD）的计算程序来计算鼻咽癌调强放疗（IMRT）计划中正常组织并发症概率（NTCP）和肿瘤控制概率（TCP）。方法 采用具有较强数学特性及友好交互界面等优势的高效编程语言Matlab编写计算NTCP和TCP程序,其中NTCP 数学模型选用基于EUD的Lyman Kutcher Burman模型,而TCP模型则选用Schultheiss逻辑模型 。收集3例接受IMRT治疗的鼻咽癌患者的正常组织和靶区剂量体积直方图（DVH）,计划系统为医科达precise plan。结果编写计算机代码保存为Matlab可执行程序。3例鼻咽癌患者的4种正常组织（脑干、脊髓、左右侧腮腺）和肿瘤的EUD被编写程序算出,进而计算出NTCP和TCP。结论 编写的程序对正常组织耐受量的计算结果与理论值非常吻合,有助于临床选择更安全和高效的治疗方案,将来还可将程序用于其他肿瘤如前列腺癌和肺癌的放疗计划中。     

Individualised Estimation of Quality-adjusted Survival Benefit and Cost-effectiveness of Proton Beam Therapy in Intermediate-stage Hodgkin Lymphoma

AimsRadiotherapy for Hodgkin lymphoma leads to the irradiation of organs at risk (OAR), which may confer excess risks of late effects. Comparative dosimetry studies show that proton beam therapy (PBT) may reduce OAR irradiation compared with photon radiotherapy, but PBT is more expensive and treatment capacity is limited. The purpose of this study is to inform the appropriateness of PBT for intermediate-stage Hodgkin lymphoma (ISHL).Materials and methodsA microsimulation model simulating the course of ISHL, background mortality and late effects was used to estimate comparative quality-adjusted life years (QALYs) lived and healthcare costs after consolidative pencil beam scanning PBT or volumetric modulated arc therapy (VMAT), both in deep-inspiration breath-hold. Outcomes were compared for 606 illustrative patients covering a spectrum of clinical presentations, varying by two age strata (20 and 40 years), both sexes, three smoking statuses (never, former and current) and 61 pairs of OAR radiation doses from a comparative planning study. Both undiscounted and discounted outcomes at 3.5% yearly discount were estimated. The maximum excess cost of PBT that might be considered cost-effective by the UK's National Institute for Health and Care Excellence was calculated.ResultsOAR doses, smoking status and discount rate had large impacts on QALYs gained with PBT. Current smokers benefited the most, averaging 0.605 undiscounted QALYs (range –0.341 to 2.171) and 0.146 discounted QALYs (range –0.067 to 0.686), whereas never smokers benefited the least, averaging 0.074 undiscounted QALYs (range –0.196 to 0.491) and 0.017 discounted QALYs (range –0.030 to 0.086). For the gain in discounted QALYs to be considered cost-effective, PBT would have to cost at most £4812 more than VMAT for current smokers and £645 more for never smokers. This is below preliminary National Health Service cost estimates of PBT over photon radiotherapy.ConclusionIn a UK setting, PBT for ISHL may not be considered cost-effective. However, the degree of unquantifiable uncertainty is substantial.     

CBCT配准前后的肺癌调强放疗计划比较研究

目的 对肺肿瘤利用CBCT图像配准确定PTV外扩距离,与常规调强放疗计划进行比较并行差异评估。方法 选10例肺肿瘤患者每周1次肺部CBCT,每次放疗前后分别进行。对数据依据二参数法得到三维方向外扩距离重新勾画靶区制定计划(校正后),并与原计划(校正前)双肺、脊髓的DVH参数、PTV体积和剂量以及NTCP进行比较,差异行协方差分析或Wilcoxson符号秩检验。结果 经CBCT校正前后计划的PTV最大剂量、最小剂量、平均剂量,双肺V₅、V₁₀、V₂₀、V₃₀、V₅₀均相似(P=0.242~0.663),校正后PTV体积、双肺所受平均剂量有优势(P=0.049、0.035),校正后NTCP随V₅、V₁₀、V₂₀增加有下降趋势(P=0.146、0.053、0.000)。结论 利用CBCT技术校正后可缩小PTV体积,减少双肺平均受量,降低NTCP,有可能提高PTV剂量,从而提高肺癌放疗局部控制率。     

直肠癌IMRT中腹膜腔限量取代肠管限量保护小肠的可行性研究

目的 在直肠癌IMRT过程中,通过比较腹膜腔(PS)和小肠肠管(BL)两种限量条件下的小肠剂量体积和正常组织并发症概率(NTCP),探讨PS限量取代BL限量保护小肠的可行性。方法 选取接受术后辅助放疗的直肠癌患者24例,仰卧和俯卧体位各12例。患者在治疗前和疗程中1~4周各扫描一组CT分别定义为Plan、1周、2周、3周、4周,在每组CT影像上分别勾画PS和BL轮廓。在Plan CT上根据PS、BL两种限量方法分别设计IMRT计划P_PS、P_BL,然后拷贝至1~4周 CT,分别评估每组CT上P_PS、P_BL两种计划的小肠剂量体积和NTCP。结果 24例患者共扫描109套CT影像,设计并拷贝计划218组。PS、BL体积中位数分别为1339.28、250.27 cm³,基于Plan CT两种计划(P_PS、P_BL)的PS和肠管V₁₅中位数分别为918.96、199.57 cm³。基于所有CT影像P_PS计划的小肠剂量体积绝大部分都小于P_BL计划,其中V₁₅为170.07 cm³∶178.58 cm³(P=0.000),两者存在显著相关性(P=0.000)。P_PS计划的慢性、急性不良反应NTCP均明显小于P_BL计划(2.80%∶3.00%,P=0.018;57.32%∶58.64%,P=0.000)。仰卧和俯卧两种体位患者中P_PS计划的绝大部分小肠剂量体积和NTCP都小于P_BL计划,其中V₁₀、V₁₅、V₃₀和急性不良反应NTCP的P值均<0.05。结论 在直肠癌IMRT中将PS限量方法取代BL限量来保护小肠是可行的,可以参考V₁₅<830 cm³作为其剂量限制目标函数。     

How Low Can You Go? The Radiobiology of Hypofractionation

Hypofractionated radical radiotherapy is now an accepted standard of care for tumour sites such as prostate and breast cancer. Much research effort is being directed towards more profoundly hypofractionated (ultrahypofractionated) schedules, with some reaching UK standard of care (e.g. adjuvant breast). Hypofractionation exerts varying influences on each of the major clinical end points of radiotherapy studies: acute toxicity, late toxicity and local control. This review will discuss these effects from the viewpoint of the traditional 5 Rs of radiobiology, before considering non-canonical radiobiological effects that may be relevant to ultrahypofractionated radiotherapy. The principles outlined here may assist the reader in their interpretation of the wealth of clinical data presented in the tumour site-specific articles in this special issue.     

A Dosimetric Comparison of Breast Radiotherapy Techniques to Treat Locoregional Lymph Nodes Including the Internal Mammary Chain

AimsRadiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs).Materials and methodsIn 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance.ResultsOne hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB).ConclusionsSimple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics.     

Uncertainties in model-based outcome predictions for treatment planning

Purpose: Model-based treatment-plan-specific outcome predictions (such as normal tissue complication probability [NTCP] or the relative reduction in salivary function) are typically presented without reference to underlying uncertainties. We provide a method to assess the reliability of treatment-plan-specific dose–volume outcome model predictions.

Methods and Materials: A practical method is proposed for evaluating model prediction based on the original input data together with bootstrap-based estimates of parameter uncertainties. The general framework is applicable to continuous variable predictions (e.g., prediction of long-term salivary function) and dichotomous variable predictions (e.g., tumor control probability [TCP] or NTCP). Using bootstrap resampling, a histogram of the likelihood of alternative parameter values is generated. For a given patient and treatment plan we generate a histogram of alternative model results by computing the model predicted outcome for each parameter set in the bootstrap list. Residual uncertainty (“noise”) is accounted for by adding a random component to the computed outcome values. The residual noise distribution is estimated from the original fit between model predictions and patient data.

Results: The method is demonstrated using a continuous-endpoint model to predict long-term salivary function for head-and-neck cancer patients. Histograms represent the probabilities for the level of posttreatment salivary function based on the input clinical data, the salivary function model, and the three-dimensional dose distribution. For some patients there is significant uncertainty in the prediction of xerostomia, whereas for other patients the predictions are expected to be more reliable. In contrast, TCP and NTCP endpoints are dichotomous, and parameter uncertainties should be folded directly into the estimated probabilities, thereby improving the accuracy of the estimates. Using bootstrap parameter estimates, competing treatment plans can be ranked based on the probability that one plan is superior to another. Thus, reliability of plan ranking could also be assessed.

Conclusions: A comprehensive framework for incorporating uncertainties into treatment-plan-specific outcome predictions is described. Uncertainty histograms for continuous variable endpoint models provide a straightforward method for visual review of the reliability of outcome predictions for each treatment plan.     

T1-2期鼻咽癌RTOG推荐靶区与中国推荐靶区IMRT计划之间后组颅神经NTCP差异性分析

目的 通过研究T_1-2期鼻咽癌IMRT中基于RTOG推荐靶区和中国靶区IMRT计划之间后组颅神经NTCP的差异,为鼻咽癌IMRT中后组颅神经保护提供剂量体积效应依据。方法 选取2013—2015年间T₁、T₂期鼻咽癌病例共20例,分别在其CT定位影像上勾画后组颅神经。根据RTOG0225推荐方法(RTOG靶区方法)和2010年中国鼻咽癌临床分期工作委员会推荐的靶区定义方法(中国靶区方法)勾画靶区和设计治疗计划,计算两种靶区定义方法之间后组颅神经受量及NTCP差异性。结果 RTOG靶区和中国靶区方法的左、右侧后组颅神经受量D_max分别为(7450±273)、(7294±309) cGy和(7361±160)、(7190±395) cGy (左、右侧P=0.018、0.042);D_mean分别为(6735±285) 、(6660±333) cGy和(6446±429) 、(6299±467) cGy (左、右侧P=0.000、0.000);NTCP分别为(60±10)%、(57±13)%和(51±15)%、(45±17)%(左、右侧P=0.000、0.000)。结论 鼻咽癌IMRT中将后组颅神经作为常规OAR来精确勾画并进行剂量评估和NTCP预测是可行的;后组颅神经的NTCP与其靶区接受剂量和受照体积密切相关;中国靶区方法的后组颅神经受量和NTCP都明显小于RTOG靶区方法。     

Dose distribution effects of spot-scanning proton beam therapy equipped with a multi-leaf collimator for pediatric brain tumors

The present study simulated the effect of spot-scanning proton beam therapy (PBT) performed using a device equipped with a multi-leaf collimator (MLC) to calculate the dose distribution. Simulation studies using 18 pediatric patients with brain tumors in the posterior fossa were performed. Treatment plans were created for the MLC at different stages: Fully open (initial plan), fully closed to allow an irradiated area extending to 15 mm from the clinical target volume (CTV) (15-mm plan), or closing only the leaves where an organ at risk (OAR) overlapped with a border at 10 or 5 mm from the CTV (10- and 5-mm plans, respectively). The mean dose values for the brainstem, cervical cord, brain and cochlea in all MLC closure plans decreased as the MLC was closed (P=9.9×10⁻¹⁰, P=1.3×10⁻¹⁷, P=2.1×10⁻¹⁶ and P=2.0×10⁻⁵, respectively). The maximum dose (D_max) values of the cervical cord and cochlea in all MLC closure plans were also decreased as the MLC was closed (P=3.0×10⁻⁴ and P=1.1×10⁻⁵, respectively). The dose to the CTV was almost unchanged. In 10 patients, the D_max of the brain in all MLC-closure plans was higher than that of the initial plan, but the maximum increase was only 0.8 gray relative biological effectiveness [Gy(RBE)]. In conclusion, the existing MLC installed in the treatment device can be used to decrease the OAR dose significantly using spot-scanning PBT without a large capital investment. The dose from the scattered particles was small.