- Email: [email protected]
Clinical Evaluation of Shot-Within-Shot Optimization for Gamma Knife Radiosurgery Planning and Delivery
Original Article
Clinical Evaluation of Shot-Within-Shot Optimization for Gamma Knife Radiosurgery Planning and Delivery Perry B. Johnson1, Maria I. Monterroso2, Fei Yang2, Elizabeth Bossart1, Amir Keyvanloo2, Eric A. Mellon2
OBJECTIVE: Shot-within-shot (SWS) optimization is a new planning technique that relies on various combinations of shot weighting and prescription isodose line (IDL) to reduce beam-on time. The method differs from other planning techniques that incorporate mixed collimation, multiple stereotactic coordinates, and traditionally low prescription IDLs (<60%). In this work, we evaluate the percentage of brain metastasis for which the method can be applied, the magnitude of the resultant time savings, and the possible tradeoffs in plan quality.
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METHODS: A retrospective analysis was performed on 75 patients treated for 241 metastatic lesions in the brain. For each lesion, the original planning metrics related to target coverage, conformity, gradient, and beam-on time were recorded. A subset of lesions were selected for replanning using the SWS technique based on size, shape, and proximity to critical structures. Two replans were done, a reference plan was prescribed at the 50% IDL, and an optimized plan was prescribed at an IDL typically >50%. Planning metrics were then compared among the original plan and the 2 replans.
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RESULTS: More than a third (39%) of the brain metastases were eligible for the SWS technique. For these lesions, the differences between the original plan and reference SWS plan were as follows: DV12Gy < 0.5 cc in
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Key words Gamma Knife - Gradient index - Metastases - Optimization - Radiosurgery - Shot-within-shot technique -
Abbreviations and Acronyms GI: Gradient index GK: Gamma Knife IDL: Isodose line SWS: Shot-within-shot SWS50%: New plan using the shot-within-shot technique prescribed at the 50% isodose line SWSopt: New plan using the shot-within-shot technique prescribed at the optimized isodose line
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93% of cases, DV12Gy < 0.5 cc in 100% of cases, Dselectivity < 0.1 in 79% of cases. Negligible differences were seen between the 2 replans in terms of Dselectivity and DV12Gy; DGI < 5% in 99% of cases. After optimization, beam-on time was reduced by 25%e30% in approximately 40%e50% of eligible lesions when compared with the reference SWS plan (DTmax [ 42%). In comparison with the original plan, beam-on time was reduced even further, DT > 50% in 20% of cases (DTmax [ 70%). CONCLUSIONS: This work demonstrates clinically that optimization using the shot-within-shot technique can reduce beam-on time without degrading treatment plan quality.
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INTRODUCTION
T
he shot-within-shot (SWS) technique is a planning method for Gamma Knife (GK) radiosurgery whereby 2 shots with different collimator sizes are assigned the same stereotactic coordinates. In previous work, we optimized SWS plans using 2 parameters: proportional shot weighting and prescription isodose line (IDL).1 It was shown that optimized SWS plans prescribed at higher IDLs (>50%) could achieve a similar conformity and gradient index as SWS plans prescribed at the
Vol: Volume V12Gy: Volume of normal brain receiving at least 12 Gy From 1Radiation Oncology/Biomedical Engineering and 2Radiation Oncology, University of Miami, Miami, Florida, USA To whom correspondence should be addressed: Perry B. Johnson, Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.140 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
SHOT-WITHIN-SHOT OPTIMIZATION FOR GK RADIOSURGERY
50% IDL while significantly reducing beam-on time. This is important for GK radiosurgery as treatments can be lengthy due to source decay, treatment of multiple lesions, and use of small collimation. In the United States, GK radiosurgery requires personal supervision by both an authorized user (radiation oncologist) and authorized medical physicist.2 Shorter treatments thus free up important resources while also improving throughput and providing a better experience for the patient. The extent of time reduction is dependent on lesion size and the degree to which the shape of the dose gradient is allowed to differ from a reference plan created using the SWS technique but prescribed at the 50% IDL. Modeling in a virtual phantom shows that there are 2 regions in lesion size that are candidates for optimization.1 Within these regions, beam-on time can be reduced by up to 40% when using 3% as a constraint on the differences in gradient indices between the optimized SWS plan and reference SWS plan. The only other expected change when using optimization is a lower maximum dose, which is proportional to the ratio of the optimized IDL and 50% IDL. The SWS technique is an alternative to other planning methods that may incorporate multiple shots having different stereotactic coordinates and potentially mixed collimation among the 8 sectors available on the GK Perfexion and Icon platforms (Elekta Instruments, Stockholm, Sweden). The difference between the techniques has not been previously quantified aside from a few test cases included in the prior study. It is theorized that the SWS technique may decrease conformity and beam-on time while having little effect on the volume of normal brain receiving an intermediate dose (e.g., volume of normal brain receiving 12 Gy [V12Gy], which is an important metric associated with symptomatic radiation necrosis).3,4 These tradeoffs have clinical implications that can only be evaluated once the relationship and magnitude of difference between the different factors is understood. This is particularly relevant for SWS optimization, which has yet to be fully validated in the clinical setting. In order to address these issues, we have performed a retrospective analysis of 75 patients treated for metastatic disease in the brain. For each case, the original planning metrics related to target coverage, conformity, gradient, and beam-on time were recorded. These metrics were then compared with those extracted from newly created plans using the SWS technique (when applicable) prescribed at both the 50% IDL and optimized IDL. As both the SWS technique and further optimization are not universally applicable, this study analyzes the percentage of brain metastasis for which these methods can be applied in practice, magnitude of the resultant time savings, and possible tradeoffs in plan quality. MATERIALS AND METHODS Initial Retrospective Review The GK experience at our institution dates to 2014 and includes a variety of treated conditions including brain metastasis, resection cavities, benign lesions, and functional targets. From this experience, all patients treated for brain metastasis between September 2014 and January 2016 were reviewed. This time span was chosen in order to select patients treated before the development of SWS
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Table 1. Description of Data Reviewed for Study Characteristic Number of patients
Value
Additional Information
75
Span ¼ 2.5 years
Number of metastases per patient x¼1
25
2x5
40
5 < x 10
7
x > 10 Total lesions
3
Max ¼ 15 mets
241
Choice of prescription IDL
Mean volume 4
Volmean ¼ 0.93 cc
50e59
158
Volmean ¼ 0.93 cc
60e69
39
Volmean ¼ 0.07 cc
70e79
32
Volmean ¼ 0.06 cc
>80
8
Volmean ¼ 0.03 cc
<50
Excluded from SWS technique
148
x > 16 mm collimator
25
x < 4 mm collimator
92
Irregular/adjacent/ DV12Gy>1cc
31
Included for SWS technique
93
Original plan used mixed collimation
74
Original plan used multiple coordinates
43
Original plan used either mixed collimation or multiple coordinates
63
Original plan prescribed at IDL >50%
17
Utilization ¼ 39%
IDL, isodose line; SWS, shot-within-shot.
optimization. The cases represent conventional planning techniques primarily using low-prescription IDLs (<60%), composite sector blocking, and, at times, multiple shots having different stereotactic coordinates. After obtaining Institutional Review Board approval, the following data were extracted separately from each target grid (note that many patients had multiple targets): target volume, prescription dose, prescription IDL, planning technique, target coverage, selectivity, gradient index (GI), V12Gy, and beam-on time. New Plans Created Using SWS Technique Each target was considered for replanning using the SWS technique. Targets were excluded on the basis of 4 conditions: 1) if the entire lesion could not be encompassed by the largest collimator setting available on the GK Perfexion (16 mm) when prescribed at
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
the 50% IDL, 2) if the entire lesion could be encompassed by the smallest collimator setting on the GK Perfexion (4 mm) when prescribed at the 50% IDL, 3) if the lesion was directly adjacent to another lesion or critical structure such as the brainstem or optic apparatus, or 4) if the lesion was noted as having a highly irregular shape. For the remaining lesions, 2 new plans were created using the SWS technique: a reference plan prescribed at the 50% IDL (SWS50%) and an optimized plan prescribed at a variable IDL (SWSopt). The reasoning behind the reference plan was to use the SWS technique in a way that conforms to standard practice and guarantees an acceptable dose fall-off. For the reference plan, the collimator weighting was set so as to achieve the same target coverage as the original plan. For the optimized plan, the prescription IDL and collimator weighting were selected using an optimization table developed in prior work.1 Using this table, optimization is predicted to achieve the same target coverage as the reference plan while maintaining a dose gradient that differs by no more than 3%. As with the original plans, the same plan evaluation metrics were recorded for each new plan: coverage, selectivity, GI, V12Gy, and beam-on time. Determination of Utilization Rate and Efficacy Once the 2 new plans were created, targets were additionally excluded (fifth criteria) if the difference in V12Gy between the original plan and either of the new plans was >1 cc. The utilization rate of the SWS technique was then determined by taking the ratio of the remaining lesions to the total number of lesions. The
Figure 1. Scatter plot highlighting how changes in conformity (Dselectivity) affect the difference in volume of normal brain receiving 12 Gy (DV12Gy). The comparison is between the original plan and the reference plan, which is prescribed at the 50% isodose
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efficacy of SWS optimization was assessed cumulatively by looking at the percentage of targets that achieved a specified reduction in beam-on time (10%, 20%, etc.) in comparison with the original plan and the reference plan using the SWS technique. RESULTS A total of 241 sequentially treated brain metastasis were reviewed. The number of metastases per patient, original choice of prescription IDL, and planning technique are summarized in Table 1. The results show that the majority of lesions were originally prescribed to an IDL representing <60% of the maximum dose. In addition, the mean volume of lesions prescribed at higher IDLs was significantly less than those prescribed at low IDLs. This highlights the fact that before SWS optimization, higher prescription IDLs were reserved in our practice only for very small lesions to increase selectivity (improve conformity) when the 50% IDL significantly exceeded the target boundary. A total of 148 brain metastases were excluded according to the criteria set out in the earlier sections. The majority of these lesions (92/148) were small and could be encompassed within a single 4-mm shot. Although many irregularly shaped lesions were excluded before replanning, 8 lesions were excluded post planning due to large differences in V12Gy (>1 cc). These lesions were later identified as having an ellipsoidal as opposed to irregular shape. The mean difference in these cases between the selectivity of the original plan and the selectivity of the SWS50% plan was 0.24 as compared with 0.01 for all other lesions. This alludes to the importance of conformity and its role in minimizing the
line (IDL) using the shot-within-shot technique. The correlation indicates that as the prescription IDL becomes less conformal, there is the potential for intermediate IDLs to gradually expand.
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SHOT-WITHIN-SHOT OPTIMIZATION FOR GK RADIOSURGERY
Figure 2. Axial (top), sagittal (middle), and coronal (bottom) images showing the isodose lines of a lesion that was excluded after replanning on the basis of large differences in V12Gy. Column A shows the original plan
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and column B shows the optimized plan. Note how the elongated shape of the lesion necessitates multiple shots using different stereotactic coordinates in order to improve conformity.
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
Figure 3. Axial (top), sagittal (middle), and coronal (bottom) images showing the isodose lines of a lesion that was optimized efficiently using the shot-within-shot technique. Column A shows the original plan prescribed at the 50% IDL, and column B
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shows the optimized plan prescribed at the 62% isodose line. The difference in beam-on time was 22% with all other metrics being relatively equal except for the maximum dose within the target.
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SHOT-WITHIN-SHOT OPTIMIZATION FOR GK RADIOSURGERY
Figure 4. Histogram highlighting the percent difference in gradient index when changing from a reference
intermediate dose in certain cases. Figure 1 shows the correlation between Dselectivity and DV12Gy for all cases in which a new plan was created (D ¼ Original e SWS50%). The correlation coefficient for this comparison was 0.75 (P ¼ 0.0012 using 2-tailed T-test). The correlation coefficient between volume and DV12Gy was 0.36 (P ¼ 7 1013) and between DGI and DV12Gy was 0.04 (P ¼ 6 106). The number of remaining lesions with DV12Gy <1 cc was 93. In addition, 86 lesions were found to have a DV12Gy <0.5 cc. Counting all exclusions, the percentage of lesions that could be effectively treated with the SWS technique (utilization rate) was calculated at 39%. Figure 2 shows axial, sagittal, and coronal isodose lines of the original and optimized plans for an excluded case (oblong lesion). Figure 3 shows the same information for an eligible case. In comparing the dose fall-off between the optimized and reference plans, Figure 4 highlights the percent difference in GI between the 2 datasets. On the basis of this histogram, it can be seen that in only one instance did the GI worsen by >5%. In addition, a total of 67 plans (72%) had a GI no worse than 3%. These numbers are relevant considering the optimization method was designed to ensure a similar dose fall-off to a plan prescribed at the 50% IDL using the SWS technique. The efficacy of SWS optimization is highlighted in Figure 5A and B. The top figure includes data on all 93 lesions for which new plans were created. The bottom figure excludes 17 lesions, which were originally prescribed at IDLs >50%. In a few of
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shot-within-shot (SWS) plan to an optimized SWS plan. All 93 eligible lesions were included in the comparison.
these cases, the beam-on time increased when applying the SWS technique. This resulted in the crossing of the solid and dotted lines seen in Figure 5A, where the lines themselves represent the difference in beam-on time when comparing the optimized plans with both the original and reference SWS plans. In the bottom figure, the optimized plan is always being compared with a plan prescribed at the 50% IDL, either the original or reference SWS plan. As a result, beam-on time never increases when plans are optimized. The area between the solid and dotted lines of Figure 5A and B indicates that beam-on time is reduced in many cases simply by applying the SWS technique. Additional reductions are then achieved by adding IDL optimization. In looking specifically at the histograms, which assess the time reduction between the 2 new plans (dotted lines), the extent of the curves matches expectations based on prior work. Here, the assumption was a maximum time reduction of roughly 40%, which was indeed seen in the current data. Simulations also previously demonstrated that IDL optimization would be most effective for targets that fell within 2 distance size ranges. Figure 6A plots DT (D ¼ SWS50% e SWSopt) as a function of effective target diameter calculated on the basis of an equivalent spherical volume. Figure 6B plots similar information as predicted on the basis of phantom studies. In comparing the 2 figures, the centers of the twin peaks are shifted, possibly due to the assumption of spherical shape in calculating an effective
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
Figure 5. Cumulative histograms showing the reduction in beam-on time as a percentage of the total number of lesions included in the analysis. The top figure (A) includes all 93 eligible lesions. The bottom figure (B) excludes 17 lesions from the analysis for which the
diameter (i.e., true diameter effective diameter). The overall shapes and magnitudes, however, are consistent. The approximate size ranges associated with the 2 peaks in Figure 6A are 0.05e0.3 cc and 1.1e2.1 cc, respectively, when calculated using an equivalent spherical volume.
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original plan was prescribed at an isodose line >50%. The solid line represents the time difference between the optimized SWS plan and the original plan. The dotted line represents the time difference between the optimized SWS plan and the reference SWS plan.
DISCUSSION The results of this study indicate that almost 40% of otherwise unselected brain metastasis at our institution would be eligible for GK planning using the SWS technique with resultant reductions in treatment time. In practice, it is fairly easy to determine eligibility
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
SHOT-WITHIN-SHOT OPTIMIZATION FOR GK RADIOSURGERY
Figure 6. Histograms showing the reduction in beam-on time as a function of lesion diameter. The time difference is calculated between the optimized SWS plan and the reference SWS plan. The top figure (A) represents data as measured in the current study,
on the basis of lesion size, shape, and proximity to critical structures. Once a target has been deemed eligible, a reference plan can be created using the SWS technique prescribed at the 50% IDL. According to this study, the reference plan will in the majority of cases reduce beam-on time in comparison with other planning techniques that incorporate mixed collimation and/or multiple stereotactic coordinates. Once a reference plan is created, optimization of the prescription IDL and shot weighting should further reduce beam-on time for most cases. The amount of time reduction can be estimated (Figure 6). The trade-offs associated with these methods can be thought of in terms of intermediate dose, high dose, and maximum dose. In regards to intermediate dose, the current results show differences in V12Gy to be minimal (<0.5 cc in most cases), partly due to the maintenance of a steep dose gradient and partly due to the fact
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which includes 93 lesions. The bottom figure (B) represents the predicted relationship between DT and lesion diameter on the basis of phantom studies. The shape and magnitude of the distributions are similar, though there is a clear shift in the x-axis.
that eligible lesions are inherently small (Volmean ¼ 0.4 cc, Volmax ¼ 2.2 cc). A number of studies have stratified the risk of radiation necrosis based on V12Gy at increments of 5 cc (V12Gy > 0e 5 cc, 5e10 cc, etc.).2,3 It is left to the practitioner to decide for a given patient whether any marginal increase in V12Gy is relevant on the basis of such studies. In regards to high dose, most lesions showed only small differences in the conformity of the prescription dose to the target volume (Dselectivity <0.1 for 73/93 lesions). There were a few instances, however, in which this proved not to be the case (Dselectivity >0.2 for 5 lesions, max ¼ 0.3). Whether this is consequential likely depends on the location of the target to critical structures and eloquent regions of the brain parenchyma. In clinical practice, exclusions should be made on a case-by-case basis. Although multiple studies have shown no correlation between decreasing conformity and
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
Figure 7. Histograms showing the number of cases for which a specific IDL was prescribed. The top figure represents the original choice of prescription IDL, and the bottom figure represents the prescription IDL after
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SWS optimization. The dotted line represents the inverse relationship between prescription IDL and maximum dose.
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ORIGINAL ARTICLE PERRY B. JOHNSON ET AL.
SHOT-WITHIN-SHOT OPTIMIZATION FOR GK RADIOSURGERY
increasing symptomatic radiation necrosis,5-8 this study did observe a correlation between changes in conformity and V12Gy. As the prescription IDL becomes less conformal, there is the potential for intermediate and low IDLs to gradually expand (see Figures 1 and 2). This may lead to an increase in V12Gy without a significant change in the GI. Thus even though the SWS technique is efficient at maintaining a steep dose gradient, conformity and its effect on intermediate dose may become a limiting factor if applying the method toward an ellipsoidal or irregularly shaped target. For lesions where this may be an issue, it is prudent to try other techniques in addition to the SWS method and then compare plans using DVH metrics. The correlation between conformity and V12Gy is an interesting (albeit intuitive) finding that applies broadly to GK planning. Finally, as with all GK plans, the prescription IDL is inversely correlated with maximum dose. Figure 7 highlights this relationship along with illustrating how the distribution of prescription IDLs in this study changed once optimization was included. While such a modification may seem drastic, it is important to keep in mind that both standard linear accelerator (LINAC) and robotic radiosurgery are commonly prescribed in the 65%90% IDL range without clear evidence of worse outcomes.9-11 Indeed, a number of recent studies have found no correlation between prescription IDL and local control/radiation necrosis7,12 or, more interestingly, that higher-prescription IDLs are positively correlated with local control.8,13 The working hypothesis for the latter result has to do with the broad penumbra traditionally associated with higher-prescription IDLs. For cases in which no prior margin exists, a broad penumbra mitigates the
1. Johnson P, Monterroso M, Yang F, Mellon E. Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique. Radiat Oncol. 2017;12, 187, 1-9. 2. Nuclear Regulatory Commission. Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units, 10 CFR 35.615. 2015. 3. Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy Gamma Knife radiosurgical volume is a predictor for radiation necrosis in non-avm intracranial tumors. Int J Radiat Oncol Biol Phys. 2006;64:419-424. 4. Lawrence Y, Li X, el Naqa I, et al. Radiation dosevolume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76:S20-S27. Kondziolka D, Pollock BE, et al. from arteriovenous malformation multivariate analysis and risk J Radiat Oncol Biol Phys. 1997;38:
6. Nakamura JL, Verhey LJ, Smith V, et al. Dose conformity of Gamma Knife radiosurgery and risk
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CONCLUSIONS In this work, both the utilization rate and efficacy of SWS optimization were assessed by replanning a cohort of 75 patients. The results showed that 39% of brain metastases were eligible for replanning. Excluded lesions included those larger than the 16-mm collimator, smaller than the 4-mm collimator, ellipsoidal or irregular in shape, or near critical structures. For the remaining subset, beam-on time was reduced through implementation of the SWS technique and then extended further through optimization of the prescription IDL and shot weighting. Time reductions on the order of 25%e30% were seen in approximately 40%e50% of eligible lesions. Only small differences were noted in the gradient index, conformity, and V12Gy for most cases in comparison with the original treatment plan.
factors for complications. Int J Radiat Biol Phys. 2003;81:115-119.
REFERENCES
5. Flickinger JC, Complications radiosurgery: modeling. Int 489-490.
effects of procedural uncertainty and potentially treats microscopic disease, which may extend beyond the visible tumor boundary. Although the penumbra was purposely kept sharp in the current study, the control afforded through optimization enables the creation of a variety of beam profiles and penumbra. Future work will further explore this option while investigating how such plans compare with those initially created with a margin, being mindful always of the effect on intermediate dose and potential for radiation necrosis. The expectation when using SWS optimization in the current form, however, is that neither local control nor radiation necrosis will be any worse than plans prescribed at the 50% IDL based on similar target coverage and levels of V12Gy.
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7. Shiue K, Barnett G, Suh J, et al. Using higher isodose lines for Gamma Knife treatment of 1 to 3 brain metastases is safe and effective. Neurosurgery. 2014;74:360-366. 8. Romano K, Trifiletti D, Garda A, et al. Choosing a prescription isodose in stereotactic radiosurgery for brain metastases: implications for local control. World Neurosurg. 2017;98:761-767. 9. Meeks S, Buatti J, Bova F, et al. Treatment planning optimization for linear accelerator radiosurgery. Int J Radiat Oncol Biol Phys. 1998;41: 183-197.
12. Jani A, Rozenblat T, Nanda T, et al. The energy index does not affect local control of brain metastases treated by Gamma Knife stereotactic radiosurgery. Neurosurgery. 2015;77:119-125. 13. Sharma M, Jia X, Ahluwalia M, et al. First followup radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastasis. Cancer Med. 2017;6:2076-2086.
Conflict of interest statement: The authors did not receive specific funding for this study. All data collection and analysis was performed as part of the routine clinical practice at the academic facility. The authors have no competing interest to disclose.
10. Sio T, Jang S, Lee SW, et al. Comparing Gamma Knife and Cyberknife in patients with brain metastases. J App Clin Med Phys. 2014;15:14-26.
Received 12 September 2018; accepted 16 November 2018
11. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363: 1665-1672.
Journal homepage: www.journals.elsevier.com/worldneurosurgery
Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.140
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.140
Clinical Evaluation of Shot-Within-Shot Optimization for Gamma Knife Radiosurgery Planning and Delivery Perry B. Johnson1, Maria I. Monterroso2, Fei Yang2, Elizabeth Bossart1, Amir Keyvanloo2, Eric A. Mellon2
OBJECTIVE: Shot-within-shot (SWS) optimization is a new planning technique that relies on various combinations of shot weighting and prescription isodose line (IDL) to reduce beam-on time. The method differs from other planning techniques that incorporate mixed collimation, multiple stereotactic coordinates, and traditionally low prescription IDLs (<60%). In this work, we evaluate the percentage of brain metastasis for which the method can be applied, the magnitude of the resultant time savings, and the possible tradeoffs in plan quality.
-
METHODS: A retrospective analysis was performed on 75 patients treated for 241 metastatic lesions in the brain. For each lesion, the original planning metrics related to target coverage, conformity, gradient, and beam-on time were recorded. A subset of lesions were selected for replanning using the SWS technique based on size, shape, and proximity to critical structures. Two replans were done, a reference plan was prescribed at the 50% IDL, and an optimized plan was prescribed at an IDL typically >50%. Planning metrics were then compared among the original plan and the 2 replans.
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RESULTS: More than a third (39%) of the brain metastases were eligible for the SWS technique. For these lesions, the differences between the original plan and reference SWS plan were as follows: DV12Gy < 0.5 cc in
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Key words Gamma Knife - Gradient index - Metastases - Optimization - Radiosurgery - Shot-within-shot technique -
Abbreviations and Acronyms GI: Gradient index GK: Gamma Knife IDL: Isodose line SWS: Shot-within-shot SWS50%: New plan using the shot-within-shot technique prescribed at the 50% isodose line SWSopt: New plan using the shot-within-shot technique prescribed at the optimized isodose line
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93% of cases, DV12Gy < 0.5 cc in 100% of cases, Dselectivity < 0.1 in 79% of cases. Negligible differences were seen between the 2 replans in terms of Dselectivity and DV12Gy; DGI < 5% in 99% of cases. After optimization, beam-on time was reduced by 25%e30% in approximately 40%e50% of eligible lesions when compared with the reference SWS plan (DTmax [ 42%). In comparison with the original plan, beam-on time was reduced even further, DT > 50% in 20% of cases (DTmax [ 70%). CONCLUSIONS: This work demonstrates clinically that optimization using the shot-within-shot technique can reduce beam-on time without degrading treatment plan quality.
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INTRODUCTION
T
he shot-within-shot (SWS) technique is a planning method for Gamma Knife (GK) radiosurgery whereby 2 shots with different collimator sizes are assigned the same stereotactic coordinates. In previous work, we optimized SWS plans using 2 parameters: proportional shot weighting and prescription isodose line (IDL).1 It was shown that optimized SWS plans prescribed at higher IDLs (>50%) could achieve a similar conformity and gradient index as SWS plans prescribed at the
Vol: Volume V12Gy: Volume of normal brain receiving at least 12 Gy From 1Radiation Oncology/Biomedical Engineering and 2Radiation Oncology, University of Miami, Miami, Florida, USA To whom correspondence should be addressed: Perry B. Johnson, Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.140 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
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50% IDL while significantly reducing beam-on time. This is important for GK radiosurgery as treatments can be lengthy due to source decay, treatment of multiple lesions, and use of small collimation. In the United States, GK radiosurgery requires personal supervision by both an authorized user (radiation oncologist) and authorized medical physicist.2 Shorter treatments thus free up important resources while also improving throughput and providing a better experience for the patient. The extent of time reduction is dependent on lesion size and the degree to which the shape of the dose gradient is allowed to differ from a reference plan created using the SWS technique but prescribed at the 50% IDL. Modeling in a virtual phantom shows that there are 2 regions in lesion size that are candidates for optimization.1 Within these regions, beam-on time can be reduced by up to 40% when using 3% as a constraint on the differences in gradient indices between the optimized SWS plan and reference SWS plan. The only other expected change when using optimization is a lower maximum dose, which is proportional to the ratio of the optimized IDL and 50% IDL. The SWS technique is an alternative to other planning methods that may incorporate multiple shots having different stereotactic coordinates and potentially mixed collimation among the 8 sectors available on the GK Perfexion and Icon platforms (Elekta Instruments, Stockholm, Sweden). The difference between the techniques has not been previously quantified aside from a few test cases included in the prior study. It is theorized that the SWS technique may decrease conformity and beam-on time while having little effect on the volume of normal brain receiving an intermediate dose (e.g., volume of normal brain receiving 12 Gy [V12Gy], which is an important metric associated with symptomatic radiation necrosis).3,4 These tradeoffs have clinical implications that can only be evaluated once the relationship and magnitude of difference between the different factors is understood. This is particularly relevant for SWS optimization, which has yet to be fully validated in the clinical setting. In order to address these issues, we have performed a retrospective analysis of 75 patients treated for metastatic disease in the brain. For each case, the original planning metrics related to target coverage, conformity, gradient, and beam-on time were recorded. These metrics were then compared with those extracted from newly created plans using the SWS technique (when applicable) prescribed at both the 50% IDL and optimized IDL. As both the SWS technique and further optimization are not universally applicable, this study analyzes the percentage of brain metastasis for which these methods can be applied in practice, magnitude of the resultant time savings, and possible tradeoffs in plan quality. MATERIALS AND METHODS Initial Retrospective Review The GK experience at our institution dates to 2014 and includes a variety of treated conditions including brain metastasis, resection cavities, benign lesions, and functional targets. From this experience, all patients treated for brain metastasis between September 2014 and January 2016 were reviewed. This time span was chosen in order to select patients treated before the development of SWS
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Table 1. Description of Data Reviewed for Study Characteristic Number of patients
Value
Additional Information
75
Span ¼ 2.5 years
Number of metastases per patient x¼1
25
2x5
40
5 < x 10
7
x > 10 Total lesions
3
Max ¼ 15 mets
241
Choice of prescription IDL
Mean volume 4
Volmean ¼ 0.93 cc
50e59
158
Volmean ¼ 0.93 cc
60e69
39
Volmean ¼ 0.07 cc
70e79
32
Volmean ¼ 0.06 cc
>80
8
Volmean ¼ 0.03 cc
<50
Excluded from SWS technique
148
x > 16 mm collimator
25
x < 4 mm collimator
92
Irregular/adjacent/ DV12Gy>1cc
31
Included for SWS technique
93
Original plan used mixed collimation
74
Original plan used multiple coordinates
43
Original plan used either mixed collimation or multiple coordinates
63
Original plan prescribed at IDL >50%
17
Utilization ¼ 39%
IDL, isodose line; SWS, shot-within-shot.
optimization. The cases represent conventional planning techniques primarily using low-prescription IDLs (<60%), composite sector blocking, and, at times, multiple shots having different stereotactic coordinates. After obtaining Institutional Review Board approval, the following data were extracted separately from each target grid (note that many patients had multiple targets): target volume, prescription dose, prescription IDL, planning technique, target coverage, selectivity, gradient index (GI), V12Gy, and beam-on time. New Plans Created Using SWS Technique Each target was considered for replanning using the SWS technique. Targets were excluded on the basis of 4 conditions: 1) if the entire lesion could not be encompassed by the largest collimator setting available on the GK Perfexion (16 mm) when prescribed at
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the 50% IDL, 2) if the entire lesion could be encompassed by the smallest collimator setting on the GK Perfexion (4 mm) when prescribed at the 50% IDL, 3) if the lesion was directly adjacent to another lesion or critical structure such as the brainstem or optic apparatus, or 4) if the lesion was noted as having a highly irregular shape. For the remaining lesions, 2 new plans were created using the SWS technique: a reference plan prescribed at the 50% IDL (SWS50%) and an optimized plan prescribed at a variable IDL (SWSopt). The reasoning behind the reference plan was to use the SWS technique in a way that conforms to standard practice and guarantees an acceptable dose fall-off. For the reference plan, the collimator weighting was set so as to achieve the same target coverage as the original plan. For the optimized plan, the prescription IDL and collimator weighting were selected using an optimization table developed in prior work.1 Using this table, optimization is predicted to achieve the same target coverage as the reference plan while maintaining a dose gradient that differs by no more than 3%. As with the original plans, the same plan evaluation metrics were recorded for each new plan: coverage, selectivity, GI, V12Gy, and beam-on time. Determination of Utilization Rate and Efficacy Once the 2 new plans were created, targets were additionally excluded (fifth criteria) if the difference in V12Gy between the original plan and either of the new plans was >1 cc. The utilization rate of the SWS technique was then determined by taking the ratio of the remaining lesions to the total number of lesions. The
Figure 1. Scatter plot highlighting how changes in conformity (Dselectivity) affect the difference in volume of normal brain receiving 12 Gy (DV12Gy). The comparison is between the original plan and the reference plan, which is prescribed at the 50% isodose
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efficacy of SWS optimization was assessed cumulatively by looking at the percentage of targets that achieved a specified reduction in beam-on time (10%, 20%, etc.) in comparison with the original plan and the reference plan using the SWS technique. RESULTS A total of 241 sequentially treated brain metastasis were reviewed. The number of metastases per patient, original choice of prescription IDL, and planning technique are summarized in Table 1. The results show that the majority of lesions were originally prescribed to an IDL representing <60% of the maximum dose. In addition, the mean volume of lesions prescribed at higher IDLs was significantly less than those prescribed at low IDLs. This highlights the fact that before SWS optimization, higher prescription IDLs were reserved in our practice only for very small lesions to increase selectivity (improve conformity) when the 50% IDL significantly exceeded the target boundary. A total of 148 brain metastases were excluded according to the criteria set out in the earlier sections. The majority of these lesions (92/148) were small and could be encompassed within a single 4-mm shot. Although many irregularly shaped lesions were excluded before replanning, 8 lesions were excluded post planning due to large differences in V12Gy (>1 cc). These lesions were later identified as having an ellipsoidal as opposed to irregular shape. The mean difference in these cases between the selectivity of the original plan and the selectivity of the SWS50% plan was 0.24 as compared with 0.01 for all other lesions. This alludes to the importance of conformity and its role in minimizing the
line (IDL) using the shot-within-shot technique. The correlation indicates that as the prescription IDL becomes less conformal, there is the potential for intermediate IDLs to gradually expand.
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Figure 2. Axial (top), sagittal (middle), and coronal (bottom) images showing the isodose lines of a lesion that was excluded after replanning on the basis of large differences in V12Gy. Column A shows the original plan
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and column B shows the optimized plan. Note how the elongated shape of the lesion necessitates multiple shots using different stereotactic coordinates in order to improve conformity.
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Figure 3. Axial (top), sagittal (middle), and coronal (bottom) images showing the isodose lines of a lesion that was optimized efficiently using the shot-within-shot technique. Column A shows the original plan prescribed at the 50% IDL, and column B
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shows the optimized plan prescribed at the 62% isodose line. The difference in beam-on time was 22% with all other metrics being relatively equal except for the maximum dose within the target.
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Figure 4. Histogram highlighting the percent difference in gradient index when changing from a reference
intermediate dose in certain cases. Figure 1 shows the correlation between Dselectivity and DV12Gy for all cases in which a new plan was created (D ¼ Original e SWS50%). The correlation coefficient for this comparison was 0.75 (P ¼ 0.0012 using 2-tailed T-test). The correlation coefficient between volume and DV12Gy was 0.36 (P ¼ 7 1013) and between DGI and DV12Gy was 0.04 (P ¼ 6 106). The number of remaining lesions with DV12Gy <1 cc was 93. In addition, 86 lesions were found to have a DV12Gy <0.5 cc. Counting all exclusions, the percentage of lesions that could be effectively treated with the SWS technique (utilization rate) was calculated at 39%. Figure 2 shows axial, sagittal, and coronal isodose lines of the original and optimized plans for an excluded case (oblong lesion). Figure 3 shows the same information for an eligible case. In comparing the dose fall-off between the optimized and reference plans, Figure 4 highlights the percent difference in GI between the 2 datasets. On the basis of this histogram, it can be seen that in only one instance did the GI worsen by >5%. In addition, a total of 67 plans (72%) had a GI no worse than 3%. These numbers are relevant considering the optimization method was designed to ensure a similar dose fall-off to a plan prescribed at the 50% IDL using the SWS technique. The efficacy of SWS optimization is highlighted in Figure 5A and B. The top figure includes data on all 93 lesions for which new plans were created. The bottom figure excludes 17 lesions, which were originally prescribed at IDLs >50%. In a few of
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shot-within-shot (SWS) plan to an optimized SWS plan. All 93 eligible lesions were included in the comparison.
these cases, the beam-on time increased when applying the SWS technique. This resulted in the crossing of the solid and dotted lines seen in Figure 5A, where the lines themselves represent the difference in beam-on time when comparing the optimized plans with both the original and reference SWS plans. In the bottom figure, the optimized plan is always being compared with a plan prescribed at the 50% IDL, either the original or reference SWS plan. As a result, beam-on time never increases when plans are optimized. The area between the solid and dotted lines of Figure 5A and B indicates that beam-on time is reduced in many cases simply by applying the SWS technique. Additional reductions are then achieved by adding IDL optimization. In looking specifically at the histograms, which assess the time reduction between the 2 new plans (dotted lines), the extent of the curves matches expectations based on prior work. Here, the assumption was a maximum time reduction of roughly 40%, which was indeed seen in the current data. Simulations also previously demonstrated that IDL optimization would be most effective for targets that fell within 2 distance size ranges. Figure 6A plots DT (D ¼ SWS50% e SWSopt) as a function of effective target diameter calculated on the basis of an equivalent spherical volume. Figure 6B plots similar information as predicted on the basis of phantom studies. In comparing the 2 figures, the centers of the twin peaks are shifted, possibly due to the assumption of spherical shape in calculating an effective
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Figure 5. Cumulative histograms showing the reduction in beam-on time as a percentage of the total number of lesions included in the analysis. The top figure (A) includes all 93 eligible lesions. The bottom figure (B) excludes 17 lesions from the analysis for which the
diameter (i.e., true diameter effective diameter). The overall shapes and magnitudes, however, are consistent. The approximate size ranges associated with the 2 peaks in Figure 6A are 0.05e0.3 cc and 1.1e2.1 cc, respectively, when calculated using an equivalent spherical volume.
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original plan was prescribed at an isodose line >50%. The solid line represents the time difference between the optimized SWS plan and the original plan. The dotted line represents the time difference between the optimized SWS plan and the reference SWS plan.
DISCUSSION The results of this study indicate that almost 40% of otherwise unselected brain metastasis at our institution would be eligible for GK planning using the SWS technique with resultant reductions in treatment time. In practice, it is fairly easy to determine eligibility
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Figure 6. Histograms showing the reduction in beam-on time as a function of lesion diameter. The time difference is calculated between the optimized SWS plan and the reference SWS plan. The top figure (A) represents data as measured in the current study,
on the basis of lesion size, shape, and proximity to critical structures. Once a target has been deemed eligible, a reference plan can be created using the SWS technique prescribed at the 50% IDL. According to this study, the reference plan will in the majority of cases reduce beam-on time in comparison with other planning techniques that incorporate mixed collimation and/or multiple stereotactic coordinates. Once a reference plan is created, optimization of the prescription IDL and shot weighting should further reduce beam-on time for most cases. The amount of time reduction can be estimated (Figure 6). The trade-offs associated with these methods can be thought of in terms of intermediate dose, high dose, and maximum dose. In regards to intermediate dose, the current results show differences in V12Gy to be minimal (<0.5 cc in most cases), partly due to the maintenance of a steep dose gradient and partly due to the fact
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which includes 93 lesions. The bottom figure (B) represents the predicted relationship between DT and lesion diameter on the basis of phantom studies. The shape and magnitude of the distributions are similar, though there is a clear shift in the x-axis.
that eligible lesions are inherently small (Volmean ¼ 0.4 cc, Volmax ¼ 2.2 cc). A number of studies have stratified the risk of radiation necrosis based on V12Gy at increments of 5 cc (V12Gy > 0e 5 cc, 5e10 cc, etc.).2,3 It is left to the practitioner to decide for a given patient whether any marginal increase in V12Gy is relevant on the basis of such studies. In regards to high dose, most lesions showed only small differences in the conformity of the prescription dose to the target volume (Dselectivity <0.1 for 73/93 lesions). There were a few instances, however, in which this proved not to be the case (Dselectivity >0.2 for 5 lesions, max ¼ 0.3). Whether this is consequential likely depends on the location of the target to critical structures and eloquent regions of the brain parenchyma. In clinical practice, exclusions should be made on a case-by-case basis. Although multiple studies have shown no correlation between decreasing conformity and
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Figure 7. Histograms showing the number of cases for which a specific IDL was prescribed. The top figure represents the original choice of prescription IDL, and the bottom figure represents the prescription IDL after
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SWS optimization. The dotted line represents the inverse relationship between prescription IDL and maximum dose.
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increasing symptomatic radiation necrosis,5-8 this study did observe a correlation between changes in conformity and V12Gy. As the prescription IDL becomes less conformal, there is the potential for intermediate and low IDLs to gradually expand (see Figures 1 and 2). This may lead to an increase in V12Gy without a significant change in the GI. Thus even though the SWS technique is efficient at maintaining a steep dose gradient, conformity and its effect on intermediate dose may become a limiting factor if applying the method toward an ellipsoidal or irregularly shaped target. For lesions where this may be an issue, it is prudent to try other techniques in addition to the SWS method and then compare plans using DVH metrics. The correlation between conformity and V12Gy is an interesting (albeit intuitive) finding that applies broadly to GK planning. Finally, as with all GK plans, the prescription IDL is inversely correlated with maximum dose. Figure 7 highlights this relationship along with illustrating how the distribution of prescription IDLs in this study changed once optimization was included. While such a modification may seem drastic, it is important to keep in mind that both standard linear accelerator (LINAC) and robotic radiosurgery are commonly prescribed in the 65%90% IDL range without clear evidence of worse outcomes.9-11 Indeed, a number of recent studies have found no correlation between prescription IDL and local control/radiation necrosis7,12 or, more interestingly, that higher-prescription IDLs are positively correlated with local control.8,13 The working hypothesis for the latter result has to do with the broad penumbra traditionally associated with higher-prescription IDLs. For cases in which no prior margin exists, a broad penumbra mitigates the
1. Johnson P, Monterroso M, Yang F, Mellon E. Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique. Radiat Oncol. 2017;12, 187, 1-9. 2. Nuclear Regulatory Commission. Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units, 10 CFR 35.615. 2015. 3. Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy Gamma Knife radiosurgical volume is a predictor for radiation necrosis in non-avm intracranial tumors. Int J Radiat Oncol Biol Phys. 2006;64:419-424. 4. Lawrence Y, Li X, el Naqa I, et al. Radiation dosevolume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76:S20-S27. Kondziolka D, Pollock BE, et al. from arteriovenous malformation multivariate analysis and risk J Radiat Oncol Biol Phys. 1997;38:
6. Nakamura JL, Verhey LJ, Smith V, et al. Dose conformity of Gamma Knife radiosurgery and risk
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CONCLUSIONS In this work, both the utilization rate and efficacy of SWS optimization were assessed by replanning a cohort of 75 patients. The results showed that 39% of brain metastases were eligible for replanning. Excluded lesions included those larger than the 16-mm collimator, smaller than the 4-mm collimator, ellipsoidal or irregular in shape, or near critical structures. For the remaining subset, beam-on time was reduced through implementation of the SWS technique and then extended further through optimization of the prescription IDL and shot weighting. Time reductions on the order of 25%e30% were seen in approximately 40%e50% of eligible lesions. Only small differences were noted in the gradient index, conformity, and V12Gy for most cases in comparison with the original treatment plan.
factors for complications. Int J Radiat Biol Phys. 2003;81:115-119.
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5. Flickinger JC, Complications radiosurgery: modeling. Int 489-490.
effects of procedural uncertainty and potentially treats microscopic disease, which may extend beyond the visible tumor boundary. Although the penumbra was purposely kept sharp in the current study, the control afforded through optimization enables the creation of a variety of beam profiles and penumbra. Future work will further explore this option while investigating how such plans compare with those initially created with a margin, being mindful always of the effect on intermediate dose and potential for radiation necrosis. The expectation when using SWS optimization in the current form, however, is that neither local control nor radiation necrosis will be any worse than plans prescribed at the 50% IDL based on similar target coverage and levels of V12Gy.
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7. Shiue K, Barnett G, Suh J, et al. Using higher isodose lines for Gamma Knife treatment of 1 to 3 brain metastases is safe and effective. Neurosurgery. 2014;74:360-366. 8. Romano K, Trifiletti D, Garda A, et al. Choosing a prescription isodose in stereotactic radiosurgery for brain metastases: implications for local control. World Neurosurg. 2017;98:761-767. 9. Meeks S, Buatti J, Bova F, et al. Treatment planning optimization for linear accelerator radiosurgery. Int J Radiat Oncol Biol Phys. 1998;41: 183-197.
12. Jani A, Rozenblat T, Nanda T, et al. The energy index does not affect local control of brain metastases treated by Gamma Knife stereotactic radiosurgery. Neurosurgery. 2015;77:119-125. 13. Sharma M, Jia X, Ahluwalia M, et al. First followup radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastasis. Cancer Med. 2017;6:2076-2086.
Conflict of interest statement: The authors did not receive specific funding for this study. All data collection and analysis was performed as part of the routine clinical practice at the academic facility. The authors have no competing interest to disclose.
10. Sio T, Jang S, Lee SW, et al. Comparing Gamma Knife and Cyberknife in patients with brain metastases. J App Clin Med Phys. 2014;15:14-26.
Received 12 September 2018; accepted 16 November 2018
11. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363: 1665-1672.
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Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.140
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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