Total body irradiation (TBI) using volumetric modulated arc therapy (VMAT)

The main clinical requirements of high dose total body irradiation (TBI) are: a uniform dose to the whole body with a variation within ± 10%; reduced dose to critical organs, such as the lungs and kidneys; and delivery of radiation dose with a very low dose rate of around 20-40 cGy/minute^1-3.

以前，最常见的TBI建议方法是使用大型野外（40 x 40 cm）的TBI固定装置，其位于TBI固定装置中的患者（40 x 40 cm），患者位于TBI固定装置中，患者的前后/后置（AP-PA）技术是前后/后前疗法（AP-PA）技术的最常见的方法（40 x 40 cm），最常见的方法是°准直和延伸源至表面距离（SSD）≥4米，以更好地辐射剂量分布。另一种常见的技术是使用平行的对立侧梁。对于这些方法，使用6 mV和10 mV之间的光子能，低剂量速率为15-30 CGY/min1-3。梁扰流板用于增加皮肤剂量，并使用部分传输块将剂量限制为关键器官，例如肺部和肾脏。剂量在脐带水平上向中平面规定，至单点，均匀剂量为±10％，±30％，包括皮肤剂量。建议用于不规则身体轮廓的组织补偿器³.

Conventional extended SSD TBI techniques have many limitations and challenges, including: the impact of the large irregular body contour and tissue inhomogeneity on MU calculation and dose estimation accuracy; non-uniform dose distributions; long patient setup and treatment times due to extended SSD and low dose rate treatment; customization of the treatment box and shields; reproducibility of patient setup, including positioning of lung and kidney shields for upright and lateral setups; difficulties for sick patients to stand for a long time (40-50 minutes), which increase setup inaccuracy^4-5.

近年来,创伤性脑损伤经常计划using modulated arc techniques, such as VMAT and TomoTherapy^5-9. VMAT-based TBI can be implemented safely and is easily accessible to centers where VMAT is already a standard treatment technique^6-9.

VMAT offers a number of advantages for TBI. The patient lies on the couch in a comfortable supine position, which is easier for simulation, improves overall treatment setup, and increases patient comfort. Furthermore, VMAT planning for TBI provides a more conformal and homogenous dose distribution to the target and reduces dose to critical organs, such as the lungs and kidneys (figure 1), and in young patients with benign hematological conditions, reproductive organs. There is no need to customize treatment accessories, such as beam spoilers, treatment frames, and shielding, and it is easy to spare previously treated sites¹⁰.

In 2019, we implemented VMAT TBI at our center to overcome the challenges of conventional extended SSD TBI. The following case study demonstrates how we perform accurate and reliable VMAT TBI using Elekta solutions.

一个18岁的男性与白血球过多(hb - 8.2, TLC-1,35,000) presented in March 2019, and was diagnosed with Philadelphia positive B cell acute lymphoblastic leukaemia refractory to BFM-95 protocol. Since the patient’s disease came under control after three cycles of salvage chemotherapy, he was eligible for allogenic Bone Marrow Transplant (BMT). The conditioning regimen for this procedure includes high-dose cyclophosphamide chemotherapy and total body irradiation (12 Gy in 6 fractions, twice daily for three days).

The patient was simulated for TBI 10 days before BMT on a Discovery IQ (GE healthcare) PET-CT scanner, with a neck rest, a thermoplastic mask for head support, and Elekta BlueBAG™ for body support, using a dedicated TBI CT protocol (table 1). The patient was aligned with lasers and three fiducial markers on the patient’s body (one at head level, a second at chest level, and a third at pelvis level) to ensure reproducible setup for head-first and feet-first setup.

Since this patient was 172 cm in height, he was simulated in head-first supine (HFS) and feet-first supine (FFS) positions. The CT data sets were transferred to Monaco version 5.11.03 for contouring and planning using the Monte Carlo dose calculation algorithm. Delineated structures included the body, lungs, kidneys, liver, eyes, lens, and PTV (cropped 4 mm inside the body and with 3 mm overlap margins with lungs, liver, and kidneys).

Table 1. TBI CT simulation protocol

Patients up to 100 cm length	一个计划CT扫描数据集；首先仰卧（HFS）；5毫米切片厚度。
Patients >100 cm length	Two planning CT scan data sets; head-first supine (HFS) from vertex to lower thigh, up to maximum 150 cm, and feet-first supine (FFS) from toe to pelvis; 5 mm slice thickness.

典型的VMAT TBI计划的详细信息如表2所示。在这种情况下，生成并优化了五个异构体（在纵轴上对齐）和9个VMAT ARC（总）计划（总）计划（总）计划，以在六个级分中均匀剂量，以在六个级分中均匀剂量。三天。该计划的目的是将12 Gy送到PTV的至少90％（V100％≥90％）和11.4 Gy至至少95％的PTV（V95％≥95％）。对于PTV，记录了平均剂量，以及最高剂量的最高剂量（d2 cc）和5 cc（d5 cc），作为最大剂量的指标。据报道，靶标的剂量同质性是剂量的90％（D90％）与最低剂量的最低剂量的比率（最热的10％）（d10％）。

表2.典型的VMAT TBI计划详细信息

Isocenters	3-5 isocenter generated with the same lateral (X) and vertical (Z) coordinates 纵向(Y)坐标与一个固定的整数value
VMAT arcs	5-9 (total) arranged along the longitudinal axis of patient
Photon beam	6 mv gantry increments of 30°
Field size/overlap	all fields optimized to fixed-length field size 4 cm overlap region with the field of other isocenter maximum width of 40 cm
Calculation parameters	grid spacing 0.4 cm calculate dose deposition to medium statistical uncertainty of 1.0% per plan
Sequencing parameters	minimum segment width of 0.5 cm maximum 200 control points per arc fluence smoothing to medium
MLC parameters	有效的叶速度为6.5 cm/s leaf travel of 15 cm over the central axis jaws speed of 9 cm/s across dynamic segments
HFS/FFS	对于与HFS CT数据集融合的FFS，偏置剂量用于在交界处管理高剂量 a 1-2 isocenter (depending on patient length) AP-PA plan is used to treat the lower body (FFS).

OAR constraints aimed to restrict mean lung dose to < 8 Gy for each lung and combined lung volumes and reduce dose by 15% to the liver and by 30% to the kidneys, while keeping maximum dose and dose homogeneity within acceptable ranges.

During planning phase 1 (theoretical fluence optimization) Multi Criteria Optimization (MCO) was used to decrease OAR dose as much as possible, without compromising the target coverage. Then, in phase 2 (sequencing and segment creation), MCO was toggled off to give Segment Shape Optimization (SSO) more degrees of freedom to converge towards full target coverage.

Dosimetric parameters achieved for this treatment plan are shown in table 3. Although the mean lung doses were slightly higher than plan objectives, they were deemed clinically acceptable. The PTV had an overlap of 3 mm with the lungs to compensate for respiratory motion. Therefore, the higher planning dose covered the peripheral lung, and the central lung was spared.

Table 3. Dosimetric parameters for VMAT TBI plan

Volume	参数/标准	Achieved
PTV	V100% ≥ 90% V95% ≥ 95%	90.2% 96.57%
	Homogeneity (D90/D10)	0.90
	D2cc D5cc D10cc	13.70 GY 13.60 Gy 13.32 Gy
Lungs	Mean dose right lung (< 8 Gy) Mean dose left lung (< 8 Gy)	8.3 Gy 8.6 Gy
Kidneys	Mean dose right kidney (reduced by 30%) Mean dose left kidney (reduced by 30%)	8.2 Gy 7.8 Gy
Liver	Mean dose (reduced by 15%)	10.4 Gy

Quality assurance for VMAT TBI plans is performed using an Octavius 4D phantom (PTW, Germany). The 3D dose fluence of the VMAT plan is measured for individual isocenters. Dosimetric accuracy between planned and delivered dose is evaluated using gamma index analysis with criteria of 3 mm and 3% in all 3 planes. Chest field QA results for this patient, for the lungs in the coronal plane, are shown in figure 2.

Point dose measurements for all isocenters are also performed, using an Octavius phantom with a 0.07 cm³Semiflex 3D ion chamber (PTW, Germany). Dose calculation and delivery accuracy between the junctions of isocenters are verified with the point dose measurement at three different points at each junction.

The patient was treated twice daily for three days, with a minimum inter-fraction gap of 6 hours. The patient was aligned using the three fiducials and a laser with index setup procedure to ensure reproducibility. Patient setup was verified using XVI 5.0 kV cone-beam CT (CBCT) image guidance and planned kV images for all isocenters before each fraction delivery. Intra-fraction kV imaging was also performed to monitor patient motion during treatment delivery.

The only radiation-associated toxicity noted during and after radiation treatment was nausea (grade 2). Mucositis and dermatitis were not reported.

The patient was successfully treated with TBI and BMT. He recovered and was discharged after one month. The patient is alive and disease-free at D+300, without any significant Graft Versus Host (GVHD), and regularly attends for routine follow-up.

5毫米的叶宽度、40 * 40厘米大小,nd effective leaf speed of 6.5 cm/s (combined with the jaw speed of 9 cm/s) of Agility, Monaco effectively optimized the VMAT plan to achieve uniform and homogeneous dose to the large PTV, while restricting OAR dose effectively with the system's virtual 1 mm leaf width capabilities. In addition, since VMAT TBI requires a high number of MUs, Agility’s very low transmission (less than 0.5% for 6 MV) helps to reduce the contribution of transmission dose to the VMAT TBI plan.

Monaco’s XVMC Monte Carlo dose engine calculates the continuous arc as a single beam, rather than approximating dose at many discrete (control point) gantry angle positions. The Monte Carlo algorithm optimizes and calculates dose accurately for tissues of different heterogeneity, such as the lung and PTV interface. By optimizing multiple isocenters in a single optimization, utilizing MCO to reduce OAR dose as much as possible, Monaco reduces planning time and improves overall plan quality. The high-dose junction regions between the two data sets were eliminated by registering two CT data sets using the bias-dose functionality of Monaco 5.11.

VMAT TBI本质上是复杂的，这是由于使用了3​​-5个同中心，多个VMAT弧，HFS和FFS方向进行治疗以及其长期治疗时间。在这些方面影响治疗不确定性的情况下，该技术的挑战之一是确保精确的患者设置。加上严格的患者固定和适当的患者标记，设置不确定性通过预处理和验证内KV成像最小化。Linac的开放设计和大量清除允许在不损害患者设置的情况下轻松进行预处理和验证内成像。表面图像引导的放射治疗（SIGRT）的实施可以进一步减少由施法内运动引起的设置误差。

使用VMAT的TBI提高了部门的生产率，因为它的劳动力较少，而不是传统的TBI。VMAT方法允许患者处于舒适的仰卧位置，而无需定制的支架或盾牌放置，节省了大量的设置和验证时间。XVI成像也快速准确，用于治疗设置验证和分数内运动监测。由于VMAT TBI的平均治疗时间为40-50分钟，因此患者运动监测对于OAR保留很重要。如果在治疗过程中检测到换档，则施法成像允许进行必要的校正。

The homogenous dose coverage and OAR sparing that can be achieved using VMAT provide confidence to treat patients using complex, whole body, high dose TBI accurately and reliably. Patient outcomes are good, with a maximum of grade 2 toxicity.

具有高级，具有VMAT能力的Linac中心的中心可以使用VMAT TBI治疗患者，而无需修改Linac Bunker。此外，由于我们的辐射肿瘤学人员非常熟悉VMAT治疗计划和交付，因此无需进行特殊培训。

The use of VMAT is currently being evaluated in clinical trials for the delivery of more targeted TBI, referred to as total marrow and lymphoid irradiation (TMLI)11. This technique offers a high degree of dose conformity, dose homogeneity, significantly lower organ doses, reduced toxicity, dose escalation to target structures, and reduced relapse rates. It is hoped that our learning experience with VMAT TBI will help to ease the implementation of VMAT TMLI in our department.

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