Improving Head and Neck Cancer Treatments Using Dynamic Collimation in Spot Scanning Proton Therapy

Abstract

Purpose:

Interest in using collimation for spot scanning proton therapy has recently increased in an attempt to improve the lateral penumbra. To investigate the advantages of such an approach for complex targets, a plan comparison between uncollimated and collimated beam spots was performed for patients with head and neck cancer.

Patients and Methods:

For 10 patients with head and neck cancer, previously treated with spot scanning proton therapy, uncollimated and collimated treatment plans were created using an in-house treatment-planning system capable of modeling asymmetric-beamlet dose distributions resulting from the use of a dynamic collimation system. Both uncollimated and collimated plans reproduced clinically delivered plans in terms of target coverage. A relative plan comparison was performed using both physical and radiobiological metrics on the organs at risk.

Results:

The dynamic collimation system improved dose-distribution conformity while preserving target coverage. The median reduction of the mean dose to the esophagus, uninvolved larynx, and uninvolved parotids were −11.9% (minimum to maximum, −6.4% to −24.1%), −7.2% (−0.8% to −60.1%), and −5.2% (−0.2% to −21.5%), respectively, and depended on the organ location relative to the target and radiation beam angle. The collimation did not improve dose to some organs at risk surrounded by the target or located upstream of Bragg peaks because of the priority on the target coverage.

Conclusion:

In spot scanning proton therapy, the dynamic collimation system generally affords better target conformity, which results in improvement in organ-at-risk sparing in the head and neck region while preserving target coverage. However, the benefits of collimation and the increased complexity should be considered for each patient. Patients with large bilateral targets or organs at risk surrounded by the target showed the least benefit.

Introduction

Low-energy spot scanning proton therapy (SSPT) treatments suffer from poor conformity because of increased lateral spot size [1–3], which is further increased with patient scattering. Wang et al [1], van de Water et al [2], and Widesott et al [3] have found that, to improve plan quality over the state-of-the-art photon techniques for brain or head and neck cancers, the in-air spot size, defined as the sigma (σ_air) of the Gaussian function used to represent fluence in the beam's eye view of a proton pencil beam, must have a value of approximately 4 mm. Unfortunately, spots of this size at low energies do not seem achievable with current clinical equipment [4–6], even with the IBA-dedicated nozzle (IBA International, Louvain-La-Neuve, Belgium) which is known to have one of the smaller spot sizes commercially available [7]. However, collimation devices for SSPT, such as apertures or multileaf collimators, can potentially reduce the effective σ of a proton pencil beam and improve overall plan quality [8, 9]. Hyer et al [10, 11] recently proposed a theoretical novel dynamic collimation system (DCS) with a small footprint that can provide collimation to SSPT at each beam spot.

An earlier study [12] investigating the clinical benefits of the DCS for brain treatments found that the DCS was able to greatly improve target conformity and normal tissue sparing, while maintaining target coverage, with an average mean dose reduction to normal brain tissue of 25.1%. Although head and neck cancers often have much larger target volumes and more-complex shapes than do the brain tumors studied previously, we believe that these patients may also benefit from the use of the DCS, largely because target volumes are often located near many organs at risk (OARs). With the ability to reduce the effective spot size and further improve dose conformity, using the DCS in SSPT is expected to increase or maintain tumor control probability while decreasing acute and late toxicities [13]. The purpose of this study was to evaluate the use of the DCS for head and neck tumors and retrospectively quantify the benefits of the DCS in 10 patients previously treated with SSPT.

Materials and Methods

Patient Selection and Planning Method

Treatment planning images and data for 10 patients with head and neck cancer (Table 1) treated previously at the University of Pennsylvania Proton Therapy Center (Philadelphia) were obtained through an institutional review board–approved research protocol and data sharing agreement. The patients were originally planned using a commercial proton treatment planning system (Eclipse version 11, Varian Medical Systems, Palo Alto, California) and treated on an IBA ProteusPlus system equipped with a Universal Nozzle. The plan characteristics are summarized in Table 1. The beam characteristics of the Universal Nozzle are described by Lin et al [14]. The clinical plans used SSPT with a single-field optimization approach, except for 2 plans (P2 and P3) that utilized a boost planned with multifield optimization. The single-field optimization considers each beam individually, whereas the multifield optimization takes into account all beams simultaneously. The plans were optimized to pencil beam-scanning planning target volumes (PBSTV), which are defined as a 5-mm uniform expansion from the clinical target volume to account for setup and range uncertainties. Some plans had multiple PBSTVs with different dose prescriptions that were joined in a structure named the PBSTV composite for ease of display and analysis of the dose-volume histogram (DVH) curves. The PBSTV composite volumes for patients P1 to P10 were 500, 1004, 591, 822, 290, 436, 305, 200, 272, and 332 cm³, respectively. Other plan characteristics, such as individual PBSTV volumes, dose prescriptions, and beam incidences, are described in Table 1. The initial clinical plans were designed such that 95% of each PBSTV received the prescribed dose. The OAR dose constraints used for planning purposes were mean dose (D_mean) <  20 Gy for the esophagus, larynx, oral cavity, and contralateral parotid; D_mean < 26 Gy for the ipsilateral parotid, D_mean < 39 Gy for the contralateral submandibular gland; maximum dose (D_max) < 54 Gy for the brain stem, D_max < 45 Gy for the cord, and D_max < 50 Gy for the 5-mm expansion of the cord.

Table 1.

Plan characteristics.

Patient No.	Target location	PBSTV dose prescription (Gy)	PBSTV volume (cm3)	Bean incidence
P1	Bilateral: SCC of the tongue base	54 60	235 254	Left posterior Right posterior
P2	Bilateral: SCC of the left oral tongue	59.5 63 70 72.1	284 261  23 365	Left posterior Right posterior Left posterior oblique
P3	Bilateral: SCC of the left oral tongue, recurred in bilateral neck	54 57 60 63 66	73 231 145  22  45	Left posterior Right posterior Right posterior oblique Anterior
P4	Bilateral: SCC of the right tonsil	54 60	408 452	Left posterior Right posterior
P5	Unilateral: SCC of the right pyriform sinus	54 60	241  43	Right posterior Posterior
P6	Unilateral: SCC of the left supraglottic larynx	50.4	436	Left anterior oblique Left posterior oblique
P7	Unilateral: carcinoma of the left parotid gland	60 63	256  36	Left anterior oblique Left posterior oblique
P8	Central: recurrent head and neck cancer involving the oropharynx	70	188	Left posterior oblique Right posterior oblique
P9	Unilateral: recurrent basal cell cancer of the scalp, metastatic to the left neck lymph node	54 60 63	71  95  36	Left anterior oblique Left posterior oblique
P10	Unilateral: recurrent SCC of the skin, with spread to the left parotid	70.4	332	Left lateral Left posterior oblique

Abbreviations: PBSTV, pencil beam scanning planning target volumes; SCC, squamous cell carcinoma.

The clinically delivered SSPT plans were used as a reference to which uncollimated plans generated by our in-house treatment-planning system RDX were matched, mainly in terms of target coverage. RDX has been previously used for other studies involving proton-dose calculation [15, 16] and is capable of modeling asymmetric beamlets resulting from collimation [17]. The ability of RDX to calculate both collimated and uncollimated treatment plans eliminates any variance from different planning systems and allows the benefits of the DCS to be directly quantified. The beam angles of uncollimated and collimated plans in RDX were chosen so that the beam entered parallel to the long axis of the target structure, as shown in Figure 1. These beams are consistent with recommendations of Frank et al [18], who suggested an angle selection based on the premise of placing the Bragg peaks lateral to the spinal cord and minimizing the uncertainties produced by density heterogeneities along the beam path by avoiding beams going through the mouth and teeth. The initial PBSTV outlines of bilateral targets were split into left and right sides using the middle line to benefit from the spot collimation for OARs in the middle of the neck surrounded by the bulky target. A left posterior beam was used to calculate the left target beamlets, whereas a right posterior beam was used for the right target. Then, both beamlet batches were merged for the optimization calculation of beamlet weights.

Figure 1.

Two typical beam setups for 2 target geometries, 1 a bulky tumor surrounding the cord (grey circle): field geometries (blue) with target outlines (orange). Abbreviations: LPO, left posterior oblique; LAO, left anterior oblique; LPOST, left posterior; RPOST, right posterior.

A model of the IBA Universal Nozzle was used for the uncollimated plans in RDX. For the collimated plan, the effects of the DCS were added to the IBA Universal Nozzle. The modeling of the collimated beamlets for the clinical range of proton energy was validated and implemented in RDX by Gelover et al [17]. The spot spacing used for the plans was 3 mm, and energy layer separation was 5 mm. Both the spot spacing and energy layer separation were different from those used for the initial clinical plans. The rationale for using a reduced x to y spot spacing is that a smaller σ size must be compensated for by reducing the distance between spots to obtain adequate coverage without hot spots [3]. The energy layer separation was set to be constant in RDX, whereas it was varying with energy based on the incident energy spread of the beam in Eclipse. Once the uncollimated plans were generated, collimated plans were created in RDX using the same gantry angles, beam spots, and energy layers for comparison purposes, but future collimated plans outside the scope of this study might be planned using optimized beam angles. Although the DCS is theoretically able to collimate each beam spot, only spots around the target boundary were collimated in practice because the beam spots inside the target do not need collimation. As shown by Wang et al [19], the use of a collimation requires considering a target expansion for spot placement to ensure the target coverage: in this study, a 6-mm margin was chosen because that is the maximum displacement of the beamlet centroid by the DCS obtained through simulation by Gelover et al [17].

Evaluation Tools

The cumulative DVH curves of the target and OARs were used for initial evaluation. A focus on either the D_mean or the D_max dose (D_1%) was made depending on the OAR, with D_1% corresponding to 1% of the organ volume on the cumulative DVH. The PBSTV coverage was assessed using D_95% of each individual PBSTV volume. The homogeneity index (HI) and conformity index (CI 50%) were calculated for further evaluation of the treatment plans. The HI is defined as the difference between the dose received by at least 95% of the PBSTV volume and the dose received by at least 5% of the PBSTV, normalized to the PBSTV D_mean: (D_95% − D_5%)/D_mean. The CI 50% is the ratio between the patient volume receiving at least 50% of the prescribed dose and the PBSTV volume. The PBSTV coverage and HI were chosen to quantify the PBSTV dose distribution similarity between the uncollimated and collimated plans, whereas the CI 50% was chosen to quantify any improvement in dose distribution conformity. For OARs, D_mean or D_1% are reported. In the analysis, an uninvolved structure means the part of the structure that was outside any planning target volume.

Normal tissue complication probability (NTCP) was calculated for the parotid glands, esophagus, oral cavity, and cord using the Lyman-Kutcher-Burman model [20]; the parameters for the computation were summarized by Luxton et al [20] and Jakobi et al [21].

The RayStation treatment planning system (version 3.99, RaySearch Laboratories, Stockholm, Sweden) was used to render dose distributions and compute the DVH for the both uncollimated and collimated plans.

Statistical significance was evaluated with a Student t test to provide a 95% confidence interval (95% CI) and a P value.

Results

Target Coverage

The equivalence of target coverage in the uncollimated and collimated plans was verified through the comparison of the PBSTV DVH, the 95% PBSTV coverage, and the HI. Although most patients have more than one target volume, for simplicity, only the comparison of the PBSTV composite DVH is shown in Figures 2 and 3. The PBSTV DVHs were nearly identical. Only small discrepancies were observed (maximum difference of 1.4%) for the PBSTV coverage and a close HI (maximum difference of 0.02) as reported in Tables 2 and 3 for all patients.

Figure 2.

Dose-volume histograms of the pencil beam-scanning planning target volumes composite and relevant organs at risk for patients P1 to P6; the uncollimated plan is in solid lines and the collimated plan is in dashed line. * indicates that only the uninvolved portion of the organ at risk was considered.

Table 2.

Homogeneity index (HI) and conformity index based on 50% of the prescribed dose (CI 50%) for each target (pencil beam scanning planning target volumes [PBSTV]) of all patients and their relative difference to the uncollimated plan.

Patient No.	Treatment	PBSTV 1		PBSTV 2		PBSTV 3		PBSTV 4		PBSTV 5
		HI	CI 50%	HI	CI 50%	HI	CI 50%	HI	CI 50%	HI	CI 50%
P1	Uncol	0.12	3.87	0.06	7.15	—	—	—	—	—	—
	Col	0.11	3.59	0.07	6.64	—	—	—	—	—	—
P2	Uncol	0.19	2.75	0.18	3.88	0.09	6.34	0.07	6.65	—	—
	Col	0.20	2.69	0.19	3.82	0.09	6.28	0.08	6.62	—	—
P3	Uncol	0.04	2.94	0.09	3.34	0.09	6.79	0.07	21.33	0.06	31.26
	Col	0.06	2.71	0.10	3.09	0.09	6.31	0.08	19.92	0.06	29.37
P4	Uncol	0.13	3.93	0.09	7.22	—	—	—	—	—	—
	Col	0.13	3.41	0.11	6.31	—	—	—	—	—	—
P5	Uncol	0.09	4.58	0.06	28.00	—	—	—	—	—	—
	Col	0.09	4.38	0.06	26.76	—	—	—	—	—	—
P6	Uncol	0.06	2.22	—	—	—	—	—	—	—	—
	Col	0.08	2.01	—	—	—	—	—	—	—	—
P7	Uncol	0.05	1.93	0.05	15.36	—	—	—	—	—	—
	Col	0.06	1.68	0.05	13.49	—	—	—	—	—	—
P8	Uncol	0.11	2.65	—	—	—	—	—	—	—	—
	Col	0.11	2.34	—	—	—	—	—	—	—	—
P9	Uncol	0.06	2.79	0.11	3.99	0.04	14.68	—	—	—	—
	Col	0.07	2.48	0.10	3.48	0.04	12.74	—	—	—	—
P10	Uncol	0.16	1.92	—	—	—	—	—	—	—	—
	Col	0.17	1.72	—	—	—	—	—	—	—	—

Abbreviations: Uncol, uncollimated; Col, collimated.

Dose-Conformity Improvement and Organ-at-Risk Dose Reduction

Dose distributions from the uncollimated and collimated plans and the difference for one patient (P5) are shown in Figure 4. The improvement in target conformity can be directly observed in the dose difference in Figure 4c. The values of CI 50% are reported in Tables 2 and 3 to demonstrate the improvement in conformity afforded by the DCS as well as the variability depending on the target volume and shape. The conformity improvement by the DCS was also observed through the significant reduction of the mean dose to the 10-mm ring surrounding the PBSTV, yielding an average decrease of 7.1% (95% CI, 4.4% to 9.8%; P value < .001).

Figure 4.

(a) Uncollimated plan, (b) collimated plan, and (c) relative difference (%) between the 2 dose distributions for 1 patient (P5). The target is shown in black, the 10-mm normal tissue margin is shown in white, the right uninvolved parotid gland is shown in blue, and the uninvolved larynx is shown in green.

Figure 3.

Dose-volume histograms of the pencil beam-scanning planning target volumes composite and relevant organs at risk for patients P7 to P10; the uncollimated plan is in solid lines and the collimated plan is in dashed line. * indicates that only the uninvolved portion of the organ at risk was considered.

The collimated and uncollimated plans were also compared in the DVHs of selected OARs, as shown in Figures 2 and 3. The collimated plans showed reduced D_mean or D_1% to OARs adjacent to the target compared with the uncollimated plan. The values for selected OARs are reported in Tables 2 and 3. For each patient, a graphical summary of the OAR having a D_mean or D_1% difference > ± 2% (arbitrary value) between the uncollimated and collimated plan is shown in Figures 5 and 6.

Table 3.

The mean or maximum dose to some relevant organs at risk for both the uncollimated (Uncol) and collimated (Col) plans and their relative difference (Rel diff) to the uncollimated plan. The median, minimum, and maximum of the relative difference are also shown.

Patient No.	Treatment	Mean dose (cGy)										Max dose (cGy)
		Esophagus	Mandible*	Oral Cavity*	Larynx*	Parotid*		Submandibular gland*		Ear mid		Brain stem	Cord
						Lt	Rt	Lt	Rt	Lt	Rt
P1	Uncol	2173	1600	465	2479	3152	858	—	3468	2917	—	3661	2435
	Col	1986	1262	311	2449	2835	839	—	2238	2964	—	3202	1566
	Rel diff (%)	−8.6	−21.1	−33.1	−1.2	−1.8	−2.2	—	−35.5	1.6	—	−12.5	−35.7
P2	Uncol	2329	3200	2985	3065	—	2018	—	—	2950	2467	4713	4036
	Col	2075	3050	2827	2889	—	1980	—	—	2993	2296	4254	3854
	Rel diff (%)	−10.9	−4.7	−5.3	−5.7	—	−1.9	—	—	1.5	−6.9	−9.7	−4.5
P3	Uncol	2525	3771	2102	2699	1395	1672	—	—	—	—	—	219
	Col	2363	3628	1814	2563	1388	1585	—	—	—	—	—	37
	Rel diff (%)	−6.4	−3.8	−13.7	−5.0	−0.5	−5.2	—	—	—	—	—	−83.1
P4	Uncol	1110	2587	1111	2165	1439	3331	5689	—	—	4462	4691	3404
	Col	845	2198	873	1979	1130	2978	4149	—	—	3646	4509	2870
	Rel diff (%)	−23.9	−15.0	−21.4	−8.8	−21.5	−10.6	−27.1	—	—	−18.3	−3.9	−15.7
P5	Uncol	958	164	—	3960	—	2285	—	4086	—	3371	2486	3899
	Col	727	154	—	3896	—	2135	—	3505	—	2757	2443	3953
	Rel diff (%)	−24.1	−6.1	—	−1.6	—	−6.6	—	−14.2	—	−18.2	−1.7	1.4
P6	Uncol	1716	—	155	684	3504	—	—	—	205	—	—	1388
	Col	1494	—	75	478	3496	—	—	—	116	—	—	903
	Rel diff (%)	−12.9	—	−51.6	−30.1	−0.2	—	—	—	−43.4	—	—	−34.9%
P7	Uncol	—	872	282	972	—	—	3654	—	4524	—	—	616
	Col	—	795	195	388	—	—	3293	—	3887	—	—	125
	Rel diff (%)	—	−8.8	−30.9	−60.1	—	—	−9.9	—	−14.1	—	—	−79.7%
P8	Uncol	—	2631	2335	509	2767	3510	—	—	120	—	313	994
	Col	—	2160	2325	505	2736	3256	—	—	73	—	269	844
	Rel diff (%)	—	−17.9	−0.4	−0.8	−1.1	−7.2	—	—	−39.2	—	−14.1%	−15.1%
P9	Uncol	—	846	—	864	—	—	3685	—	1393	—	1360	1882
	Col	—	681	—	645	—	—	3499	—	1160	—	1340	1795
	Rel diff (%)	—	−19.5	—	−25.3	—	—	−5.0	—	−16.7	—	−1.5%	−4.6%
P10	Uncol	—	551	260	717	—	—	3850	—	7112	—	1676	626
	Col	—	401	146	492	—	—	3173	—	7151	—	1208	148
	Rel diff (%)	—	−27.2	−43.8	−31.4	—	—	−17.6	—	0.5	—	−27.9%	−76.4%
	Median	−11.9	−15.0	−32.0	−7.2	−5.2		−15.9		−15.4		−9.7	−25.3
	Min	−6.4	−3.8	−0.4	−0.8	−0.2		−5.0		1.6		−1.5	1.4
	Max	−24.1	−27.2	−51.6	−60.1	−21.5		−35.5		−43.4		−27.9	−83.1

Note: An asterisk (*) Indicates that only the uninvolved part of the organ at risk was considered.

Abbreviations: cGy, centigray; Max, maximum; Lt, left; Rt, right; mid, middle; min, minimum.

Figure 5.

Absolute mean dose (D_mean) or maximum dose (D_1%) to some relevant organs at risk (OARs) for both the uncollimated (circle) and collimated (triangle) plans, and the difference normalized to the uncollimated plan (grey bar) for patients P1 to P4. P1 to P4 are patients with bilateral target, the other with unilateral targets.* indicates that only the uninvolved part of the OAR was considered. Abbreviations: Esoph, esophagus; Mandib, mandible; OC, oral cavity; Subm, submandibular gland; Par, parotid; BS, brain stem; ON, optic nerve; TL, temporal lobe; EarM, ear mid; TMJ, temporomandibular joint; Lt, left; Rt, right.

Figure 6.

Absolute mean dose (D_mean) or maximum dose (D_1%) to some relevant organs at risk (OARs) for both the uncollimated (circle) and collimated (triangle) plans, and the difference normalized to the uncollimated plan (grey bar) for patients P5 to P10. P1 to P4 are patients with bilateral target, the other with unilateral targets. * indicates that only the uninvolved part of the OAR was considered. Abbreviations: Esoph, esophagus; Mandib, mandible; OC, oral cavity; Subm, submandibular gland; Par, parotid; BS, brain stem; ON, optic nerve; TL, temporal lobe; EarM, ear mid; TMJ, temporomandibular joint; Lt, left; Rt, right.

Toxicity Reduction through Radiobiological Modeling

The NTCP values for the toxicities affected by the DCS are presented in Table 4. The largest improvements of the parotid gland NTCP for the risk of xerostomia were observed in patients P1, P5, and P8. The largest improvements of the esophagus NTCP for acute toxicity were observed in patients P1 and P2. A noticeable improvement of the larynx NTCP for the risk of edema was only observed in patient P7. The largest improvements of the larynx NTCP for aspiration pneumonia were observed in patient P2, P4, and P7. Some NTCP values were increased after collimation, but none by > 0.7%.

Table 4.

Absolute normal tissue complication probability (NTCP; %) for both the uncollimated (Uncol) and collimated (Col) plans, and their absolute difference NTCP_collimated − NTCP_uncollimated (relative difference to the uncollimated plan between parentheses) for relevant organs at risk.

Patient No.	Treatment	Parotid (%)		Esophagus (%)	Larynx (edema) (%)	Larynx (aspiration) (%)
		Left	Right
P1	Uncol	92.7	0.23	10.4	25.3	17.8
	Col	81.9	0.20	8.6	25.7	17.5
	Difference	−10.8 (−11.7)	−0.03 (−13.5)	−1.8 (−17.4)	0.4 (1.7)	−0.3 (−1.9)
P2	Uncol	100	31.6	9.5	87.8	39.3
	Col	100	28.5	7.5	88.1	37.1
	Difference	0.0 (0.0)	−3.1 (−9.8)	−2.0 (−20.9)	0.3 (0.3)	−2.3 (−5.7)
P3	Uncol	0.76	2.9	10.6	0.18	3.2
	Col	0.74	2.0	9.5	0.03	2.6
	Difference	−0.02 (−2.6)	−0.9 (−32.0)	−1.1 (−10.3)	−0.15 (−82.8)	−0.6 (−21.3)
P4	Uncol	0.52	96.0	2.8	9.8	14.4
	Col	0.08	87.6	1.9	12.7	12.7
	Difference	−0.44 (−84.3)	−8.4 (−8.7)	−0.9 (−30.7)	2.9 (29.2)	−1.7 (−12.1)
P5	Uncol	—	41.9	1.4	81.6	55.3
	Col	—	32.2	1.4	81.8	54.7
	Difference	—	−9.7 (−23.0)	0.0 (2.2)	0.2 (0.2)	−0.6 (−1.0)
P6	Uncol	99.3	—	4.6	1.9	4.5
	Col	99.3	—	3.6	1.5	3.7
	Difference	0.1 (0.1)	—	−0.9 (−20.5)	−0.4 (−18.6)	−0.8 (−17.2)
P7	Uncol	—	—	—	8.8	5.7
	Col	—	—	—	3.6	3.4
	Difference	—	—	—	−5.2 (−59.4)	−2.4 (−41.2)
P8	Uncol	44.3	90.5	0.3	74.2	12.7
	Col	42.0	79.2	0.3	74.9	12.7
	Difference	−2.3 (−5.2)	−11.3 (−12.5)	0.0 (−3.3)	0.7 (1.0)	0.1 (0.4)
P9	Uncol	100	—	0.27	4.4	5.2
	Col	100	—	0.27	3.7	4.3
	Difference	0.0 (0.0)	—	0.0 (0.0)	−0.8 (−16.9)	−0.9 (−17.8)
P10	Uncol	100	—	0.28	5.2	4.5
	Col	100	—	0.27	4.5	3.7
	Difference	0.0 (0.0)	—	−0.01 (−3.6)	−0.7 (−12.9)	−0.9 (−18.8)

Discussion

The collimated plans maintained the target coverage of the uncollimated plans. Noticeable improvement of the OAR sparing was observed for most of the 10 head and neck plans. For parotid sparing, 5 of 10 patients benefitted from the addition of collimation. All patients benefitted from the addition of collimation in sparing of the uninvolved submandibular gland, because the D_mean was systematically high (> 34.7 Gy) in uncollimated plans and greatly reduced by the collimation (from −5.0% to −35.5%). Four of 10 patients benefitted from the addition of collimation in sparing the uninvolved mandible, oral cavity, and the larynx and esophagus because the D_mean values close to, or slightly beyond, the usual clinical constraints were reduced. Only 1 patient had a relatively minor benefit from collimation. In that case (P6), the dose to most OARs with the uncollimated plan were already sufficiently low relative to the clinical constraints used for the treatment planning; therefore, the small dosimetric improvement was not considered sufficient to advise the use of the DCS. Regarding the radiobiological metrics, Nguyen et al [22] showed that it is more reliable to focus on the relative difference of the NTCP values instead of the absolute difference because of NTCP model uncertainties. Based on this argument, the results provide evidence that the DCS affords a significant reduction in different complication probabilities: for instance, 6 of 9 plans had great relative reductions in xerostomia risk (NTCP to the parotids), suggesting potential clinical significance.

Results from the 10 patients also indicate that the therapeutic benefit of the DCS for the treatment of head and neck cancer by SSPT is dependent on beam orientation as well as properties of the target, such as its shape, volume, and location relative to the OAR. For instance, P9 had a great conformity improvement for each PBSTV, whereas P2 demonstrated little improvement in conformity. The major difference between P2 and P9 was the extent of the target; P2 had a bilateral PBSTV with a volume close to the full neck compared with the unilateral PBSTV of P9 with a volume nearly 4 times smaller than that for P2. The variability in OAR sparing depending on these parameters was also described by Jakobi et al [21] when comparing intensity-modulated photon therapy to intensity-modulated proton therapy to identify a subgroup of patients who would most benefit from proton therapy. In the present study, unilateral targets generally benefitted the most from collimation by normal tissue sparing; however, fewer OARs are likely to be spared with unilateral targets than with bilateral targets because of the lesser extent of the disease. These bilateral targets are also challenging because of target coverage robustness from the splitting of the target structure to benefit from the dynamic collimation for the OARs in the middle of the neck.

The benefit of DCS remains theoretical because this was an in silico study. In addition, this study evaluated only a subset of head and neck plans, which may not be representative of all head and neck tumors encountered in clinical practice or in other tumor locations. Many variables influence target conformity, such as the energy layer, spot spacing, spot size, and the use of range shifter. However, those values were chosen to be representative of clinical plans and were identical between the uncollimated and collimated plans, except for the spot size and spot spacing, because the collimation changes the spot geometry (sharper penumbra and asymmetry) requiring a slight spot-spacing reduction. A previous study based on brain tumor plans [12] can be used as a point of comparison to detail the behavior of a DCS-based plan, depending on the plan and target properties. For the head and neck plans, improvement in D_mean to the 10-mm ring of normal tissue surrounding the target was slightly more than one-half of that obtained for the brain plans (−7.1% versus −13.7%). The main difference was that the brain tumors were smaller and more regularly shaped. The principal challenges with the head and neck plans included large target volumes with little ability to spare normal tissue, bulky tumors wrapped around the OAR with part of the beam crossing through the OAR to reach the target, and OARs partially intersecting the target or directly at the target boundary (Supplementary Data 1, 10.14338/IJPT-15-00036.1.S1 ^{(2.6MB, pdf)} ). A minor challenge was related to a slight increase in the entrance dose by the DCS [17]. Given these challenges, the DCS did not yield uniform improvement in sparing for every OAR for each plan. Although general conclusions can be drawn from this study, the use of the DCS must still be considered for each individual plan by weighing the clinical benefit against the additional complexity. The DCS can be considered an optional collimation system offering plan improvement dependent on the target complexity and at a low-cost for treatment delivery time (theoretically, between 29 s and 84 s, depending on the target size and the number of beams, assuming a continuous motion of the trimmer blades at a velocity of 0.35 m/s).

Future developments with an adaptive method for spot placement using contour scanning and eliminating spots too far away from the target boundary are expected to further decrease the dose to normal tissue and to partially solve the limited improvement for OARs surrounded by the target in patients with head and neck cancer.

Conclusion

In SSPT, the DCS generally affords better target conformity, which results in an improvement in OAR sparing in the head and neck region while preserving target coverage. However, the benefits of collimation and increased complexity should be considered for each patient. Patients with large bilateral targets or OARs surrounded by the target showed the least benefit.