The radiobiological effect of using Acuros XB vs anisotropic analytical algorithm on hepatocellular carcinoma stereotactic body radiation therapy

The purpose of this work was to study the radiobiological effect of using Acuros XB (AXB) vs Analytic Anisotropic Algorithm (AAA) on hepatocellular carcinoma (HCC) stereotactic body radiation therapy (SBRT). Seventy SBRT volumetric modulated arc therapy (VMAT) plans for HCC were calculated using AAA and AXB respectively with the same treatment parameters. Published tumor control probability (TCP) and normal tissue complication probability (NTCP) models were used to quantify the effect of dosimetric difference between AAA and AXB on TCP, NTCP and uncomplicated tumor control probability (UTCP). There was an average decrease of 2.5% in 6-month TCP. Normal liver has the largest average decrease in NTCP which was 59.7%. Bowels followed with 26.6% average decrease in NTCP. Duodenum, stomach and esophagus had 10.2%, 5.1%, and 4.3% average decrease in NTCP. There was an average decrease of 1.8% and up to 7.2% in 6-month UTCP. There was an overall decrease in TCP, NTCP, and UTCP for HCC SBRT plans calculated using AXB compared to AAA which could be clinically significant.     

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer

Purpose

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Methods

From 2012 to 2016, 106 patients (median age 74 years, range 50–94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent ¹⁸F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1–3?cm) in 86 patients (81%) and IIA (T2a/b, 3–5?cm) in 20?patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5?Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%.

Results

Median follow-up was 15 months (range 0.5–46 months). Acute side effects were mild (fatigue grade 1–2 in 20% and dyspnea grade 1–2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80–96%) at 2 years and 77% (95%CI 56–98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23–31 months). Overall survival was 77% (95%CI 65–85%) at 2 years and 56% (95%CI 39–73%) at 3 years.

Conclusion

CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

     

Primary non-small cell lung cancer in a transplanted lung treated with stereotactic body radiation therapy

The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression.     

Radiation pneumonitis after stereotactic radiation therapy for lung cancer

Stereotactic body radiation therapy (SBRT) has a local control rate of 95% at 2 years for non-small cell lung cancer (NSCLC) and should improve the prognosis of inoperable patients, elderly patients, and patients with significant comorbidities who have early-stage NSCLC. The safety of SBRT is being confirmed in international, multi-institutional Phase II trials for peripheral lung cancer in both inoperable and operable patients, but reports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer. Radiation pneumonitis (RP) is one of the most common toxicities of SBRT. Although most post-treatment RP is Grade 1 or 2 and either asymptomatic or manageable, a few cases are severe, symptomatic, and there is a risk for mortality. The reported rates of symptomatic RP after SBRT range from 9% to 28%. Being able to predict the risk of RP after SBRT is extremely useful in treatment planning. A dose-effect relationship has been demonstrated, but suggested dose-volume factors like mean lung dose, lung V20, and/or lung V2.5 differed among the reports. We found that patients who present with an interstitial pneumonitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumonitis after SBRT. At our institution, lung cancer patients with these risk factors have not received SBRT since 2006, and our rate of severe RP after SBRT has decreased significantly since then.     

Dosimetric errors during treatment of centrally located lung tumors with stereotactic body radiation therapy: Monte Carlo evaluation of tissue inhomogeneity corrections

Early experience with stereotactic body radiation therapy (SBRT) of centrally located lung tumors indicated increased rate of high-grade toxicity in the lungs. These clinical results were based on treatment plans that were computed using pencil beam–like algorithms and without tissue inhomogeneity corrections. In this study, we evaluated the dosimetric errors in plans with and without inhomogeneity corrections and with planning target volumes (PTVs) that were within the zone of the proximal bronchial tree (BT). For 10 patients, the PTV, lungs, and sections of the BT either inside or within 2 cm of the PTV were delineated. Two treatment plans were generated for each patient using the following dose-calculation methods: (1) pencil beam (PB) algorithm without inhomogeneity correction (IC) (PB ? IC) and (2) PB with inhomogeneity correction (PB + IC). Both plans had identical beam geometry but different beam segment shapes and monitor units (MU) to achieve similar conformal dose coverage of PTV. To obtain the baseline dose distributions, each plan was recalculated using a Monte Carlo (MC) algorithm by keeping MUs the same in the respective plans. The median maximum dose to the proximal BT and PTV dose coverage in the PB + IC plans were overestimated by 8% and 11%, respectively. However, the median maximum dose to the proximal BT and PTV dose coverage in PB ? IC plans were underestimated by 15% and 9%. Similar trends were observed in low-dose regions of the lung within the irradiated volume. Our study indicates that dosimetric bias introduced by unit tissue density plans cannot be characterized as underestimation or overestimation of dose without taking the tumor location into account. This issue should be considered when analyzing clinical toxicity data from early lung SBRT trials that utilized unit tissue density for dose calculations.     

Exploiting tumor position differences between deep inspiration and expiration in lung stereotactic body radiation therapy planning

Purpose: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. Methods: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. Results: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. Conclusions: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.     

A preliminary experience of moderate-intensity stereotactic body radiation therapy for ultra-central lung tumor

Abstract

Purpose: Administration of stereotactic body radiation therapy (SBRT) to ultra-central (UC) lung tumors, generally defined as those abutting the proximal bronchial trees, is difficult due to concerns about serious toxicities. Therefore, our institution has performed moderate-intensity SBRT.

Patients and methods: Patients with UC tumors underwent SBRT at a dose of 50–60?Gy in 10 fractions, with D_max in the target volume not exceeding 110% of the prescribed dose. The primary outcomes were tumor response and overall survival (OS).

Results: From January 2017 to September 2018, we treated eight patients who had been diagnosed with UC tumors. The median follow-up time was 8.6 months (range: 2.7–14.9). Five of the eight patients (62.5%) showed a complete response (CR), two (25%) had a partial response (PR), and one (12.5%) had stable disease (SD); the response and disease control rates were 87.5% and 100%, respectively. Seven patients were alive with no evidence of disease or with controlled disease until the last follow-ups, except for one patient who died due to a non-RT cause at 3 months after SBRT. One patient experienced grade 2 esophageal pain and another had grade 1 cough. No grade 3 or higher toxicities were reported.

Conclusion: Moderate-intensity SBRT might aid in achieving good control of UC tumors without excessive toxicities. Future studies involving larger numbers of patients and longer follow-up times are warranted to confirm the efficacy and feasibility.     

Radiation bronchitis in lung cancer patient treated with stereotactic radiation therapy

We report a case of chronic radiation bronchitis that developed in a patient with lung cancer treated with fractionated stereotactic radiation therapy. A 73-year-old woman with a medically inoperable T1N0M0 adenocarcinoma of the lung was treated with stereotactic radiation therapy. By using eight non-coplanar ports, 50 Gy/5 fractions was delivered in two weeks. At four weeks, a partial response was obtained with no acute adverse reaction. She developed severe cough at six months. Fiberoptic bronchoscopy revealed thick circumferentially coated bronchial mucosa in close proximity to the tumor site. At 12 months, follow-up study confirmed marked stenotic change in the B6 segmental bronchus without tumor progression.     

FDG PET/CT texture analysis for predicting the outcome of lung cancer treated by stereotactic body radiation therapy

Introduction

With ¹⁸F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether ¹⁸F-FDG uptake intensity, volume or heterogeneity could predict the outcome in patients with non-small cell lung cancers (NSCLC) treated by stereotactic body radiation therapy (SBRT).

Methods

Sixty-three patients with NSCLC treated by SBRT underwent a ¹⁸F-FDG PET/CT before treatment. Maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), as well as 13 global, local and regional textural features were analysed. The predictive value of these parameters, along with clinical features, was assessed using univariate and multivariate analysis for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Cutoff values were obtained using logistic regression analysis, and survivals were compared using Kaplan-Meier analysis.

Results

The median follow-up period was 27.1 months for the entire cohort and 32.1 months for the surviving patients. At the end of the study, 25 patients had local and/or distant recurrence including 12 who died because of the cancer progression. None of the clinical variables was predictive of the outcome, except age, which was associated with DFS (HR 1.1, P?=?0.002). None of the ¹⁸F-FDG PET/CT or clinical parameters, except gender, were associated with OS. The univariate analysis showed that only dissimilarity (D) was associated with DSS (HR?=?0.822, P?=?0.037), and that several metabolic measurements were associated with DFS. In multivariate analysis, only dissimilarity was significantly associated with DSS (HR?=?0.822, P?=?0.037) and with DFS (HR?=?0.834, P?<?0.01).

Conclusion

The textural feature dissimilarity measured on the baseline ¹⁸F-FDG PET/CT appears to be a strong independent predictor of the outcome in patients with NSCLC treated by SBRT. This may help selecting patients who may benefit from closer monitoring and therapeutic optimization.

     

立体定向放射治疗在结直肠癌肝转移中的临床应用

目的 评价立体定向放射治疗（SBRT）在结直肠癌肝转移（CLM）中的治疗效果,为合理选择治疗手段提供依据。方法 解放军306医院收治的28例患者,包括男17例,女11例,中位年龄63.8岁（31~86岁）,共计54个病灶,行立体定向放射治疗。平静呼吸状态下的CT增强扫描影像分别进行大体肿瘤体积（GTV）、临床靶区体积（CTV）和计划靶区体积（PTV）的勾画,CTV为GTV外放5 mm,GTV为CTV外放5~10 mm。以50%~60%等剂量曲线作为处方剂量曲线,单次3~6 Gy,总剂量39~45 Gy,等效生物剂量50.7~65.3 Gy。治疗后3个月开始复查,以增强CT或MR显示的病灶体积的变化做为评价疗效的依据。根据RTOG毒性诊断标准对不良反应进行诊断和分级,比较局控率和生存率。结果 所有患者均顺利完成治疗,中位随访时间为15.1个月（3~30个月）,随访终点有7例患者存活。局控率为79.2%,1年和2年的总生存率分别为82.7%和48.6%。病灶体积与局控率关系密切,当体积小于14 cm³时,肿瘤局控率明显高于病灶体积大于65 cm³时（χ² = 4.17,P<0.05）。病灶体积大于180 cm³时,肿瘤局控率为零。不良反应包括治疗后乏力（60.7%）,1、2级消化道反应（28.6%）,一过性1、2级骨髓抑制（46.4%）,一过性转氨酶增高（17.8%）。全组未发生3级以上及晚期不良反应。结论 立体定向放射治疗可做为选择性病例尤其是不能手术的结直肠癌肝转移患者的首选局部治疗手段。     

肺癌调强计划在水与介质中蒙特卡罗计算的剂量差异

目的 探讨肺癌调强放疗计划时,蒙特卡罗算法计算对水与介质的剂量差异。方法随机类型抽样法选取10例肺癌患者的5野调强计划,在质量保证模块下以患者自身图像为模体,采用蒙特卡罗算法分别计算两种计划的吸收剂量,计算对实际介质的吸收剂量(D_m)和对水的吸收剂量(D_w);通过剂量体积直方图的剂量体积参数和计划分析,比较两种剂量在患者体内的分布差异。结果 靶区PTV65和PTV50的D_50%、D_98%和D_2%的D_m和D_w差异分别为:-0.3%、-0.2%、0.3%和0.1%、-0.6%、0.4%,其中PTV65的D_50%和PTV50的D_98%差异有统计学意义(t=-2.536、-3.776,P<0.05)。正常组织的D_50%中,脊髓、心脏、肺和食管的D_m与D_w的平均偏差为0.3%、1.1%、-0.2%和-0.1%,脊髓和心脏的D_m比D_w稍低(t=2.535、3.254,P<0.05);正常组织的D_2%的平均偏差为0.3%、-0.6%、-0.7%和0.6%,差异有统计学意义(t=2.311、-4.105、-3.878、6.214,P<0.05)。所有剂量的体积偏差均<2%。对于没有勾画出来的一些骨组织区域,D_m和D_w的偏差>5%。结论 在临床使用过程中,在考虑骨性组织的受照剂量限制时,需要注意肺癌患者的D_m与D_w的相对偏差。     

Frame-based immobilization and targeting for stereotactic body radiation therapy.

Frame-based stereotactic body radiation therapy (SBRT), such as that conducted with Elekta's Stereotactic Body Frame, can provide an extra measure of precision in the delivery of radiation to extracranial targets, and facilitates secure patient immobilization. In this paper, we review the steps involved in optimal use of an extra-cranial immobilization device for SBRT treatments. Our approach to using frame-based SBRT consists of 4 steps: patient immobilization, tumor and organ motion control, treatment/planning correlation, and daily targeting with pretreatment quality assurance. Patient immobilization was achieved with the Vac-Loc bag, which uses styrofoam beads to conform to the patient's shape comfortably within the body frame. Organ and motion control was assessed under fluoroscopy and controlled via a frame-mounted abdominal pressure plate. The compression screw was tightened until the diaphragmatic excursion range was < 1 cm. Treatment planning was performed using the Philips Pinnacle 6.2b system. In this treatment process, a 20 to 30 noncoplanar beam arrangement was initially selected and an inverse beam weight optimization algorithm was applied. Those beams with low beam weights were removed, leaving a manageable number of beams for treatment delivery. After planning, daily targeting using computed tomography (CT) to verify x-, y-, and z-coordinates of the treatment isocenter were used as a measure of quality assurance. We found our daily setup variation typically averaged < 5 mm in all directions, which is comparable to other published studies on Stereotactic Body Frame. Treatment time ranged from 30 to 45 minutes. Results demonstrate that patients have experienced high rates of local control with acceptable rates of severe side effects - by virtue of the tightly constrained treatment fields. The body frame facilitated comfortable patient positioning and quality assurance checks of the tumor, in relation to another set of independent set of coordinates defined by the body frame fiducials. The ability to impose abdominal compression proved to be a simple way to reduce target and tissue motion. SBRT with Stereotactic Body Frame enables comfortable patient immobilization and facilitates repeated registering and re-registering of the patient to the frame. With the body frame, large-dose-per fraction treatment is possible for localized tumor deposits with the aim of attaining a more therapeutic result.     

Radiation injury of the lung after stereotactic body radiation therapy (SBRT) for lung cancer: A timeline and pattern of CT changes

Stereotactic body radiation therapy (SBRT) is a new radiotherapy treatment method that has been applied to the treatment of Stage I lung cancers in medically inoperable patients, with excellent clinical results. SBRT allows the delivery of a very high radiation dose to the target volume, while minimizing the dose to the adjacent normal tissues. As a consequence, CT findings after SBRT have different appearance, geographic extent and progression timeline compared to those following conventional radiation therapy for lung cancer. In particular, SBRT-induced changes are limited to the “shell” of normal tissue outside the tumor and have a complex shape. When SBRT-induced CT changes have a consolidation/mass-like appearance, the differentiation from tumor recurrence can be very difficult. An understanding of SBRT technique as it relates to the development of SBRT-induced lung injury and familiarity with the full spectrum of CT manifestations are important to facilitate diagnosis and management of lung cancer patients treated with this newly emerging radiotherapy method.     

Monte Carlo modelling of acute and late effects in radiation therapy

Physical models are increasingly used to predict acute and late effects resulting from radiation therapy. These models utilise measured and calculated microdosimetric quantities, and are increasingly used to determine the significant corrections for effective dose used in ion-beam therapy, neutron therapy and boron neutron-capture therapy. The relative biological effect (RBE) of differing radiation sources is predicted using measurable quantities such as lineal energy, which have been also generally been reproduced with calculations using Monte Carlo methods. In addition to the physical data provided by Monte Carlo modelling, in vitro studies and epidemiological data derived from cancer treatments and other exposed populations, are used in the prediction of the risk of late effects such as secondary malignancies. Monte Carlo methods are used in particular to model contaminant components. This work focuses on our understanding of the variation in RBE in photon and electron radiotherapy, how it might affect precision in the treatment of cancer, and how it provides an accurate starting point in extrapolating to prescribed doses with new therapies. In vitro transformation assays and Monte Carlo based calculations of bioeffect used for conventional photon therapy treatments over a range of energies are examined and their utility in the refinement of bioeffect models for both early and late effects are discussed.     

立体定向放疗应用于肺寡转移灶的疗效与预后

目的 分析立体定向放射治疗（stereotactic body radiation therapy,SBRT）应用于肺寡转移灶的疗效与预后。方法 回顾性分析2012-2018年本院SBRT肺寡转移患者104例临床资料,2015年12月前的患者采用调强放疗（intensity modulated radiation therapy,IMRT）技术行立体定向放射治疗,2015年12月后的患者采用螺旋断层放疗（helical tomotherapy,HT）技术行立体定向放射治疗,用Kaplan-Meier方法计算局部控制（local control,LC）、无进展生存期（progression-free survival,PFS）及总生存（overall survival,OS）,Cox回归模型进行单因素与多因素分析,NCICTCAE V4.0标准评价放疗的不良反应。结果 1、2、3年的LC分别为86.6%、75.9%、72.3%,PFS分别为40.9%、28.4%、22.1%,OS分别为75.9%、53.2%、43.53%,中位OS为26.6个月。多因素分析显示原发肿瘤的病理类型、肺部结节的体积及SBRT治疗前癌胚抗原水平（carcino-embryonic antigen,CEA）为LC的独立预后因素（χ²=28.66,P<0.05）,SBRT后的进展方式为OS的独立预后因素（χ²=40.01,P<0.05）,HT-SBRT与IMRT-SBRT的LC及OS差异无统计学意义（P>0.05）;治疗的主要不良反应为放射性肺炎（25例,24.04%）,2级及以上放射性肺炎的发生率不超过7%。结论 SBRT应用于肺寡转移灶的治疗局部控制率高,不良反应可接受,HT-SBRT与IMRT-SBRT的疗效相当,不良反应差异无统计学意义,可广泛应用于临床。     

Computed tomography appearances of local recurrence after stereotactic body radiation therapy for stage I non-small-cell lung carcinoma

Purpose  

The aim of this study was to characterize computed tomography (CT) manifestations of local recurrence after stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC).