A Novel Technique to Validate Dosimetry for Single-Isocenter Multiple-Target VMAT Stereotactic Radiosurgery

Each year, 170,000 cancer patients in the United States develop brain metastases. Many of them present with multiple small lesions. Historically, Li-nac-based stereotactic radiosurgery (SRS) was used to treat single solitary brain metastasis with a diameter of less than 3.0 cm, while whole brain radiation therapy (WBRT) was used to treat multiple brain metastases mainly as palliative therapy. Evidence-based practices reveal that WBRT results in poor treatment outcomes, with high local recurrence rates, decreased cognitive function, and even the onset of dementia. Recently, volumetric modulated arc therapy (VMAT) SRS has been tested as an alternative treatment to WBRT. Owing to its inherent complexity and high risk, it is imperative to perform rigorous testing prior to its clinical implementation. In this paper, we present a novel technique for dosimetry validation of VMAT SRS.


Introduction
It is estimated that about 24% -45% of all American cancer patients have brain metastases [1]. As patients survive longer, multiple brain metastases are becoming more prevalent. One theory is that more effective systemic therapies may translate into an increase in brain metastases because chemotherapeutic agents do not penetrate the blood-brain barrier (BBB) [2]. These patients often present with subacute symptoms, such as headaches, nausea, vomiting, seizures, cogni- tive changes, motor dysfunction, and photophobia, depending on the location of metastases [3]. Currently, the most effective non-invasive treatment to relieve these symptoms is stereotactic radiosurgery (SRS) [4]. Traditionally, SRS has been used to treat solitary brain metastases. With the advent of volumetric modulated arc therapy (VMAT), there is growing interest in using VMAT SRS to treat multiple brain targets simultaneously with one single-isocenter plan [5]. This technique has several advantages over the conventional one target-one plan paradigm, including shortened treatment time and reduced integral dose to the normal brain tissue. However, the risk associated with VMAT SRS is also elevated if the precision of the delivery system and auxiliary imaging systems is compromised. One contributing factor to this risk is patient rotation-induced geometric misalignment between the actual treatment field aperture and planned field aperture. This arises from the fact that the isocenter of the delivery system can only be placed at one target center. The remaining targets, therefore, become off-isocenter. Dosimetric perturbation by geometric misalignment is negligible for the one target-one plan technique. This is because most brain metastases have a spherical shape, making them relatively immune to patient rotation in terms of delivered dosimetry. However, in the case of VMAT SRS, the magnitude of geometric misalignment is significantly amplified. It is roughly linearly proportional to the distance between the target center and the isocenter, the patient rotation angles, target distribution, and the target size and shape. Therefore, it is crucial to validate the delivered off-isocenter dosimetry for VMAT SRS prior to its clinical implementation. For this purpose, we have developed a novel, but the practical technique that can be easily reproduced in small community radiation oncology centers. In this paper, we present its detailed clinical implementation.

Dosimetry Verification Phantom
We used the commercial STEEV Stereotactic End-to-End Verification Phantom (CIRS, Norfolk, Virginia) for dosimetry validation. The STEEV phantom is made of tissue-equivalent materials. Their linear attenuation coefficients are within 1% of actual attenuation for soft tissue and bone. The STEEV phantom contains a 64 × 64 × 64 mm film insert in a rectangular brain cavity as shown in Figure 1. The cubic film insert has a 30-mm diameter build-in spherical target with +5% contrast. Thus, it appears much brighter than the surrounding material in CT scans. This feature greatly facilitates target delineation. A CIRS Precision Cut EBT3 film can be precisely positioned in the center plane of the target and locked by four pins. The pins prevent the film from moving and being misaligned with the insert edges. The film insert is assembled using four pinholes. The STEEV phantom has several external marks, making phantom setup quick, easy, and reproducible. Before inserting the film into the insert, the film should be marked with correct orientation so that the correct film orientation can be restored during film scanning and post-scanning analysis. Figure 1. The STEEV stereotactic end-to-end verification phantom. The phantom can be separated into two parts: the inferior part (left) and the superior part (right). The inferior part contains a film insert for dosimetry verification. The two parts can be assembled together by aligning the three pins in the inferior part with the pinholes in the superior part. The plan prescription dose was 1600 cGy, an optimal choice between the response characteristics of EBT3 film and a realistic clinical SRS dose. The volumetric dose calculation was performed with 6× photons using a special SRS small field beam model developed by our department. The prescription dose was normalized to 100% isodose line, a paradigm shift from the traditional 80% normalization methodology.   cm. The calibration film strips were exposed according to the pre-determined 7 dose levels. An unexposed film strip was reserved and used as zero dose exposure. In addition, one piece of film was delivered to 1600 cGy with a field size of 3.0 × 3.0 cm at the same depth for the purpose of calibration validation.

Film Dosimetry Measurement
The

Film Dosimetry Analysis
After a 24-hour color stabilization period, the exposed EBT3 film strips were scanned with a resolution of 450 dpi and initially processed with one-scan protocol using FilmQA Pro 2017. The choice of scanning resolution was crucial because 450 dpi provided target localization accuracy up to 0.056 mm. The dose maps were exported in TIFF format and then analyzed with our in-house film dosimetry analysis software. Figure 4 shows the planned (right) and measured film (left) dose distributions in the coronal plane, respectively. The red crosshair in the middle of the PTV1 dose distributions was the Linac isocenter. The grid resolution was 2.0 mm. As EBT3 films were very noisy in the high dose region, a 5 × 5 smoothing filter was applied to the dose maps in order to enhance the signal-to-noise ratio (SNR) of the data. Figure 5 is the overlay of the two dose distributions. The solid curve  represents the planned dose distribution and the dotted curve represents the measured film dose distribution. The two dose distributions reveal a high degree of dosimetric congruence, in particular, in the high dose region of clinical interest inside the targets. In the area outside the targets, as indicated by the 100% isodose line (cyan color), the two dose distributions still match quite well. Even in the area distant to the targets (near film edges), the geometric agreement between the two distributions is still within our institutional tolerance. The mean spatial separation between the two distributions is less than 1.0 mm, with the measured film dose distribution being slightly smaller at the lower isodose lines (lower than 40%). This is consistent with our past observations in film dosimetry measurements for single target SRS plans calculated with iPlan (BrainLab, Germany).  Figure 7 shows representative dose profiles for PTV2.

Results
In this case, PTV2 is 20 mm away from the Linac isocenter. Again, we observe an excellent agreement between the two profiles, even in the low dose regions at the film edges. Figure 8 shows the planned (right) and measured film (left) dose distributions in the sagittal plane, respectively. Figure 9 is the overlay of the two dose distributions. The sagittal plane demonstrates the same characteristics of dosimetric and geometric congruence as the coronal plane. Figure 10 shows representative dose profiles for PTV1 along the x-axis (left) and y-axis (right), respectively.

Discussion and Conclusions
Currently, the primary treatment options for patients with brain metastases include systemic therapy, surgery, stereotactic radiosurgery, WBRT, or some combination of these. For patients with multiple small lesions (≤20, <2.0 cm) or deeply seated lesions and poor performance status, the single-isocenter multiple-target VMAT SRS is an excellent treatment option. An increasing volume of clinical evidence suggests that multiple-target VMAT SRS offers significant benefits in both overall survival (OS) and quality of life (QOL) over conventional WBRT. However, the single-isocenter multiple-target VMAT SRS is a complex treatment modality. It requires that every part of the treatment hardware is tested and verified, including the treatment delivery system, auxiliary imaging systems, patient positioning system, and real-time patient tracking system. A carefully designed off-isocenter multiple target film dosimetry is the most critical component of this process.