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.

     

Image-guidance for stereotactic body radiation therapy.

The term stereotactic body radiation therapy (SBRT) describes a recently introduced external beam radiation paradigm by which small lesions outside the brain are treated under stereotactic conditions, in a single or few fractions of high-dose radiation delivery. Similar to the treatment planning and delivery process for cranial radiosurgery, the emphasis is on sparing of adjacent normal tissues through the creation of steep dose gradients. Thus, advanced methods for assuring an accurate relationship between the target volume position and radiation beam geometry, immediately prior to radiation delivery, must be implemented. Such methods can employ imaging techniques such as planar (e.g., x-ray) or volumetric (e.g., computed tomography [CT]) approaches and are commonly summarized under the general term image-guided radiation therapy (IGRT). This review summarizes clinical experience with volumetric and ultrasound based image-guidance for SBRT. Additionally, challenges and potential limitations of pre-treatment image-guidance are presented and discussed.     

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.     

Daily online adaptive magnetic resonance image (MRI) guided stereotactic body radiation therapy for primary renal cell cancer

Stereotactic body radiotherapy (SBRT) has demonstrated promising outcomes for patients with early-stage, medically inoperable, primary renal cell carcinoma (RCC) in large multi-institutional studies and prospective clinical trials. The traditional approach used in these studies consisted of a CT-based planning approach for target and organ-at-risk (OAR) volume delineation, treatment planning, and daily treatment delivery. Alternatively, MRI-based approaches using daily online adaptive radiotherapy have multiple advantages to improve treatment outcomes: (1) more accurate delineation of the target volume and OAR volumes with improved soft tissue visualization; (2) gated beam delivery with biofeedback from the patient; and (3) potential for daily plan adaptation due to changes in anatomy to improve target coverage, reduce dose to OARs, or both. The workflow, treatment planning principles, and aspects of treatment delivery specific to this technology are outlined using a case example of a patient with an early-stage RCC of the right kidney treated with MRI-guided SBRT using daily adaptive treatment to a dose of 42 Gy in 3 fractions.     

Specific toxicity after stereotactic body radiation therapy to the central chest

The toxicity of stereotactic body radiation therapy in the central chest remains an unsettled issue. The collected data concerning the observed complications are poorly understood and are limited in their quantity and quality, thus hampering a precise delineation of treatment-specific toxicity. The majority of complications scored as toxicity grade 5, namely respiratory failure and fatal hemoptysis, are most likely related to multiple competing risks and occurred at different dose fractionation schemas, e.?g., 10–12 fractions of 4–5 Gy, 5 fractions of 10 Gy, 3 fractions of 20–22 Gy, and 1 fraction of 15–30 Gy. Further investigations with longer follow-up and more details of patients’ pretreatment and tumor characteristics are required. Furthermore, satisfactory documentation of complications and details of dosimetric parameters, as well as limitation of the wide range of possible fractionation schemes is also warranted for a better understanding of the risk factors relevant for macroscopic damage to the serially organized anatomic structure within the central chest.     

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。     

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.     

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。     

三种验证设备在立体定向放射治疗的剂量验证结果分析

目的 比较靶区体积、计算网格和剂量阈值等参数对ArcCHECK、SRS MapCHECK和3DMap 3种验证设备的立体定向放射治疗剂量验证结果的影响。方法 选取50例立体定向放疗计划,分别比较靶区体积(<25 cm³和≥25 cm³)、计算网格(1.0、1.5和2.0 mm)和剂量阈值(5%、10%和15%)对3种验证设备3 mm/3%、3 mm/2%、3 mm/1%、2 mm/3%和 2 mm/2%的γ通过率的影响。结果 靶区体积的改变对于3DMap的影响较大,与小体积相比,3DMap大体积的3 mm/3%、3 mm/2%、2 mm/3%和2 mm/2%的γ通过率分别增加2.2%、2.2%、4.4%和4.7%(t=-2.76、-2.17、-4.72、-3.86,P<0.05);计算网格1.5和1.0 mm相比,对于MapCHECK的影响较大,5种γ通过率分别降低0.7%、1.1%、1.7%、0.9%和1.5%(t=-6.15、 -6.23、-5.98、-5.11、-8.34,P<0.05)。计算网格2.0和1.0 mm相比,对于ArcCHECK影响较大,5种γ通过率分别降低1.0%、1.7%、2.4%、1.7%和2.7%(t=-4.75、-7.30、 -8.63、 -7.11、-8.26,P<0.05);剂量阈值10%和5%相比,对于ArcCHECK影响较大,3 mm/3%、 3 mm/2%、2 mm/3%和2 mm/2%的γ通过率分别降低0.5%、0.8%、1.2%和1.7% (t=5.20、5.68、8.17、9.99,P<0.05)。剂量阈值15%和5%相比,对于3DMap的影响较大,3 mm/3%、 3 mm/2%、2 mm/3%和2 mm/2%的γ通过率分别降低1.6%、1.7%、2.8%和3.2%(t=3.25、2.98、4.40、4.21,P<0.05)。结论 靶区体积、计算网格和剂量阈值对3种验证设备立体定向放疗计划的验证通过率产生不同程度的影响。在临床使用时应对于不同的验证设备具体考虑这些参数对于验证结果的影响。     

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.     

Optical tracking technology in stereotactic radiation therapy.

The last decade has seen the introduction of advanced technologies that have enabled much more precise application of therapeutic radiation. These relatively new technologies include multileaf collimators, 3-dimensional conformal radiotherapy planning, and intensity modulated radiotherapy in radiotherapy. Therapeutic dose distributions have become more conformal to volumes of disease, sometimes utilizing sharp dose gradients to deliver high doses to target volumes while sparing nearby radiosensitive structures. Thus, accurate patient positioning has become even more important, so that the treatment delivered to the patient matches the virtual treatment plan in the computer treatment planning system. Optical and image-guided radiation therapy systems offer the potential to improve the precision of patient treatment by providing a more robust fiducial system than is typically used in conventional radiotherapy. The ability to accurately position internal targets relative to the linac isocenter and to provide real-time patient tracking theoretically enables significant reductions in the amount of normal tissue irradiated. This report reviews the concepts, technology, and clinical applications of optical tracking systems currently in use for stereotactic radiation therapy. Applications of radiotherapy optical tracking technology to respiratory gating and the monitoring of implanted fiducial markers are also discussed.     

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.     

基于容积旋转弧形调强放疗技术的肝癌立体定向放疗方案评估与位置误差分析

目的 基于容积旋转弧形调强放疗（VMAT）技术,对肝癌立体定向放疗（SABR）方案进行评估,并结合图像引导技术及呼吸管理技术,分析执行中患者位置误差。方法 回顾性分析接受基于VMAT技术的SABR治疗并配合自主深呼气末屏气技术（vDEBH）进行呼吸管理的15例肝癌患者。VMAT计划采用2个部分弧,对治疗方案评估剂量参数,比较VMAT与调强放疗技术（IMRT）的计划质量差异。所有优化方案均经质量保证（QA）验证,包括点剂量和面剂量验证、机器跳数（MU）和出束时间记录。每次治疗时,锥形束CT（CBCT）影像采集2次,包括治疗前1次评估两次治疗间误差和治疗结束后1次评估当次治疗内位移。结果 VMAT和IMRT优化方案的各剂量学参数均满足临床治疗要求,差异无统计学意义（P>0.05）;相比IMRT,VMAT方案的平均MU降低了28.1%（t=3.064,P<0.05）,且治疗时间缩短了31.6%（t=2.278,P<0.05）。CBCT图像引导结果显示,采用vDEBH技术可有效减少当次治疗内的位置误差,各方向上的偏移均控制在可容许范围内（<3 mm）。结论 基于VMAT技术的肝癌SABR治疗计划在靶区体积剂量分布和正常组织受量等剂量学表现与IMRT技术相当,可行性良好且在治疗效率方面优势明显。     

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).