- 作者列表："Kopp B","Mein S","Dokic I","Harrabi S","Böhlen TT","Haberer T","Debus J","Abdollahi A","Mairani A
PURPOSE:To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing. METHODS AND MATERIALS:The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICRC-p treatments using a murine glioma cell line (GL261) was performed. RESULTS:CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/β)x assignment and RBE modeling, the CICRC-p treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUDHe. For both CICRC-p and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICRC-p treatment in heterogenous settings. CONCLUSIONS:Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings.
目的: 在单野布置中开发和验证具有恒定相对生物有效性 (RBE) (CICR) 粒子治疗的联合离子束，以改善治疗效果、稳健性和正常组织保留。 方法和材料: 开发了精确 (使用单一和联合离子优化策略的粒子治疗) 治疗计划系统，以研究CICR治疗的临床可行性。单场均匀剂量 (sfod) 与单离子 (质子 [p]，氦 [He]，或碳 [C]) 和CICR (C-p和C-He) 对 3 例患者病例进行了治疗，临床处方剂量为每部分 3 Gy (RBE)。使用拟人头体模在同质和临床样环境中照射散开的Bragg峰计划。使用鼠胶质瘤细胞系 (GL261) 进行CICRC-p治疗的剂量学和生物学验证。 结果: 与单纯碳离子相比，3 例患者的CICR治疗计划呈现高度均匀的物理剂量，同时降低高剂量平均线性能量转移梯度。当考虑组织参数 (α/β)x分配和RBE建模的不确定性时，CICRC-p治疗在靶体积内表现出增强的生物物理稳定性，类似于单独的质子。CICR治疗减少了靶区周围正常组织的剂量，与SFUDHe相比表现出相似或改善的剂量学特征。对于CICRC-p和SFUD治疗，测量值验证了目标中的计划剂量在 3% 以内。异源环境下CICRC-p治疗的计划与测量目标RBE值分别为 1.38 ± 0.02 和 1.39 ± 0.07 (偏差 <1%)。 结论: 在这里，我们证明了通过在单个场排列中结合 2 个 (或更多) 离子，与常规粒子治疗治疗计划相比，可以提供更稳健的生物和更适形剂量分布。这项工作构成了多离子粒子治疗在均质和异种环境中的首次剂量学和生物学验证。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.