Case Study

Single isocenter high definition dynamic radiosurgery (HDRS) for multiple brain metastasesHDRS with Monaco®, Versa HD™ and HexaPOD™allows multiple brain metastases treatment within standard 15-minute timeslots.

InstitutionFarrer Park Hospital

LocationSingapore

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Lip Teck Chew, Chief Medical Physicist Hooi Yin Lim, Medical Physicist Dr. Khai Mun Lee, Radiation Oncology Consultant

Summary

Contributors

Patient demographics: 49-year-old male, diagnosed with hard palate osteosarcoma with lung metastasis in December 2013, presented with multiple brain metastases

Previous treatments include: Chemotherapy, resection, radiotherapy to the primary site and lung SBRT

Treatment: · Single isocenter brain SRS (25.5 Gy in

3 fractions) to 3 targets

· 4 VMAT arcs

· 6 MV flattening filter free (FFF) beam

· Each fraction delivered within a 15-minute appointment

Diagnosis: Stage 4 hard palate osteosarcoma with multiple brain metastases

Treatment planning and delivery system: · Fraxion™ cranial immobilization

· Monaco® treatment planning system version 5.11

· Versa HD™

· XVI and HexaPOD™ evo RT System

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Patient history and diagnosisThis 49-year-old male patient was previously diagnosed with hard palate osteosarcoma with lung metastasis in December 2013. At that time, the patient was treated with multiple lines of chemotherapy, including cisplatin/doxorubicin/avastin and high dose methotrexate, with a resection and radiotherapy to the primary site.

In April 2017, PET-CT demonstrated fluorodeoxyglucose (FDG) avid soft tissue thickening in the right cheek, inferior temporal fossa, along the anterior maxilla margin and zygoma. This appeared generally stable in extent, but with mixed metabolic response. PET-CT also revealed progressive lung metastases with increase in size and metabolic activity. A left lower lobe lesion measured 2.3 x 3.5 cm and a right upper lobe lesion measured 4.7 x 3.8 cm.

Additional suspected metastases were observed as follows: interval new FDG avid lesions were present in the left gluteal muscle; interval new FDG avid calcific foci were seen in the right pectoralis major muscle and right soleus muscle; there was an interval new FDG avid calcified lesion in the right occipital lobe, with associated adjacent vasogenic edema; and there was an interval new FDG avid lesion in the right proximal femur. The lung metastases were treated using stereotactic body radiotherapy (SBRT) in May 2017. The patient received 45 Gy over five fractions to each lesion in the left and right lungs independently, delivered on alternate days. PET-CT assessment in October 2017 revealed that the lung metastases were larger in size (left lung: 2.6 x 3.4 cm; right lung: 5.5 x 4.3 cm), but showed decreased metabolic activity. The patient also received immunotherapy with palbociclib and pembrolizumab.

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a) Pretreatment: lesion in the right occipital lobe (PTV1)

c) Post-treatment: lesion in the right occipital lobe (PTV1)

b) Pretreatment: lesions in the right hemi-pons (PTV2) and right temporal lobe (PTV3)

d) Post-treatment: lesions in the right hemi-pons (PTV2) and right temporal lobe (PTV3)

Figure 1. MRI scans of brain metastases fused with planning CT scan: pretreatment (upper images) and post-treatment (lower images)

An MRI scan of the brain (multiplanar sequences including post-gadolinium sequences), performed in October 2017, revealed an ovoid extra-axial, dural-based mass in the right occipital lobe, measuring 3.3 x 2.7 cm, associated with areas of internal susceptibility and surrounding edema (Figure 1a). The MRI also revealed a smaller enhancing dural nodule (0.7 x 0.6 cm) in the temporal lobe located in the floor of the right middle cranial fossa, with surrounding edema, and an intra-axial node (0.6 x 0.6 cm) in the right hemi-pons, with

surrounding edema (Figure 1b). Given the submitted diagnosis of osteosarcoma, these lesions were suspected brain metastases.

Clinically, the patient was experiencing occipital right-sided headache and subjective diplopia. Following a discussion about potential side effects, the patient agreed to stereotactic radiosurgery (SRS) to be delivered to the three targets in the brain in three fractions.

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Simulation and treatment planning

For simulation and setup, the patient was positioned supine with a knee support and his head was immobilized using Fraxion.

The prescribed dose and constraints were based on TG101 recommendations.1,2 Treatment planning was performed using Monaco version 5.11. A two millimeter GTV margin was added to each target, which is our normal practice for linac-based, frameless SRS. Each of the three targets was prescribed 25.5 Gy to be delivered in three fractions (based on the recommendations of Wiggenraad et al.3) every other day using a single isocenter, four VMAT arcs and a 6 MV FFF beam on a Versa HD linear accelerator (Table 1).

The isocenter was positioned closer to the smaller targets to reduce the risk of compromised PTV.4 For the calculation, a grid spacing of 0.2 cm was used and statistical uncertainty was set to 1.0 percent per calculation. The plan evaluation for the three brain metastases is shown in Table 2. Organs at risk (OAR) dose constraints and planned dose values are shown in Table 3. The total volume dose volume histogram (DVH) for the plan is shown in Figure 2, and isodose distributions for PTV1, PTV2 and PTV3 are shown in Figure 3.

Figure 2. Total volume DVH for the plan

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Table 1. Field details for each VMAT arc on Versa HD (6.0 MV FFF)

Direction Gantry Start (°) Arc (°) Increment (°) Collimator (°) Couch (°) MU/#

Arc 1 CW 180 360 20 0 0 1101.63

Arc 2 CCW 20 200 20 90 30 712.34

Arc 3 CW 180 140 20 90 90 889.35

Arc 4 CW 340 200 20 90 330 763.98

Table 2. Plan evaluation for three brain metastases

LocationPrescription Dose (Gy/3#)

PTV (cc)Dmax (Gy) <125% of TPD

PTV (%) = 25.5 Gy

PTV1 Right occipital lobe 25.50 27.536 31.178 99.89

PTV2 Right hemi-pons 25.50 0.829 31.455 100.00

PTV3 Right temporal lobe 25.50 1.255 30.422 100.00

Figure 3. Isodose distributions for PTV1, PTV2 and PTV3

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All plan objectives and dose constraints were met apart from the brainstem constraints. This was because PTV2 was located within the brainstem.

Table 3. OAR constraints and planned dose valuesOAR Constraints Plan (Gy/cc)

Brainstem18 Gy > 0.5 cc

2.10 cc (PTV2 located within brainstem)

MPD 23.1 Gy 26.965 Gy

Spinal Cord18 Gy < 0.35 cc 0

MPD 23.1 Gy 4.221 Gy

Optic Chiasm15.3 Gy > 0.2 cc 0

MPD 17.4 Gy 7.774 Gy

Right Optic Nerve15.3 Gy > 0.2 cc 0

MPD 17.4 Gy 5.707 Gy

Left Optic Nerve15.3 Gy > 0.2 cc 0

MPD 17.4 Gy 3.852 Gy

Normal Brain tissue (Brain-GTV)1 V18 < 30.2 cc 29.803 cc

Other OAR

Right Eye MPD < 8 Gy 5.219 Gy

Left Eye MPD < 8 Gy 3.139 Gy

Right Lens MPD < 8 Gy 3.323 Gy

Left Lens MPD < 8 Gy 1.951 Gy

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Treatment quality assurance (QA)Prior to the first treatment, the brain SRS plan check and QA check were performed using Mobius3DFX QA software and a 20-cm-slabs phantom with Gafchromic EBT3 film concurrently. Mobius3DFX has an independent beam model based on collapse cone dose calculation algorithm to check target coverage and OAR DVH limits. A dose grid of 2 mm and 3D gamma criteria of 3%/2 mm ≥ 95% were used.

Following these checks, triple channel film dosimetry analysis was performed with lateral response artifact correction. At this center, a pass rate of >95% was achieved with 2D gamma criteria of 2%/2 mm using FilmQAPro software and with 3D gamma criteria of 3%/2 mm using the Mobius3DFX software. Quality assurance using the Mobius3DFX software was also performed for the remaining fractions using log files.

Treatment delivery Treatment commenced on October 30, 2017, with the subsequent fractions delivered on November 1 and 3, 2017.

Prior to each fraction, an XVI VolumeView™ image was performed for isocentric and anatomical verification—with automatic bone registration completed, translation and rotational errors calculated and manual adjustments made as required. HexaPOD table shifts for each day are shown in Table 4.

Table 4. HexaPOD table shifts prior to treatment delivery

Translation (cm) Rotation (°)

Date X Y Z X Y Z

10.30.2017 -0.07 0.17 0.18 0.7 0.01 0

11.01.2017 -0.22 0.09 0.11 0.1 1.4 1.3

11.03.2017 -0.02 -0.02 0.14 0.7 0.2 0.4

Each fraction was delivered within a 15-minute timeslot. Total treatment time for each consecutive fraction was 12 minutes, 12 minutes and 14 minutes.

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Outcome and follow up A post-treatment brain MRI scan was performed on January 25, 2018, three months following the previous scan. The ovoid extra-axial, dural-based mass in the right occipital lobe could be seen, associated with areas of internal susceptibility and surrounding edema. Measuring 3.4 x 2.6 cm, this lesion appeared stable in size compared to the previous scan, with continued surrounding edema. However, there appeared to be decreased peripheral vascularity around this lesion (Figure 1c).

The smaller enhancing dural node in the right temporal lobe also appeared stable in size, measuring 0.7 x 0.6 cm, with decreased peripheral enhancement compared to the prior study. Similarly, the intra-axial node in the right hemi-pons, measuring 0.6 x 0.6 cm, appeared stable in size with decreased internal enhancement (Figure 1d).

Although there is little change in the size of these three brain metastases, the interval decrease in enhancement compared to the previous pretreatment MRI scan is suggestive of disease response.

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Discussion and conclusionFor frameless brain SRS/SRT, immobilization of the head with a stereotactic grade mask, such as Fraxion, is critical and enabled us to position the isocenter with minimal error. In our experience, the shifts required for longitudinal and pitch errors are the largest. This is likely due to sag on the treatment table and/or possible head tilt/motion. The use of a good IGRT workflow and the HexaPOD evo RT patient positioning system with submillimeter patient positioning accuracy enabled corrections to be made in six degrees of freedom—of particular value for the pitch error.

The use of Monaco—with the rapid and accurate Monte Carlo dose calculation algorithm—together with the high available modulation that can be achieved using Monaco and Agility™ (where the mechanism of the MLC leaves and the dynamic jaws produce a virtual leaf width of as little as 1 mm) allows highly accurate dose calculation, even for very small targets (~1.0 cc). These features eliminate the need for stereotactic cones or add-ons for treating single small targets.

A two-millimeter margin was used to account for factors such as potential patient movement in the mask, small targets or targets distant (> 4 cm) from

the isocenter. Furthermore, in a retrospective study, Choi et al. found that local control improved with a two-millimeter margin compared to no margin5.

For small field treatments delivering high doses per fraction, it is advantageous to use High Dose Rate delivery at some segments. Versa HD High Dose Rate (6 MV FFF) is able to deliver 1400 MU/min, which enables faster treatments and reduces the risk of intrafractional motion.

The combined accuracy of Monaco, Versa HD (with FFF) and HexaPOD, along with the use of a 2 mm GTV margin, enabled us to use a single isocenter, multi-focal SRS technique to treat multiple brain metastases as the primary option for this patient, instead of whole brain radiotherapy. This combination offers a much more versatile and efficient treatment compared to other brain SRS techniques, which are mainly designed for single or few targets, allowing all three targets to be treated within three standard 15-minute timeslots, with improved patient comfort and reduced risk of intrafraction patient movement.

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References

[1]  Minniti G, et al. Single-fraction versus multifraction (3 x 9 Gy) stereotactic radiosurgery for large (>2 cm) brain mets: a comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol Biol Phys. 2016;95(4):1142-48. doi: 10.1016/j.ijrobp.2016.03.013

[2]  Benedict SH, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37(8): 4078-101. doi: 10.1118/1.3438081

[3]  Wiggenraad R, et al. Dose–effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiother Oncol. 2011;98(3):292-7. doi:10.1016/j.radonc.2011.01.011

[4]  Roper J, et al. Single-isocenter multiple-target stereotactic radiosurgery: risk of compromised coverage. Int J Radiat Oncol Biol Phys. 2015;93(3):540-6. doi: 10.1016/j.ijrobp.2015.07.2262

[5]  Choi CY, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys. 2012;84(2):336-42. doi: 10.1016/j.ijrobp.2011.12.009

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