Comparison of treatment planning for stereotactic radiosurgery and stereotactic body radiation therapy techniques with 2.5mm and 5mm multileaf collimator (MLC): A pilot study

Introduction

Cancer is considered one of the leading causes of death worldwide, and its incidence and mortality rates may rise to approximately 29 million and 16 million people, respectively, by 2040. In India, the incidence rate of brain or nervous system-related cancers is the leading cause of death and is ranked 13th in males and 11th in females among all cancers.¹ Lung cancer is one of the most commonly diagnosed cancers and is considered to be the leading cause of death worldwide. It makes up 5.9% of all cancers and 8.1% of all cancer-related fatalities in India. It was found that smoking is one of the major reasons to cause lung cancer in 80% of the patients.^2,3 On average, approximately 20–54% of cancer patients will suffer from lung metastasis in their lifetime and almost 10–30% of all carcinoma patients have a risk of brain metastasis, which can originate from other primary sites.^4,5 Radiotherapy is an extremely cost-effective treatment modality, and almost 50% of cancer patients receive radiation therapy during their course of cancer treatment.⁶ In radiotherapy, high-energy photons such as X-rays, gamma radiation, or high-energy particles are used to deliver treatment externally using external beam radiation therapy (EBRT).⁷

Stereotactic radiosurgery (SRS) is a radiotherapy treatment technique in which a high radiation dose is delivered in a single fraction, using multiple radiation beams or arcs. If the same treatment is delivered in multiple fractions, it is called stereotactic radiotherapy (SRT).⁸ For selected intracranial lesions, SRS/SRT is performed as it delivers a high amount of radiation to the tumor volume, and the dose gradient is steep so that the surrounding uninvolved structures are spared.⁹ Lars Leksell, a Swedish neurosurgeon, initially introduced SRS in 1969 for treating intracranial lesions and has successfully shown positive results in managing intracranial lesions and brain metastasis and provided potential benefits in terms of good tumor control and reduced toxicity. It has increased the tumor control rate, survival rate, and quality of life. An SRS system based on a linear accelerator (LINAC) was developed in 1980, which allowed the treatment of SRS, SRT, and stereotactic body radiation therapy (SBRT) with high precision and accuracy.^10,11 Similar to SRS, SBRT is an SRT procedure that is used to treat extracranial lesions where hypofractionated radiation is administered in a fewer number of fractions. SBRT has been regularly incorporated as a better treatment option for metastatic and primary tumors such as lung cancer, liver lesions, and prostate cancer.¹²

Although surgery is the standard of care for patients with lung cancer who are healthy enough to undergo surgery, SBRT is considered to be one of the best therapeutic alternate options for inoperable patients.¹³ It was found that SBRT offers three-year local control in 70 to 90% of patients and two-year survival rate of 50 to 70% of patients.^14,15 For brain tumors less than 3cm, treatment with SRS given in a single fraction has shown the best results in the management of benign tumors, as it has various advantages such as a greater decrease in tumor size, sparing of normal tissues due to rapid dose fall-off, minimum radiation-related side effects, lesser duration of radiotherapy, and better tumor response. If the tumor size is greater than 3cm, SRS must be delivered in multiple fractions (SRT) so that normal tissue toxicity is minimized.^16,17

SRS/SRT/SBRT are complicated treatment procedures that include various steps such as patient immobilization and imaging with breath-hold techniques (specific to SBRT), treatment planning to avoid certain beam angulations especially when non-coplanar beams used, performing patient-specific quality assurance (QA) checks involving small volume ion chambers, and delivering radiation therapy to the patient with the attachment of additional small size multileaf collimator (if required in a particular setup like Elekta) to the LINAC head.¹⁸ As high radiation doses are delivered in a smaller fraction of treatments, and more suitable immobilization devices meant for SRS/SBRT are used to deliver radiation precisely to the tumor, very small error margins are given compared to conventional radiation therapy. A small error in the localization of the tumor, even in a single fraction, can lead to an underdosage of the tumor by 20% or more, and at the same time, it can overdose the surrounding normal tissues, thereby resulting in potentially serious injuries to the organs involved.¹⁹

The treatment delivery of stereotaxy has generally utilized dedicated specialized equipment such as Gamma Knife and CyberKnife. Medical LINACs have been increasingly adopted as a mode for delivering hypofractionated radiotherapy schedules. There are important advantages to using a LINAC for SRS/SRT/SBRT treatment, including increased versatility, cost benefits, and higher throughput. Technological advances have made use of LINAC and are increasingly accurate in stereotaxic treatment. One such device, designed to improve conformity to the target, is an externally attached additional collimating device with a micro-multileaf collimator (mMLC).²⁰ The mMLC has a high-resolution collimation system with a width of 2.5mm at the isocenter. This would facilitate the delivery of a conformal radiation dose to the tumor with a steep dose gradient beyond the tumor, thus better sparing the surrounding normal tissues. However, there is a disadvantage of reduced clearance between the patient and collimator, which limits the utilization of non-coplanar beam directions.²¹

Using the Elekta mMLC (Elekta, Sweden) known as apex for planning SRS/SRT/SBRT provides excellent dose distribution, but also offers technical errors in terms of mMLC and gantry calibration, correction of which adds to the total treatment duration. If the same plan with excellent output is available without the use of mMLC but with flattening filter-free (FFF) photon beam energies, then the treatment duration is expected to be reduced compared to Apex-based delivery.

This study aimed to compare SRS/SRT/SBRT treatment plans with and without the mMLC, using FFF radiation beams to compare the generated treatment plans in terms of various indices of planning target volume (PTV) coverage and organ-at-risk doses.

Methods

Contouring and treatment planning

The first plan for SRS/SBRT was developed using the dynamic conformal arc therapy (DCAT) technique with a 6FFF photon beam energy using a 2.5mm mMLC. The mMLC is an additional attachment to the collimator of the Elekta Versa high-definition LINAC consisting of an MLC with a 2.5mm width at the isocenter. This high-resolution collimating device is especially used for SRS treatment delivery to facilitate conformal dose distribution around the tumor. The maximum field size provided by the mMLC is 12 × 14cm².³⁶ The isocenter was placed at the center of the target volume. The number and direction of the arcs were chosen based on the location of the tumor. Couch movement was restricted in some cases, wherever it was practically impossible to move the gantry with the Apex to reduce the risk of collision of the gantry with the couch and patient. The second plan was generated without using mMLC. The LINAC has an inbuilt MLC with a 5mm width at the isocenter, which is also called Agility. The SRS/SBRT treatment plans in this case were performed with agility using a 6FFF photon beam energy. The treatment plan was implemented using the same gantry couch combinations. Multiple optimizations in both techniques were performed to achieve the prescribed tumor dose and to bring the dose to the OARs within the given limits. The Monte Carlo algorithm was used to calculate the dose distribution.³⁷ For the included cases, SRS was planned with 16Gy in one fraction ( Figure 1) and SBRT with 60 Gy in five fractions ( Figure 2). The dose was prescribed to the 80% isoline for the evaluation purpose.

Figure 1. Stereotactic radiosurgery (SRS) plan with APEX 2.5mm micro-multileaf collimator (mMLC) (left), SRS plan with Agility 5mm multileaf collimator (MLC) (right).

Red: 100% prescribed dose; Green: 95% prescribed dose; Blue: 50% prescribed dose; Yellow: 115% prescribed dose.

Figure 2. Stereotactic body radiation therapy (SBRT) plan with APEX 2.5mm micro-multileaf collimator (mMLC) (left), SBRT plan with Agility 5mm multileaf collimator (MLC) (right).

Red: 100% prescribed dose; Green: 95% prescribed dose; Blue: 50% prescribed dose; Blue (inside): 115% prescribed dose.

Results

The volume of the GTV and PTV in the selected brain targets were ranging between 0.6cm³ to 6.0cm³ and 1.2cm³ to 8.5cm³ respectively. Similarly, in the lung targets the GTV and PTV volumes were ranging between 4.3cm³ to 7cm³ and 8.5cm³ to 12.5cm³ respectively. Among the selected ten cases, 50% of the patients were treated at the metastatic sites, and in the remaining cases, treatments were administered at the primary sites. Both treatment planning techniques showed excellent tumor dose distribution and the PTV coverage was comparable in both treatment planning techniques. For brain SRS cases, the mean target coverage in 5mm MLC was 98.8±0.7, and in 2.5mm mMLC, it was 99.2±0.4(p=0.41) ( Figure 3). In lung SBRT cancers, the target coverage in 5mm MLC and 2.5mm mMLC was 97.9±2.0 and 99.1±1.2(p=0.30), respectively ( Figure 4), which shows that the APEX-based treatment plans showed slightly better target coverage, although both planning techniques provided a target coverage of more than 97%.

Figure 3. Planning target volume (PTV) coverage in the brain with 2.5mm and 5mm.

Figure 4. Planning target volume (PTV) coverage in the lung with 2.5mm and 5mm.

CI in both the SRS and SBRT plans was good in comparison. These values were found to be similar for both the planning techniques. In the 5mm and 2.5mm width MLC the mean CI for the brain targets were 0.9±0.01 and 0.9±0.04 respectively (p=0.80) and for the lung targets were 0.9±0.01 and 0.9±0.04 respectively (p=0.07) which indicates that the target area is optimally covered ( Figure 5) and there is no significant difference in the CI for brain and lung targets in both MLC designs. The HI values in case of 2.5mm and 5mm MLC in brain targets were 1.1±0.2 and 1.1±0.1 respectively (p=0.74) and for the lung targets the values were 1.1±0.1 and 1.1±0.1 respectively (p=0.78). The HI values were also found to be close to unity, indicating a homogenous dose distribution across the tumor volume ( Figure 6). The GI values for 5mm and 2.5mm MLC in brain targets were 5.1±0.4 and 4.3±1.0, respectively (p=0.15), and for the lung targets 4.6±1.3 and 4.5±1.1, respectively (p=0.89). Although there was no significant difference between the GI values, the obtained results showed that GI was better in the 2.5mm APEX based plans compared to 5mm MLC ( Figure 7). The mean and maximum doses to the OARs in both treatment planning techniques for both 2.5mm and 5mm MLC based plans were found to be close to each other. Although there was no significant difference between the two, it has been shown that the doses were slightly lower in most of the OARs in lung targets, whereas in brain targets, we received mixed results, indicating that both techniques are comparable ( Tables 1 and 2). Data on the same have been made available online.³⁹ The treatment duration was assessed by calculating the monitor units (MU) for the 2.5mm mMLC and 5mm MLC plans. It was found that the MU for brain targets with 2.5mm mMLC and 5mm MLC were 2482.6±75.8 and 5060.8±415.04 respectively and for lung targets the MU with 2.5mm mMLC and 5mm MLC were 1886.2±44.28 and 3646.1±506.7 respectively with p value less than 0.05. this indicates that the treatment duration with 2.5mm mMLC is longer compared to the 5mm MLC.

Figure 5. Conformity index (CI) in 2.5mm and 5mm multileaf collimator (MLC) for 10 cases (1-5 brain target, 6-10 lung target).

Figure 6. Conformity index (CI) in 2.5mm and 5mm multileaf collimator (MLC) for 10 cases (1-5 brain target, 6-10 lung target).

Figure 7. Gradient index (GI) in 2.5mm and 5mm multileaf collimator (MLC) for 10 cases (1-5 brain target, 6-10 lung target).

Discussion

In the current study, ABC was used for SBRT to manage the breathing of patients, and CBCT was used for verification. Accurate treatment was delivered to make sure that the setup error to be within the margin of ±1mm. Contouring of the brain and lung lesions was performed by the physicians after fusing the CT (Philips, 16 slice) images with MRI to draw accurate tumor volume and the OAR. CT is considered the first-line imaging modality used to diagnose the disease and to determine the true extent of the disease. However, the brain and mass in the lung are soft tissues, and the approximate and true spatial extent of the disease cannot be identified using CT images alone. MRI is superior to CT for the identification of soft tissues, definite tumor size, exact tumor location, number of lesions in the brain, and peritumoral edema. Therefore, both CT and MRI images were combined. The actual tumor volume was contoured on MRI and automatically mapped onto the CT image, which was then used for planning purposes.¹⁷

This study identified dosimetric differences in the treatment plans performed with the addition of 2.5mm mMLC and 5mm MLC. It is important to conform the radiation dose to the target volume in SRS/SRT/SBRT because of the size of the lesion and proximity of the OAR so that the dose distribution is bound tightly to the tumor volume. For this reason, dedicated machines are now available, including standard LINAC with added mMLC.⁴⁰ However, the addition of this device prolongs the total treatment duration and reduces the clearance between the collimator and patient because of restrictions in choosing the appropriate and required gantry angles most of the time. It has limitations in the placement of noncoplanar arc angles.⁴¹ The LINAC (Elekta HD Versa) used in the current study was equipped with a built-in 160 MLC with a width of 5mm at the isocenter. To deliver treatment plans performed with a 2.5mm MLC using the same LINAC, an additional collimating device (APEX) must be attached to the machine. APEX consists of 56 pairs of MLCs with a 2.5mm width at the isocenter, which provides a field size of 12 × 14cm².

The SRS and SBRT treatment plans performed with a 2.5mm MLC were considered as the benchmark in this study, and these plans were compared with a 5mm MLC. The plans with a 2.5mm MLC were optimized to deliver the best possible treatment with more than 95 to 98% coverage of the target volume with other parameters to be within the prescribed limits. In the plans with a 5mm MLC, the gantry, couch, and collimator combinations were kept constant, and the treatment plans were optimized to deliver the same dose distribution by keeping all the dose constraints to the OARs minimum. The resulting PTV coverage was equivalent in the 2.5mm and 5mm treatment plans. The obtained results were comparable to the results obtained by Wu et al., in which three planning techniques were used for the comparison, and the plans were performed using 2.5mm and 5mm MLC. They suggested that the PTV coverage, HI, and CI were better in IMRT-based HD MLC plans; however, as the size of the tumor increased and the OARs were closer to the target, the scope of HD MLC also became less noticeable.⁴¹

The treatment plan quality was compared using HI, CI, and GI.⁴² The HI and CI values for both the plans were comparable. Heather et al. conducted a study in which they compared MLC of three different widths, 2.5, 5, and 10mm, for the SBRT spine. With respect to tumor coverage, CI, and HI, the results of the study were comparable irrespective of leaf width.⁴³ Joablot et al. conducted a study wherein they performed SRS/SRT plans using 2.5mm, 5mm and 10mm MLC. With respect to HI, they found no clinically significant differences in any of the different MLC widths. In addition, there was no difference in the CI between 5mm and 2.5mm for PTV volumes greater than 1cc. However, for PTV volumes lesser than 1cc, the dose conformity was less in the 5mm MLC, but the amount of reduction was clinically acceptable. The OAR doses were found to be comparable irrespective of leaf width. The dose falloff was steep in the 2.5mm MLC which was clinically acceptable.²⁰ This result was also observed in the current study in terms of GI, which showed a steep dose fall off in the 2.5mm MLC. The GI was slightly higher in the 5mm MLC compared in the 2.5mm MLC which indicates a steeper dose fall in the 2.5mm MLC.⁴³ The GI is an important factor that indicates the surrounding normal tissue dose. The lesser the GI, the more the surrounding OARs are spared.⁴⁴ In a study conducted by Ferrer et al., three SRS cases were planned with a 5mm and 2.5mm MLC. They obtained similar results for conformation indices and OARs. The target coverage in VMAT is also better at the cost of more monitoring units. They found satisfactory results with VMAT, but in order to have more comparisons between VMAT and APEX, planning must be performed with a larger sample size.³⁹

In the current study, the plans with 2.5mm mMLC and 5mm MLC were limited to certain targets which are surrounded by less critical organs. However, it is important to highlight that a fairer comparison could have been made by considering targets located closer to the OARs. In these cases, the use of 2.5mm mMLC with finer leaf spacing is expected to demonstrate superior precision in beam shaping, thereby better sparing OARs compared to conventional 5mm MLC. Such a scenario would likely reveal the full potential of mMLC in minimizing radiation exposure to critical structures adjacent to the target. Including this factor in the study would provide a more comprehensive comparison of the 2.5mm mMLC and 5mm MLC, particularly in cases where the tumor is located near sensitive tissues. Future studies should aim to incorporate such cases to better assess the mMLC vs MLC.

This study adds to the literature by showing that a 5mm MLC may suffice in most cases of SRS and SBRT and will be beneficial in reducing the treatment time. This study was limited by the sample size and its retrospective nature.

Conclusions

There was no clinically significant difference found in the target coverage, CI, HI and OAR doses in ten patients planned for SRS and SBRT using 2.5mm mMLC (APEX) or 5mm MLC (agility) with 6FFF photon beam energy. The target coverage was comparable for both the plans. VMAT with agility provided equivalent tumor coverage with an additional number of MUs. The CI and HI values were almost similar in both plans, resulting in a conformal and homogenous dose distribution to the entire PTV. OAR doses were comparable in both MLC for brain cases, whereas for the lung targets, OAR doses were slightly lower with 2.5mm mMLC. GI was superor in the 2.5mm mMLC compared to the 5mm MLC giving a steep dose fall off in the dose distributions. Hence, a 5mm MLC is also preferred for SRS and SBRT, with GI being an important consideration during planning.