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Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy 接受质子束治疗的有利风险前列腺癌患者的长期临床结果
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-10-20 DOI: 10.14338/IJPT-21-00016
A. Bao, A. Barsky, R. Maxwell, J. Bekelman, S. Both, J. Christodouleas, C. Deville, P. Fang, Z. Tochner, N. Vapiwala
Purpose Long-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment. Methods One hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS. Results The median length of follow-up was 8.3 years (range, 1.2–10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05). Conclusion Disease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies.
目的:关于质子束治疗(PBT)对风险良好的完整前列腺癌(PC)患者的疾病控制结果的长期数据有限。在此,我们报告了本院以PBT为主要治疗的PC患者的长期疾病控制结果。方法对我院2010 ~ 2012年接受前列腺明确PBT治疗的166例有利风险PC患者进行回顾性分析。研究结果包括生化无失败生存期(BFFS)、生化失败、局部失败、区域失败、远端失败、pc特异性生存期和总生存期。对失效模式也进行了分析。采用多变量Cox比例风险模型估计闺蜜关系的独立预测因子。结果中位随访时间8.3年(1.2 ~ 10.5年)。大多数患者为低风险疾病(58%,n = 96),治疗开始时的中位年龄为64岁。166例男性患者中,生化失败13例(7.8%),局部失败8例(4.8%),局部失败2例(1.2%)。1例患者闭孔淋巴结局部衰竭,另1例患者髂外淋巴结局部衰竭。没有患者出现远端衰竭。死亡5例(3.0%),均非PC所致。5年和8年的好朋友率分别为97%和92%。在多变量Cox比例风险模型中,没有临床疾病特征或治疗相关因素与BFFS相关(均P < 0.05)。结论我们对PBT的评估报告的疾病控制率与先前临床局部完整PC分析报告的疾病控制率相似,这些分析使用调强放疗,三维适形放疗或根治性前列腺切除术作为最终治疗。此外,与之前的PBT研究相比,最好朋友的比率即使没有提高,也是相似的。
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引用次数: 2
Pericardial Effusion during Proton Therapy in a Patient with Chemorefractory Hodgkin Lymphoma. 化疗难治性霍奇金淋巴瘤患者质子治疗期间心包积液
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-10-18 eCollection Date: 2022-01-01 DOI: 10.14338/IJPT-21-00010
Ashley Way, Savas Ozdemir, Barbara Berges, Nataliya Getman, Xiaoying Liang, Nancy P Mendenhall, Graham Collins, David Cutter, Raymond B Mailhot Vega

We present a case of recurrent pericardial effusion presenting during proton therapy in a 24-year-old female receiving mediastinal treatment for classical Hodgkin lymphoma. Pericardial effusion is typically considered an event accompanying lymphoma diagnosis or as a subacute or late effect of radiotherapy. Rarely has it been described as occurring during radiation treatment with photon-based radiotherapy, let alone proton therapy. It is unclear what underlying cause triggered recurrent effusion in this patient. Identifying and managing pericardial effusion during treatment delivery is important to consider as it may affect radiation dosimetry, particularly with proton therapy. Doing so will help ensure patients receive optimal treatment and minimize the risks of morbidity and mortality.

我们报告一例24岁女性在质子治疗期间复发性心包积液,该女性接受纵隔治疗,治疗经典霍奇金淋巴瘤。心包积液通常被认为是伴随淋巴瘤诊断的事件,或是放疗的亚急性或晚期影响。很少有人描述它发生在光子放射治疗的放射治疗过程中,更不用说质子治疗了。目前尚不清楚是什么根本原因导致该患者反复出现积液。在治疗过程中识别和管理心包积液很重要,因为它可能会影响辐射剂量测定,尤其是质子治疗。这样做将有助于确保患者得到最佳治疗,并将发病率和死亡率风险降至最低。
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引用次数: 0
Proton Therapy of Prostate and Pelvic Lymph Nodes for High Risk Prostate Cancer: Acute Toxicity. 前列腺和盆腔淋巴结质子治疗高危前列腺癌:急性毒性。
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-09-14 eCollection Date: 2021-01-01 DOI: 10.14338/IJPT-20-00094.1
Richard Choo, David W Hillman, Thomas Daniels, Carlos Vargas, Jean Claude Rwigema, Kimberly Corbin, Sameer Keole, Sujay Vora, Kenneth Merrell, Bradley Stish, Thomas Pisansky, Brian Davis, Adam Amundson, William Wong

Purpose: To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate cancer.

Materials and methods: A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data.

Results: Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (P = 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy.

Conclusion: A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.

目的:评估靶向前列腺/精囊和盆腔淋巴结的强度调节质子治疗(IMPT)对前列腺癌的急性胃肠道(GI)和泌尿生殖系统(GU)毒性。材料和方法:一项前瞻性研究(ClinicalTrials.gov: NCT02874014),评估中度低分割IMPT治疗高风险或不利的中危前列腺癌,累积了56例患者的目标样本量。前列腺/精囊和盆腔淋巴结分别以6750和4500厘米放射生物学当量(cGyRBE)同时治疗,每25天一次。所有患者均接受雄激素剥夺治疗。根据不良事件通用术语标准(版本4)的7个GI和9个GU类别,在基线、放射治疗期间每周和放射治疗后3个月对急性GI和GU毒性进行前瞻性评估。分类数据的比较采用Fisher精确检验。结果:中位年龄为75岁。中位随访时间为25个月。55例患者可进行急性毒性评估。分别有62%和2%的患者出现急性1级和2级胃肠道毒性。2级胃肠道毒性为直肠炎。分别有65%和35%的患者有急性1级和2级GU毒性。3种最常见的2级GU毒性是尿频、尿急和梗阻症状。没有急性GI或GU毒性≥3级。基线GI和GU症状的存在分别与更大的急性GI和GU毒性相关。在45例有基线GU症状的患者中,44%发生急性2级GU毒性,而在10例无基线GU症状的患者中只有10% (P = 0.07)。虽然急性1级和2级GI和GU毒性在放疗期间很常见,但大多数在放疗后3个月消退。结论:针对前列腺/精囊和区域盆腔淋巴结的中度低分割IMPT耐受性良好,无急性≥3级GI或GU毒性。有基线GU症状的患者有较高的急性2级GU毒性发生率。
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引用次数: 3
Comparisons of 3-Dimensional Conformal and Intensity-Modulated Neutron Therapy for Head and Neck Cancers. 头颈部癌症的三维适形疗法与强度调制中子疗法的比较
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-09-14 eCollection Date: 2021-01-01 DOI: 10.14338/IJPT-20-00059.1
Natalie Viscariello, Matthew D Greer, Upendra Parvathaneni, Jay J Liao, George E Laramore, Robert D Stewart

Purpose: Neutron therapy is a high linear energy transfer modality that is useful for the treatment of radioresistant head and neck (H&N) cancers. It has been limited to 3-dimensioanal conformal-based fast-neutron therapy (3DCNT), but recent technical advances have enabled the clinical implementation of intensity-modulated neutron therapy (IMNT). This study evaluated the comparative dosimetry of IMNT and 3DCNT plans for the treatment of H&N cancers.

Materials and methods: Seven H&N IMNT plans were retrospectively created for patients previously treated with 3DCNT at the University of Washington (Seattle). A custom RayStation model with neutron-specific scattering kernels was used for inverse planning. Organ-at-risk (OAR) objectives from the original 3DCNT plan were initially used and were then systematically reduced to investigate the feasibility of improving a therapeutic ratio, defined as the ratio of the mean tumor to OAR dose. The IMNT and 3DCNT plan quality was evaluated using the therapeutic ratio, isodose contours, and dose volume histograms.

Results: When compared with the 3DCNT plans, IMNT reduces the OAR dose for the equivalent tumor coverage. Moreover, IMNT is most advantageous for OARs in close spatial proximity to the target. For the 7 patients with H&N cancers examined, the therapeutic ratio for IMNT increased by an average of 56% when compared with the 3DCNT. The maximum OAR dose was reduced by an average of 20.5% and 20.7% for the spinal cord and temporal lobe, respectively. The mean dose to the larynx decreased by an average of 80%.

Conclusion: The IMNT significantly decreases the OAR doses compared with 3DCNT and provides comparable tumor coverage. Improvements in the therapeutic ratio with IMNT are especially significant for dose-limiting OARs near tumor targets. Moreover, IMNT provides superior sparing of healthy tissues and creates significant new opportunities to improve the care of patients with H&N cancers treated with neutron therapy.

目的:中子疗法是一种高线性能量转移模式,可用于治疗放射性耐药的头颈部(H&N)癌症。它一直局限于基于3-dimensioanal适形的快速中子治疗(3DCNT),但最近的技术进步使强度调制中子治疗(IMNT)得以临床应用。本研究评估了用于治疗 H&N 癌症的 IMNT 和 3DCNT 方案的剂量测定比较:在华盛顿大学(西雅图)为之前接受过 3DCNT 治疗的患者回顾性地创建了七个 H&N IMNT 计划。反规划使用了带有中子特异性散射核的定制 RayStation 模型。最初使用原始 3DCNT 计划中的濒危器官(OAR)目标,然后有计划地减少目标,以研究提高治疗比的可行性,治疗比定义为平均肿瘤剂量与濒危器官剂量之比。使用治疗比、等剂量等值线和剂量体积直方图对 IMNT 和 3DCNT 计划的质量进行了评估:结果:与 3DCNT 计划相比,在同等肿瘤覆盖范围内,IMNT 减少了 OAR 剂量。此外,IMNT 对空间上接近靶点的 OAR 最具优势。在接受检查的 7 名 H&N 癌症患者中,与 3DCNT 相比,IMNT 的治疗率平均提高了 56%。脊髓和颞叶的最大OAR剂量分别平均减少了20.5%和20.7%。喉部的平均剂量平均减少了 80%:结论:与3DCNT相比,IMNT能明显降低OAR剂量,并提供相当的肿瘤覆盖率。IMNT 对肿瘤靶点附近的剂量限制性 OAR 的治疗率的改善尤为显著。此外,IMNT 还能更好地保护健康组织,为改善接受中子治疗的 H&N 癌症患者的护理创造了重要的新机会。
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引用次数: 0
Biologically Effective Dose and Rectal Bleeding in Definitive Proton Therapy for Prostate Cancer 癌症质子治疗中的生物学有效剂量和直肠出血
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-09-08 DOI: 10.14338/IJPT-21-00007.1
R. Bhangoo, M. Petersen, G. F. Bulman, C. Vargas, C. Thorpe, Jason Shen, W. Wong, J. Rwigema, T. Daniels, S. Keole, S. Schild, Y. Rong, T. DeWees
Purpose and Objectives With increasing use of hypofractionation and extreme hypofractionation for prostate cancer, rectal dose-volume histogram (DVH) parameters that apply across dose fractionations may be helpful for treatment planning in clinical practice. We present an exploratory analysis of biologically effective rectal dose (BED) and equivalent rectal dose in 2 Gy fractions (EQD2) for rectal bleeding in patients treated with proton therapy across dose fractionations. Materials and Methods From 2016 to 2018, 243 patients with prostate cancer were treated with definitive proton therapy. Rectal DVH parameters were obtained from treatment plans, and rectal bleeding events were recorded. The BED and EQD2 transformations were applied to each rectal DVH parameter. Univariate analysis using logistic regression was used to determine DVH parameters that were significant predictors of grade ≥ 2 rectal bleeding. Youden index was used to determine optimum cutoffs for clinically meaningful DVH constraints. Stepwise model-selection criteria were then applied to fit a “best” multivariate logistic model for predicting Common Terminology Criteria for Adverse Events grade ≥ 2 rectal bleeding. Results Conventional fractionation, hypofractionation, and extreme hypofractionation were prescribed to 117 (48%), 84 (34%), and 42 (17.3%) patients, respectively. With a median follow-up of 20 (2.5-40) months, 10 (4.1%) patients experienced rectal bleeding. On univariate analysis, multiple rectal DVH parameters were significantly associated with rectal bleeding across BED, EQD2, and nominal doses. The BED volume receiving 55 Gy > 13.91% was found to be statistically and clinically significant. The BED volume receiving 55 Gy remained statistically significant for an association with rectal bleeding in the multivariate model (odds ratio, 9.81; 95% confidence interval, 2.4-40.5; P = .002). Conclusion In patients undergoing definitive proton therapy for prostate cancer, dose to the rectum and volume of the rectum receiving the dose were significantly associated with rectal bleeding across conventional fractionation, hypofractionation, and extreme hypofractionation when using BED and EQD2 transformations.
目的和目的随着癌症低分级和极低分级的使用越来越多,适用于剂量分级的直肠剂量-体积直方图(DVH)参数可能有助于临床实践中的治疗计划。我们对质子治疗患者直肠出血的生物学有效直肠剂量(BED)和2 Gy组分的等效直肠剂量(EQD2)进行了探索性分析。材料与方法2016年至2018年,对243例癌症前列腺癌患者进行了明确的质子治疗。从治疗计划中获得直肠DVH参数,并记录直肠出血事件。将BED和EQD2变换应用于每个直肠DVH参数。使用逻辑回归的单变量分析用于确定DVH参数,这些参数是≥ 2例直肠出血。Youden指数用于确定具有临床意义的DVH限制的最佳临界值。然后应用逐步模型选择标准来拟合“最佳”多变量逻辑模型,用于预测不良事件等级≥ 2例直肠出血。结果常规分级、低分级和极低分级分别为117例(48%)、84例(34%)和42例(17.3%)。中位随访时间为20(2.5-40)个月,10名(4.1%)患者出现直肠出血。在单变量分析中,多个直肠DVH参数与BED、EQD2和标称剂量的直肠出血显著相关。接收55Gy的BED体积 > 13.91%具有统计学和临床意义。在多变量模型中,接受55Gy治疗的BED容量与直肠出血的相关性仍然具有统计学意义(优势比,9.81;95%置信区间,2.4-40.5;P = .002)。结论在接受前列腺癌症明确质子治疗的患者中,当使用BED和EQD2转化时,通过常规分级、低分级和极低分级,直肠剂量和接受剂量的直肠体积与直肠出血显著相关。
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引用次数: 0
Nuclear Fragmentation Imaging for Carbon-Ion Radiation Therapy Monitoring: an In Silico Study 核碎片成像用于碳离子放射治疗监测:一项计算机研究
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-09-01 DOI: 10.14338/ijpt-20-00040.1
A. Bey, Jiasen Ma, K. Furutani, M. Herman, Jedediah E. Johnson, R. Foote, C. Beltran
Purpose This article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings. Materials and Methods A proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers. Results The IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u. Conclusions This work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.
目的本文提出了一种基于辐照组织中碳离子核碎裂的体内成像技术,用于临床环境中碳离子放射治疗(CIRT)治疗交付和质量保证的潜在实时监测。材料和方法设计了一个概念验证成像和监测系统(IMS)来实现这项技术。对一个预期的铅笔束扫描CIRT喷嘴进行了蒙特卡罗模拟。开发IMS基准考虑了位于目标体模和列表模式数据采集下游的5×5-cm2像素化带电粒子探测器堆栈。研究了检测到的碎片的丰度和产生来源,即顶点。碎片轨迹由直线近似,并建立了波束反向投影算法来重建顶点。然后使用顶点的空间分布来确定与平面图相关的标记。结果IMS技术应用于原发性脑肿瘤模拟CIRT病例。最终恢复了四个治疗计划监测标志物:深度剂量分布相关曲线、离子束范围、治疗目标边界和束点位置。在150和290MeV/u之间的典型治疗能量下,获得了有希望的毫米级(3mm,≤10%不确定度)光束范围和亚毫米级(位移<3cm时精度≤0.6mm)光束点位置验证精度。结论这项工作证明了一种可行的CIRT治疗交付在线监测技术。该方法的强大优势在于,它只需要很少的信号输入(位置和定时),可以用现成的技术同时获取。未来的研究将探讨该技术在运动敏感器官部位和患者组织异质性方面的适用性。使用候选探测器采集系统的波束内测量对于验证IMS基准性能和随后在临床中的部署至关重要。
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引用次数: 1
Demonstration of the FLASH Effect Within the Spread-out Bragg Peak After Abdominal Irradiation of Mice 小鼠腹部辐照后展开布拉格峰内FLASH效应的论证
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-08-19 DOI: 10.14338/IJPT-20-00095
T. Evans, J. Cooley, M. Wagner, Tianning Yu, T. Zwart
Purpose The effects of FLASH-level dose rates delivered at the spread-out Bragg peak (SOBP) on normal tissue damage in mice were investigated. Materials and Methods Fifty nontumor-bearing mice received abdominal irradiation, 30 at FLASH dose rates (100 Gy/s) and 20 at conventional dose rates (0.1 Gy/s). Total dose values ranged from 10 to 19 Gy, delivered in a single spot by a synchrocyclotron proton therapy system. Centered on the abdomen, the collimated field delivered was an 11-mm diameter circle with a water-equivalent depth of 2.4 cm from entrance to distal 80% dose. A ridge filter was used to provide dose uniformity over the full 2.4-cm range. The spatial distribution was identical for both the FLASH and conventional deliveries. Results Overall survival and individual mouse weights were tracked for 21 days after the exposure date, and LD50 values were compared for the FLASH and conventional dose rate groups. Mice exposed to FLASH dose rates had a higher LD50 value as compared with mice exposed to conventional dose rates, with a dose-dependent improvement in survivability of 10% to 20%. The FLASH cohort also showed greater or equal percent population survival for each day of the study. Conclusion These results are preliminary confirmation of the potential for the combination of the advantages of the Bragg peak with the normal tissue sparing benefits of FLASH treatments. This experiment also confirms that pulsed synchrocyclotrons can be used for the purpose of FLASH research and treatment.
目的研究扩展Bragg峰(SOBP)下的flash水平剂量率对小鼠正常组织损伤的影响。材料与方法50只非荷瘤小鼠腹腔照射,30只采用FLASH剂量率(100 Gy/s), 20只采用常规剂量率(0.1 Gy/s)。总剂量值范围从10到19戈瑞,由同步回旋加速器质子治疗系统在一个点交付。以腹部为中心,准直视场为直径11 mm的圆形,从入口到远端80%剂量的水当量深度为2.4 cm。脊状过滤器用于在整个2.4 cm范围内提供剂量均匀性。快闪和常规分娩的空间分布相同。结果追踪暴露后21天的总存活率和个体体重,并比较FLASH和常规剂量率组的LD50值。与暴露于常规剂量率的小鼠相比,暴露于FLASH剂量率的小鼠具有更高的LD50值,其生存能力的剂量依赖性改善为10%至20%。FLASH队列也显示,研究中每天的人口存活率更高或相等。结论这些结果初步证实了将Bragg峰的优势与FLASH治疗的正常组织保留优势结合起来的潜力。本实验也证实了脉冲同步回旋加速器可以用于FLASH的研究和治疗。
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引用次数: 12
The Advantage of Proton Therapy in Hypothalamic-Pituitary Axis and Hippocampus Avoidance for Children with Medulloblastoma. 小儿髓母细胞瘤质子治疗下丘脑-垂体轴及海马回避的优势。
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-08-02 eCollection Date: 2022-01-01 DOI: 10.14338/IJPT-21-00001.1
Saif Aljabab, Shushan Rana, Shadonna Maes, Avril O'Ryan-Blair, Jackie Castro, Jack Zheng, Lia M Halasz, Phillip J Taddei

Purpose: Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI.

Materials and methods: We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D95) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (Dmean ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance.

Results: Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; P < .001) and hippocampi (39.8 versus 22.8 Gy; P < .001). The composite HPA Dmean was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans (P = .05). Hippocampi composite Dmean was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans (P = .02). The IMPT CTV D95 coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans (P < .001) The spared mean volume was only 1.35% (19.8 cm3) of the whole-brain CTV volume (1476 cm3).

Conclusion: We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.

目的:颅脊髓照射(CSI)以长期神经内分泌和认知后遗症为代价改善临床结果。本初步研究的目的是确定与标准x射线CSI相比,下丘脑-垂体轴(HPA)和海马回避(HPA- ha)结合强度调节质子治疗(IMPT)是否可以潜在地降低这种发病率。材料和方法:我们回顾性评估了10例髓母细胞瘤患者(平均7岁;范围:4-14年)。靶体积和有危险的器官根据我们的本地方案和ACNS0331地图集进行划定。一位经验丰富的神经放射学家证实了下丘脑和海马体的轮廓。主要目标是CSI和提高临床靶体积(CTV),覆盖95%的体积(D95),稳健性覆盖率> 99%。描述的灰色质子治疗剂量是使用相对于光子治疗1.1的生物有效性来规定的。增强靶的联合规定剂量为54 Gy。次要指标包括HPA和海马复合平均剂量(Dmean≤18 Gy)。对于每个患者,先前存在体积调制电弧放疗(VMAT)和断层治疗(TOMO)计划,并且产生了一个新的计划,即3个颅骨和1或2个脊柱束用于铅笔束扫描递送。采用单因素方差分析进行统计学比较。结果:与标准CSI相比,HPA- ha CSI在HPA接受的复合剂量上有统计学意义的降低(32.2 Gy vs 17.9 Gy;IMPT方案的P均值(17.9 Gy)低于VMAT方案(21.8 Gy)和TOMO方案(21.2 Gy) (P = 0.05)。IMPT组海马复合Dmean (21 Gy)低于VMAT组(27.5 Gy)和TOMO组(27.2 Gy) (P = 0.02)。IMPT方案的IMPT CTV D95覆盖率(52.8 Gy)低于全脑CTV体积(1476 cm3)的VMAT (54.6 Gy)和TOMO (54.6 Gy)方案(p3)。结论:我们发现,与标准x线CSI相比,IMPT在保持靶覆盖的同时,具有降低HPA和海马剂量的强大潜力。需要一项前瞻性临床试验来确定这种新型CSI方法的安全性、有效性和毒性。
{"title":"The Advantage of Proton Therapy in Hypothalamic-Pituitary Axis and Hippocampus Avoidance for Children with Medulloblastoma.","authors":"Saif Aljabab,&nbsp;Shushan Rana,&nbsp;Shadonna Maes,&nbsp;Avril O'Ryan-Blair,&nbsp;Jackie Castro,&nbsp;Jack Zheng,&nbsp;Lia M Halasz,&nbsp;Phillip J Taddei","doi":"10.14338/IJPT-21-00001.1","DOIUrl":"https://doi.org/10.14338/IJPT-21-00001.1","url":null,"abstract":"<p><strong>Purpose: </strong>Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI.</p><p><strong>Materials and methods: </strong>We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D<sub>95</sub>) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (D<sub>mean</sub> ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance.</p><p><strong>Results: </strong>Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; <i>P</i> < .001) and hippocampi (39.8 versus 22.8 Gy; <i>P</i> < .001). The composite HPA D<sub>mean</sub> was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans (<i>P</i> = .05). Hippocampi composite D<sub>mean</sub> was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans (<i>P</i> = .02). The IMPT CTV D<sub>95</sub> coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans (<i>P</i> < .001) The spared mean volume was only 1.35% (19.8 cm<sup>3</sup>) of the whole-brain CTV volume (1476 cm<sup>3</sup>).</p><p><strong>Conclusion: </strong>We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.</p>","PeriodicalId":36923,"journal":{"name":"International Journal of Particle Therapy","volume":"8 3","pages":"43-54"},"PeriodicalIF":1.7,"publicationDate":"2021-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Radiation Necrosis with Proton Therapy in a Patient with Aarskog-Scott Syndrome and Medulloblastoma. 质子放射坏死治疗阿斯科格-斯科特综合征合并髓母细胞瘤1例。
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-07-29 eCollection Date: 2022-01-01 DOI: 10.14338/IJPT-21-00013.1
Vidya Puthenpura, Nicholas J DeNunzio, Xue Zeng, Drosoula Giantsoudi, Mariam Aboian, David Ebb, Kristopher T Kahle, Torunn I Yock, Asher M Marks

Purpose: Medulloblastoma is known to be associated with multiple cancer-predisposition syndromes. In this article, we explore a possible association among a patient's Aarskog-Scott syndrome, development of medulloblastoma, and subsequent brainstem radiation necrosis.

Case presentation: A 5-year-old male with Aarskog-Scott syndrome initially presented to his pediatrician with morning emesis, gait instability, and truncal weakness. He was ultimately found to have a posterior fossa tumor with pathology consistent with group 3 medulloblastoma. After receiving a gross total resection and standard proton beam radiation therapy with concurrent vincristine, he was noted to develop brainstem radiation necrosis, for which he underwent therapy with high-dose dexamethasone, bevacizumab, and hyperbaric oxygen therapy with radiographic improvement and clinical stabilization.

Conclusion: Based on several possible pathologic correlates in the FDG1 pathway, there exists a potential association between this patient's Aarskog-Scott syndrome and medulloblastoma, which needs to be investigated further. In patients with underlying, rare genetic syndromes, further caution should be taken when evaluating chemotherapy and radiation dosimetry planning.

目的:髓母细胞瘤与多种癌症易感综合征有关。在这篇文章中,我们探讨了患者的阿斯科格-斯科特综合征,髓母细胞瘤的发展和随后的脑干放射性坏死之间可能的联系。病例介绍:一名患有阿斯科格-斯科特综合征的5岁男性,最初以晨吐、步态不稳和躯干无力向儿科医生就诊。他最终被发现患有后窝肿瘤,病理与第3组髓母细胞瘤一致。在接受全切除和标准质子束放射治疗并发长春新碱后,他被注意到脑干放射性坏死,为此他接受了大剂量地塞米松、贝伐单抗和高压氧治疗,影像学改善和临床稳定。结论:基于FDG1通路中几个可能的病理相关因素,该患者的Aarskog-Scott综合征与成神经管细胞瘤存在潜在关联,有待进一步研究。对于有潜在的、罕见的遗传综合征的患者,在评估化疗和放射剂量计计划时应进一步谨慎。
{"title":"Radiation Necrosis with Proton Therapy in a Patient with Aarskog-Scott Syndrome and Medulloblastoma.","authors":"Vidya Puthenpura,&nbsp;Nicholas J DeNunzio,&nbsp;Xue Zeng,&nbsp;Drosoula Giantsoudi,&nbsp;Mariam Aboian,&nbsp;David Ebb,&nbsp;Kristopher T Kahle,&nbsp;Torunn I Yock,&nbsp;Asher M Marks","doi":"10.14338/IJPT-21-00013.1","DOIUrl":"https://doi.org/10.14338/IJPT-21-00013.1","url":null,"abstract":"<p><strong>Purpose: </strong>Medulloblastoma is known to be associated with multiple cancer-predisposition syndromes. In this article, we explore a possible association among a patient's Aarskog-Scott syndrome, development of medulloblastoma, and subsequent brainstem radiation necrosis.</p><p><strong>Case presentation: </strong>A 5-year-old male with Aarskog-Scott syndrome initially presented to his pediatrician with morning emesis, gait instability, and truncal weakness. He was ultimately found to have a posterior fossa tumor with pathology consistent with group 3 medulloblastoma. After receiving a gross total resection and standard proton beam radiation therapy with concurrent vincristine, he was noted to develop brainstem radiation necrosis, for which he underwent therapy with high-dose dexamethasone, bevacizumab, and hyperbaric oxygen therapy with radiographic improvement and clinical stabilization.</p><p><strong>Conclusion: </strong>Based on several possible pathologic correlates in the FDG1 pathway, there exists a potential association between this patient's Aarskog-Scott syndrome and medulloblastoma, which needs to be investigated further. In patients with underlying, rare genetic syndromes, further caution should be taken when evaluating chemotherapy and radiation dosimetry planning.</p>","PeriodicalId":36923,"journal":{"name":"International Journal of Particle Therapy","volume":"8 3","pages":"58-65"},"PeriodicalIF":1.7,"publicationDate":"2021-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Insurance Approval for Definitive Proton Therapy for Prostate Cancer. 前列腺癌最终质子治疗的保险批准。
IF 1.7 Q3 ONCOLOGY Pub Date : 2021-07-27 eCollection Date: 2022-01-01 DOI: 10.14338/IJPT-21-00002.1
William M Mendenhall, Eric D Brooks, Stephanie Smith, Christopher G Morris, Curtis B Bryant, Randal H Henderson, Romaine C Nichols, Kathy McIntyre, Stuart L Klein, Nancy P Mendenhall

Purpose: To determine factors that influence insurance approval for definitive proton therapy (PT) for prostate cancer.

Materials and methods: Between 2014 and 2018, 1592 insured patients with localized prostate cancer were evaluated and recommended to undergo definitive PT; 547 patients (34.4%) had commercial insurance, whereas 1045 patients (65.6%) had Medicare/Medicaid. Of those with Medicare, 164 patients (15.7%) had Medicare alone; 677 (64.8%) had supplemental plans; and 204 (19.5%) had secondary commercial insurance. Insurance that "covered" PT for prostate cancer implied that it was an indication designated in the coverage policy. "Not covered" means that the insurance policy did not list prostate cancer as an indication for PT. Of all 1592 patients, 1263 (79.3%) belonged to plans that covered PT per policy. However, approval for PT was still required via medical review for 619 patients (38.9%), comparative dosimetry for 56 patients (3.5%), peer-to-peer discussion for 234 patients (14.7%), and administrative law judge hearings for 3 patients (<0.1%). Multivariate analyses of factors affecting approval were conducted, including risk group (low/intermediate versus high), insurance type (commercial versus Medicare/Medicaid), whether PT was included as a covered benefit under the plan (covered versus not covered), and time period (2014-16 versus 2017 versus 2018).

Results: On multivariate analysis, factors affecting PT approval for prostate treatment included coverage of PT per policy (97.1% had approval with insurance that covered PT versus 48.6% whose insurance did not cover PT; P < .001); insurance type (32.5% had approval with commercial insurance versus 97.4% with Medicare; P < .001); and time, with 877/987 patients (88.9%) approved between 2014 and 2016, 255/312 patients (81.7%) approved during 2017, and 255/293 patients (87.0%) approved thereafter (P = .02). Clinical factors, including risk group, had no bearing on insurance approval (P = .44).

Conclusion: Proton insurance approval for prostate cancer has decreased, is most influenced by the type of insurance a patient belongs to, and is unrelated to clinical factors (risk group) in this study. More work is needed to help navigate appropriate access to care and to assist patients seeking definitive PT for prostate cancer treatment.

目的:探讨影响前列腺癌质子治疗保险批准的因素。材料与方法:2014年至2018年,对1592例局限性前列腺癌参保患者进行评估并推荐行明确的前列腺造影;547名患者(34.4%)有商业保险,1045名患者(65.6%)有医疗保险/医疗补助。在有医疗保险的患者中,164例(15.7%)患者单独有医疗保险;677人(64.8%)有补充计划;204人(19.5%)有二级商业保险。“承保”前列腺癌PT的保险暗示这是保险政策中指定的一种指征。“未包括”是指保单未将前列腺癌列为PT的适应症。在所有1592名患者中,1263名(79.3%)属于每个保单涵盖PT的计划。然而,仍有619例患者(38.9%)、56例患者(3.5%)、234例患者(14.7%)和3例患者需要通过医学审查、比较剂量法、行政法法官听证会来批准PT。结果:在多因素分析中,影响前列腺治疗PT批准的因素包括每个保单的PT覆盖率(97.1%的人批准有PT的保险,48.6%的人批准没有PT的保险;p p p = .02)。临床因素(包括危险组)对保险审批无影响(P = 0.44)。结论:本研究中前列腺癌质子保险审批率有所下降,受患者所属保险类型影响最大,与临床因素(危险人群)无关。需要做更多的工作来帮助患者找到适当的护理途径,并帮助患者寻求前列腺癌治疗的最终治疗方案。
{"title":"Insurance Approval for Definitive Proton Therapy for Prostate Cancer.","authors":"William M Mendenhall,&nbsp;Eric D Brooks,&nbsp;Stephanie Smith,&nbsp;Christopher G Morris,&nbsp;Curtis B Bryant,&nbsp;Randal H Henderson,&nbsp;Romaine C Nichols,&nbsp;Kathy McIntyre,&nbsp;Stuart L Klein,&nbsp;Nancy P Mendenhall","doi":"10.14338/IJPT-21-00002.1","DOIUrl":"https://doi.org/10.14338/IJPT-21-00002.1","url":null,"abstract":"<p><strong>Purpose: </strong>To determine factors that influence insurance approval for definitive proton therapy (PT) for prostate cancer.</p><p><strong>Materials and methods: </strong>Between 2014 and 2018, 1592 insured patients with localized prostate cancer were evaluated and recommended to undergo definitive PT; 547 patients (34.4%) had commercial insurance, whereas 1045 patients (65.6%) had Medicare/Medicaid. Of those with Medicare, 164 patients (15.7%) had Medicare alone; 677 (64.8%) had supplemental plans; and 204 (19.5%) had secondary commercial insurance. Insurance that \"covered\" PT for prostate cancer implied that it was an indication designated in the coverage policy. \"Not covered\" means that the insurance policy did not list prostate cancer as an indication for PT. Of all 1592 patients, 1263 (79.3%) belonged to plans that covered PT per policy. However, approval for PT was still required via medical review for 619 patients (38.9%), comparative dosimetry for 56 patients (3.5%), peer-to-peer discussion for 234 patients (14.7%), and administrative law judge hearings for 3 patients (<0.1%). Multivariate analyses of factors affecting approval were conducted, including risk group (low/intermediate versus high), insurance type (commercial versus Medicare/Medicaid), whether PT was included as a covered benefit under the plan (covered versus not covered), and time period (2014-16 versus 2017 versus 2018).</p><p><strong>Results: </strong>On multivariate analysis, factors affecting PT approval for prostate treatment included coverage of PT per policy (97.1% had approval with insurance that covered PT versus 48.6% whose insurance did not cover PT; <i>P</i> < .001); insurance type (32.5% had approval with commercial insurance versus 97.4% with Medicare; <i>P</i> < .001); and time, with 877/987 patients (88.9%) approved between 2014 and 2016, 255/312 patients (81.7%) approved during 2017, and 255/293 patients (87.0%) approved thereafter (<i>P</i> = .02). Clinical factors, including risk group, had no bearing on insurance approval (<i>P</i> = .44).</p><p><strong>Conclusion: </strong>Proton insurance approval for prostate cancer has decreased, is most influenced by the type of insurance a patient belongs to, and is unrelated to clinical factors (risk group) in this study. More work is needed to help navigate appropriate access to care and to assist patients seeking definitive PT for prostate cancer treatment.</p>","PeriodicalId":36923,"journal":{"name":"International Journal of Particle Therapy","volume":"8 3","pages":"36-42"},"PeriodicalIF":1.7,"publicationDate":"2021-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
期刊
International Journal of Particle Therapy
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