The use of a simultaneous integrated boost in spinal stereotactic body radiotherapy to reduce the risk of vertebral compression fractures: a treatment planning study

In the management of spinal metastases, stereotactic radiotherapy (SBRT) is an emerging technique intended to deliver a high-radiation dose precisely to the target [1]. Concern has been raised about the dose-fractionation schemes used in spinal SBRT as the risk of vertebral compression fractures (VCF) have been reported to be as high as 40% [2]. These rates are much higher compared to conventional radiotherapy, which is typically below 5% [3]. It was hypothesized that radiation effects in the form of bone and tumor necrosis compromise the ability of the vertebrae to withstand the axial loading forces, leading to an increased risk of VCF [4]. Clinicopathologic samples of spinal metastases, obtained after SBRT, showed radiation-induced tumor and osteonecrosis, giving evidence for this hypothesis [5,6]. More support for this hypothesis is provided by studies assessing VCF risk in patients receiving high-dose radiation for primary tumors in the thoracic or abdominal region, showing that vertebral fractures are mostly seen in the high-dose regions [7]. Prevention of VCF is challenging because the metastatic lesions lie within the segment at risk. A simultaneous integrated boost (SIB) dose delivery approach might mitigate the risk of SBRT-induced VCF by boosting the gross tumor volume (GTV) with the non-affected bone included in the clinical target volume (CTV). Currently, a SIB planning design has not been formally compared with a non-SIB approach. In this study, we report on the dosimetric feasibility of a SIB SBRT approach in the treatment of spinal metastases.

Study methods

Twelve patients with metastatic spinal disease without spinal cord compression were identified from the PRESENT cohort [8]. The cases were chosen in such a way that they form a representative selection of our stereotactically treated patient population (Supplementary Table S1 in the Supplementary material). Using CT and MR imaging, a radiation oncologist contoured the GTV, referred to as the boost (GTVb), the CTV, referred to as elective CTV (CTVe) (Supplementary Figure S1), and organs at risk (OAR). The GTVb was defined as the macroscopic extent of the spinal lesion that is demonstrable on imaging. The CTVe encompassed the bony compartment containing the GTVb [9]. Both the GTVb and the CTVe were expanded with a 2 mm margin (PTVb = GTVb + 2 mm; PTVe = CTVe + 2 mm). Volumetric arc therapy treatment (VMAT) plans were created using Monaco treatment planning system version 5.1 (Elekta, Stockholm, Sweden). The plans were designed for an Elekta Synergy linear accelerator (Elekta Inc., Crawley, UK). Two 10 MV photon beam posterior partial arcs with an average arc length of 115° were employed. The maximum number of control points per arc was set to 144, the minimum segment width to 0.5 cm, the collimator angle to 0°, and the Monte Carlo standard deviation per control point to 8%. The calculation grid resolution was 2 × 2×2 mm. For the SIB treatment plans, doses of 18 Gy to the PTVb and 8 Gy to the PTVe were prescribed in a single fraction. Treatment plans were optimized according to a priority list which guided the planning process in making compromises between competing constraints and objectives (Supplementary Table S2). In the non-SIB treatment approach, the entire PTVe was prescribed 18 Gy in a single fraction. These plans were optimized according to the priority list as well substituting PTVe to PTVb. For all treatment plans, 90% of the PTVb or PTVe had to receive at least 90% of the prescribed dose [10]. OAR were taken into account, with the spinal cord constraint being the most important one (Supplementary Tables S2 and S3). For each patient and planning modality, median values on target volume coverage and the Paddick conformity index (CI) [11] were calculated. The agreement between planned and delivered dose was assessed by a gamma analysis (3%, 2 mm gamma criterion with a 95% pass rate tolerance [12]). Paired data was evaluated using the non-parametric Wilcoxon signed-rank test, a p value <.05 defined statistical significance.

Results

For all cases, clinically acceptable and deliverable SIB and non-SIB treatment plan were obtained. For SIB SBRT plans, the coverage (V16.2Gy) of the PTVb was 95% which was significantly higher compared to the coverage of the PTVb in the non-SIB SBRT plans (92%) (Table 1). The median PTVe coverage of the non-SIB SBRT treatment plans was 81% (range 64–95%). In four of the SIB SBRT cases, the PTVb coverage was below 90% due to the proximity to the spinal cord (median shortest distance between tumor and spinal cord of 0.5 mm). In SIB SBRT plans, the median mean dose to the PTVe (minus PTVb) was 12 Gy, while this was 17 Gy for the non-SIB SBRT plans (p = .002). The largest difference between the two dose distributions was seen in Case 7 with a reduction of the PTVe mean dose of 8 Gy (Figure 1). The OAR constraints were easier to meet with the SIB SBRT approach with lower maximum doses to important surrounding tissues (Table 1). Nerve roots were better spared using the SIB technique with a reduction up to 7 Gy. The median delivery time of the non–SIB SBRT plans was 2 min longer than for the SIB plans (p = .013). Measured dose distributions showed excellent agreement with the calculated ones for all the plans, with on average 99% of the overall area within the region of interest fulfilling the acceptance criterion.

Figure 1. Delineation and planning for representative Case 7. (A) Axial planning’s CT slice showing the simultaneous integrated boost (SIB) SBRT dose distribution for a small metastasis in the L1 lumbar vertebral body. In this patient, the dose to the elective surrounding relatively healthy bone was effectively reduced from 18 to 11 Gy. (B) The non-SIB SBRT radiation treatment plan that this patient would have been given without the SIB SBRT approach.

Table 1. Dosimetric parameters for SIB and non-SIB treatment plans for single-dose spinal SBRT.

	SIB		Non-SIB
	Median	Range	Median	Range	p value
Target coverage
V16.2Gy PTVb (%)	95	81–100	92	75–100	.019
V16.2Gy PTVe (%)	39	6–61	81	64–95	<.01
V7.2Gy PTVe (%)	100	97–100	100	100–100	.043
Target dosimetry
D2% in PTVb (Gy)	21	19–24	–	–	–
D2% in PTVe (Gy)	–	–	20	20–23	–
D2% in (PTVe-PTVb) (Gy)	17	16–18	–	–	–
Dmean PTVb (Gy)	19	18–19	18	17–19	.015
Dmean PTVe (Gy)	15	11–17	18	16–18	<.01
Dmean (PTVe-PTVb) (Gy)	12	10–13	17	16–18	<.01
Conformity index^a PTVb	0.6	0.4–0.9	0.3	0–0.5	<.01
OAR evaluation^b
D1cc Spinal cord PRV (Gy)	8	6–9	10	8–10	.018
V10Gy Spinal cord (cc)	0	0–0.3	0.3	0.02–0.4	.018
D1cc Cauda equina (Gy)	11	8–13	12	12–13	.068
V13Gy Cauda equina (cc)	0.1	0–1	0.5	0.1–2	.138
D0.1cc Nerve roots (Gy)	14	9–18	17	16–18	.037
D1cc Bowel (cc)	9	5–14	11	5–14	.046
V11.2Gy Bowel (cc)	0.2	0–4	1	0–5	.114
D1cc Large vessels (Gy)	11	5–15	14	8–15	.012
V12Gy Large vessels (cc)	0.3	0–3	3	0–5	.012
D1cc Esophagus (Gy)	8	6–12	12	7–12	.080
V11.9Gy Esophagus (cc)	0	0–1	1	0–1	.273
Delivery time (s)	723	635–883	858	649–1326	.013
Monitor units	5757	4981–7244	6826	5072–10654	.013

D: dose; D2%: maximum dose in Gy to 2% of the volume; Dxcc: maximum dose in Gy to x cc of the volume; OAR: organ at risk; PTVb: planning treatment volume of the GTVb; PTVe: planning treatment volume of the CTVe; SIB: simultaneous integrated boost; V: volume; VxGy: volume in cc or percentages receiving at least x Gy.

^a The CI for the PTVb is calculated according to the formula of Paddick [11].

^b Based on treatment plans with target volume near OAR.

Discussion

This comparative planning study on single fraction SBRT evaluated the dosimetric feasibility of a SIB SBRT treatment planning approach for spinal metastases. Both SIB and non-SIB treatment designs resulted in clinically acceptable treatment plans. Despite not fulfilling the prescription dose in cases where the PTV was lying in close proximity of the spinal cord, the objective on the mean dose in the PTVb was always met assuring sufficient high dose to the metastasis itself. In the SIB SBRT treatment plans, the CTVe was better spared from the high dose prescribed to the spinal metastases and we showed that a dose reduction up to 8 Gy is achievable. Extrapolating the dose-response curve provided by Sahgal et al. [2], by sparing the relative healthy surrounding bone structures by on average 5.5 Gy, it allows reducing the number of VCF with 50% (from 10 to 5%). The use of a SIB SBRT approach is uncommon for spinal metastases. In the clinical study of Lubgan et al. [13], SIB plans for spinal SBRT were shown to be feasible while keeping the incidence of side effects low: they reported 1 VCF after 4 months in 33 patients. However, in their study the prescribed dose difference between PTVb and PTVe was 0.75 Gy per fraction with respect to the difference of 10 Gy of this work. At MD Anderson Cancer Center the SBRT planning protocol for spinal metastases includes a SIB technique for single fraction SBRT: 18–24 Gy is prescribed to the GTV, while the CTV receives 16 Gy [14]. Follow-up data from patients treated at MD Anderson Cancer Center showed a VCF in 32 out of 79 patients, still indicating high VCF rates after single-fraction SBRT with a SIB approach [15]. However, less than half of the included patients in this report actually received SIB SBRT. Moreover, an elective dose of 16 Gy the dose to the CTV is still relatively high. Finally, Mantel et al. [16] reported on safety of fractionated SBRT using a SIB concept in 26 out of a total of 36 patients. Seven patients (22%) developed progressive VCF, however, all vertebrae without a VCF prior to SBRT remained fracture-free. Beside the potential mitigated risk of SBRT-induced VCF, the SIB SBRT treatment planning approach has more possible advantages. With regard to the surrounding tissues, important OAR are better spared using a SIB SBRT strategy. Especially the dose to the spinal nerve roots is significantly lower in SIB SBRT plans possibly lowering the risk of radiculopathy [17]. Furthermore, the median delivery time of SIB plans was found to be 2 min shorter compared to the non-SIB plans. A shorter delivery time might result in less intrafraction motion and increase of patient comfort. Finally, we found that by optimizing the non-SIB SBRT treatment plans for PTVe coverage, the dose to the metastasis itself was lower compared to SIB SBRT plans. Therefore, also in non-SIB SBRT planning, the GTV should be considered as well during plan optimization. A limitation of our work could be the reproducibility of the study observations since treatment plans are operator dependent. In our department, however, treatment planning radiotherapists work with an priority list which results in more consistent plans with respect to target coverage and conformity [18]. Furthermore, we need follow-up data of patients who are treated with a SIB SBRT approach to confirm the hypothesis of less toxicity by sparing the surrounding relatively healthy bone. In conclusion, the required plan quality and accuracy in dose delivery can be achieved using a SIB SBRT treatment planning approach for spinal SBRT. Compared to non-SIB SBRT treatment plans, a substantial reduction of the dose to the relatively healthy bony compartment is achieved while guaranteeing a higher dose to the metastasis. This might mitigate the risk of radiation-induced vertebral fractures.

Acknowledgments

The authors would like to thank J.H.W. de Vries and J.G. Bijzet-Marsman for their valuable contribution to the implementation of stereotactic body radiotherapy for spinal metastases in our department.

Disclosure statement

A.S. has received honorarium for educational seminars from Medtronic and Elekta and research support from Elekta, has participated on the medical advisory board for Varian Medical Systems, and has received honoraria for past educational seminars from Accuray and Medtronic. The other authors report no conflicts of interest.