Current status of stereotactic body radiotherapy for lung cancer

Stereotactic radiotherapy (SRT) for extracranial tumors has been recently performed to treat lung and liver cancers, and has subsequently been named stereotactic body radiotherapy (SBRT). The advantages of hypofractionated radiotherapy for treating lung tumors are a shortened treatment course that requires fewer trips to the clinic than a conventional program, and the adoption of a smaller irradiated volume allowed by greater setup precision. This treatment is possible because the lung and liver are considered parallel organs at risk. The preliminary clinical results, mostly reported on lung cancer, have been very promising, including a local control rate of more than 90%, and a relatively low complication rate. The final results of a few clinical trials are awaited. SBRT may be useful for the treatment of stage I lung tumors.     

体部立体定向放疗的放射生物学研究进展

近年来,体部立体定向放疗(SBRT)被越来越多地应用于治疗各种实体肿瘤,并获得了显著的疗效。图像引导系统和放疗技术的进步,使SBRT在靶区内形成高剂量区域,靶区外剂量梯度迅速下降,在给予肿瘤大剂量照射的同时又尽可能地保护周围正常组织,实现了安全的“大分割”。目前,对于SBRT放射生物学尚缺乏规律性的认识,如线性二次(LQ)模型的适用性、再氧合的弱化、不同于常规分割放疗的额外细胞杀伤效应以及免疫增强作用等方面仍存有争议。本综述旨在对以上争议进行分析和探讨,以期加深对SBRT放射生物学特征的认识,进一步促进SBRT的临床应用。     

立体定向体部放疗联合靶向药物治疗转移性肾癌的研究进展

立体定向体部放疗(Stereotactic body radiotherapy, SBRT)是近年来放疗取得的一个突破性进展,具有分次剂量高、生物学效应高、分割次数少等优势,可显著提高肾癌的放疗敏感性。分子靶向治疗显著延长了部分患者的无进展生存期和总生存期,但在大多数情况下产生全身用药的耐药性仍不可避免。近年来,SBRT联合靶向药物治疗转移性肾癌初步显示了有效性和安全性,有可能成为一种更有效的治疗方案。本文针对SBRT联合靶向药物治疗转移性肾癌研究进展进行综述。     

肺部立体定向放疗对外周血淋巴细胞的影响

背景与目的：靶向程序性死亡［蛋白］-1（programmed death-1,PD-1）/程序性死亡［蛋白］配体-1（programmed death ligand-1,PD-L1）的免疫检查点抑制剂已被批准用于多种恶性肿瘤的治疗,其治疗效应的发挥取决于T淋巴细胞的活化。放射治疗诱导的免疫原性细胞死亡可促进免疫反应,但同时辐射诱发的淋巴结细胞减少可能会降低免疫检查点抑制剂的效应。目前不同放疗技术、放疗部位、放疗范围对淋巴细胞的影响都尚不明确。探讨肺部立体定向放疗（stereotactic body radiotherapy,SBRT）的不同分割方式及剂量等参数对患者外周血淋巴细胞的影响。方法：回顾性分析2016—2018年间在郑州大学附属肿瘤医院接受肺部立体定向放疗的64例患者的相关临床资料。SBRT采用90％等剂量线覆盖计划靶体积（planning target volume,PTV）,PTV为40~65 Gy,分割次数4~13次,生物等效剂量（biological equivalent dose,BED）为60~116 Gy,每天1次,每周照射最多5次。通过收集患者放疗前1周、放疗后1周、放疗后1个月和放疗后3个月的血常规数据,分析SBRT的各项参数与患者外周血绝对淋巴细胞计数变化的相关性。结果：外周血淋巴细胞计数在放疗后1周和1个月均出现不同程度的降低,在放疗后3个月基本恢复到放疗前水平。SBRT的各项参数中分割次数对淋巴细胞计数的影响较为突出,在放疗后1周和1个月,分割次数≤5次组的外周血淋巴细胞计数降低程度均显著小于分割次数＞5次组,分别为（1.68±0.63 vs 0.93±0.34,P=0.021）和（1.60±0.68 vs 0.95±0.41,P=0.004）。而不同分割剂量、总剂量、BED值在放疗前后各组对比淋巴细胞计数差异无统计学意义（P＞0.05）。结论：SBRT治疗后1周和1个月,分割次数≤5次组的外周血淋巴细胞计数降低程度显著小于分割次数＞5次组,在SBRT结束后3个月淋巴细计数基本恢复到放疗前水平。     

Double-scattered proton-based stereotactic body radiotherapy for stage I lung cancer: A dosimetric comparison with photon-based stereotactic body radiotherapy

Purpose

Stereotactic body radiotherapy (SBRT) has gained popularity in the treatment of early-stage non-small-cell lung cancer (NSCLC) because of its ability to deliver conformal radiation doses to small targets. However, photon-based SBRT (xSBRT) is associated with significant grade 3+ toxicities. In this study, we compare xSBRT treatment plans with proton-based SBRT (pSBRT) to determine whether dose to normal structures could be reduced if SBRT was delivered with protons.

Materials and methods

Eight patients with medically inoperable, peripherally located stage I NSCLC were treated with xSBRT to 48 Gy in 4 12-Gy fractions. These patients were retrospectively re-planned using the same treatment volumes with 3-dimensional conformal double-scatter proton therapy. A Wilcoxon paired test compared dosimetric parameters between the plans for each patient.

Results

Compared with xSBRT there was a dosimetric improvement with pSBRT for these volumes: lung V5 (median difference [MD] = 10.4%, p = 0.01); V10 (MD = 6.4%, p = 0.01); V20 (MD = 2.1%, p = 0.01); V40 (MD = 1.5%, p = 0.05); and mean lung dose (MD = 2.17 Gy, p = 0.01). There were also benefits (p = <0.05) in D0.1cm3 and D5cm3 with pSBRT to the heart, esophagus, and bronchus.

Conclusions

In a dosimetric comparison between photon and proton-based SBRT, protons resulted in lower doses to critical organs at risk and a smaller volume of non-targeted normal lung exposed to radiation (V5, V10, V20, and V40). The clinical significance and relevance of these dosimetric improvements remain unknown.     

寡转移性乳腺癌的立体定向放疗研究进展

远处转移是乳腺癌患者死亡的主要原因,大多数晚期乳腺癌是不可治愈的。寡转移是介于局限期和广泛转移的一种中间状态。放疗在寡转移性乳腺癌的局部治疗中发挥着非常重要的作用。随着立体定向放疗(SBRT)技术的发展,可以予以根治剂量,同时保护周围的正常组织。既往研究证明SBRT是安全有效的,对乳腺癌的骨、肺、肝、脑、淋巴结等寡转移的局控率>80%。但是,如何筛选真正的寡转移还存在一定争议,进一步的随机临床研究证实放疗能否改善患者生存是至关重要的。     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

Target coverage in image-guided stereotactic body radiotherapy of liver tumors

PURPOSE: To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. METHODS AND MATERIALS: By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV(+), derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. RESULTS: Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. CONCLUSION: Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal imaging.     

Impact of IMRT and leaf width on stereotactic body radiotherapy of liver and lung lesions

PURPOSE: The present study explored the impact of intensity-modulated radiotherapy (IMRT) on stereotactic body RT (SBRT) of liver and lung lesions. Additionally, because target dose conformity can be affected by the leaf width of a multileaf collimator (MLC), especially for small targets and stereotactic applications, the use of a micro-MLC on "uniform intensity" conformal and intensity-modulated SBRT was evaluated. METHODS AND MATERIALS: The present study included 10 patients treated previously with SBRT in our institution (seven lung and three liver lesions). All patients were treated with 3 x 12 Gy prescribed to the 65% isodose level. The actual MLC-based conformal treatment plan served as the standard for additional comparison. In total, seven alternative treatment plans were made for each patient: a standard (actual) plan and an IMRT plan, both calculated with Helax TMS (Nucletron) using a pencil beam model; and a recalculated standard and a recalculated IMRT plan on Helax TMS using a point dose kernel approach. These four treatment plans were based on a standard MLC with 1-cm leaf width. Additionally, the following micro-MLC (central leaf width 3 mm)-based treatment plans were calculated with the BrainSCAN (BrainLAB) system: standard, IMRT, and dynamic arc treatments. For each treatment plan, various target parameters (conformity, coverage, mean, maximal, and minimal target dose, equivalent uniform doses, and dose-volume histogram), as well as organs at risk parameters (3 Gy and 6 Gy volume, mean dose, dose-volume histogram) were evaluated. Finally, treatment efficiency was estimated from monitor units and the number of segments for IMRT solutions. RESULTS: For both treatment planning systems, no significant difference could be observed in terms of target conformity between the standard and IMRT dose distributions. All dose distributions obtained with the micro-MLC showed significantly better conformity values compared with the standard and IMRT plans using a regular MLC. Dynamic arc plans were characterized by the steepest dose gradient and thus the smallest V(6 Gy) values, which were on average 7% smaller than the standard plans and 20% lower than the IMRT plans. Although the Helax TMS IMRT plans show about 18% more monitor units than the standard plan, BrainSCAN IMRT plans require approximately twice the number of monitor units relative to the standard plan. All treatment plans optimized with a pencil beam model but recalculated with a superposition method showed significant qualitative, as well as quantitative, differences, especially with respect to conformity and the dose to organs at risk. CONCLUSION: Standard conformal treatment techniques for SBRT could not be improved with inversely planned IMRT approaches. Dose calculation algorithms applied in optimization modules for IMRT applications in the thoracic region need to be based on the most accurate dose calculation algorithms, especially when using higher energy photon beams.     

IMRT、VMAT及HT技术在肺癌SBRT应用中的比较

肺癌立体定向放疗的主要技术包括调强放疗(IMRT)、容积旋转调强放疗(VMAT)和螺旋断层放疗(HT).3种技术在靶区适形度及剂量均匀性方面,HT和VMAT要优于IMRT,但HT和VMAT技术会增加肺的低剂量区受照体积.VMAT较其他两种技术可明显缩短治疗时间.目前,对于不同位置、不同分期的肺部肿瘤,如何个体化地选择最佳放疗技术仍存有一定的争议.