The main goal of modern radiotherapy is to optimize the delivery of radiation dose such that the target is fully sterilized while maximally sparing the surrounding healthy tissue and organs. Especially in head and neck (HN) cancers, this goal is challenging to achieve because organs at risk (OAR) are generally proximal to target volumes. Huguenin et al. had a quality of life study for HN patients received radiotherapy and revealed the highest morbidity was probably the result of using large radiation fields [1]. Therefore, reduction in irradiated volume and dose to local organs may lower the risk and severity of radiation induced complications [2]. Advanced conventional delivery techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have improved the outlook for OAR for HN patients in the past several decades [3]. Proton therapy has the potential to further improve OAR sparing and reduce integral dose resulting from the intrinsic physics of the proton beam [4].

Proton pencil beam scanning (PBS) technique is the current state of art of modern proton therapy. Generally, PBS dose can be shaped using either single-field uniform dose (SFUD) or intensity modulated proton therapy (IMPT) planning techniques. In SFUD, often called single-field optimization, fields are optimized simultaneously so that each field uniformly covers the whole target. In IMPT, fields are also optimized simultaneously, but each field does not uniformly cover the whole target and only the sum of all fields provides adequate and homogeneous target coverage, similar to IMRT. Although the flexibility of IMPT allows for creation of more complex dose distributions than SFUD, which improves OAR sparing in practice, concerns such as high sensitivity to uncertainties and lack of robustness for IMPT still exist [5]. In contrast, SFUD plans are considered to be more robust than IMPT due to less dose modulation and lower complexity of dose distributions for each individual field [6].

Uncertainties in proton therapy are expected from several sources. Setup errors (SE), considered only as shifts in conventional therapy, also cause dose distortions in proton therapy resulting from the displacement of heterogeneity in the beam path, to which protons are more sensitive than photons. Additionally, range uncertainties (RU) arise from conversion of computed tomography (CT) Hounsfield units (HU) to proton stopping power, CT artifacts, fluctuation of proton energy, anatomy change and so on. Typically, RU from ±3% to ±3.5% of HU is taken into consideration for routine clinical practice [7]. Uncertainties related to motion should be considered as well when evaluating proton therapy plans, especially for PBS treatments due to interplay effect [8]. As all of these uncertainties may result in significant deviations between planned and delivered dose distributions [9], it is very important to evaluate the robustness of proton therapy plans, especially for newly developed clinical protocols.

Several previous studies have investigated the robustness of proton therapy for HN cancer compared to photon techniques. Barten et al. studied OAR sparing and plan robustness for PBS proton planning techniques including SFUD and IMPT with more fields and compared these with VMAT photon plans. They reached conclusion that IMPT plans has improved OAR sparing but were less robust than SFUD and VMAT and robustness of the MFO plans did not increase with more fields [6]. Van der Voort et al. derived a “robustness recipe” for minimax robust optimization of IMPT treatment plans to ensure adequate CTV coverage for HN cancer patient relative to systematic setup, random setup and range errors [10]. Malyapa et al. evaluated the robustness of IMPT plans to setup and range uncertainties for HN patient and created a robustness database, which allows the identification of future plans that may benefit from alternative planning approaches to improve robustness [7]. Van de Water et al. quantified the impact of the degree of robustness against setup and range errors on OAR dose and normal tissue complication probabilities in IMPT proton therapy for HN cancer patient and concluded that minimizing setup errors should be given a higher priority than minimizing range errors [11].

In this work, a novel HN proton treatment planning geometry containing three SFUD fields (two posterior (oblique) fields and one anterior field, inversed “Y” shape) using superior-inferior gradient dose matching is presented. The dosimetrical advantages and plan robustness of this approach are first time evaluated relative to two-Arc VMAT plans, in terms of target and OAR dose levels.

This study presented a novel field geometry for HN patients receiving proton PBS treatment. The results of treatment planning comparisons between proton SFUD PBS delivery technique and VMAT photon radiotherapy for HN were reported, focusing on target coverage, OAR sparing and plan robustness for plans generated using commercial TPS (without robust optimization). The planning method containing two PBS posterior-oblique fields (POF) was first developed and used to treat HN patients at our institution. Considering the shape of typical HN target volumes, the selection of POF was used to improve the sparing of normal organs anterior to the target volumes, and reduce their treatment related toxicities. In contrast to VMAT plans, this goal could be achieved for most of the proton HN patients when there was no direct overlap between organs and target volumes. However, verification plans based on repeated CT scanning showed potentially large coverage variations to nodal volumes

Note: ∆: Standard Deviations.

located in the lower neck [17]. These nodal targets were typically shallow, from an anterior beam direction. Therefore, POF had to travel a longer beam path to reach them. Loose tissues on the back of the neck can fold differently from day to day and it was a challenge to achieve the goal of reproducibility for this loose tissue, especially for larger/older patients. Neither surface guidance with optical images, nor kV images during patient setup, are capable of flagging this change of tissue shape on the back of the patient’s neck, which could significantly impact the POF proton beam path, and translate into range errors and reduced target coverage. However, it also showed consistency and robustness of the POF to target coverage and OAR sparing for volumes superior to the thyroid notch. Therefore, a revised planning method was proposed to separate the target volume into two sets, depending on their locations relative to the thyroid notch, and to add an anterior field to cover the lower target set [18]. Gradient dose matching was applied to create a “soft dose buffer” between two abutting field sets to reduce planning complications and dose uncertainties associated with the junction. The revised method has become our standard approach for proton treatment of HN patients.

One novelty of this work originates from the employment of gradient dose matching for the anterior and posterior field target sets in HN planning with a PBS technique. Different from the field matching in craniospinal irradiation, all fields here share the same isocenter in HN proton therapy and no couch shift is required between fields during treatment. Along with the fact that patient’s head and neck area is immobilized by a thermoplastic mask, that effectively limits the patient’s intrafractional movement along craniocaudal direction, so variations in daily setup should result in a wash-out effect along the junction [19], and large systematic setup errors are restricted for HN treatment through the use of accurate online imaging systems. According to the mathematic model for gradient field match developed by Lin [12], given a systematic setup error of 2 mm, maximal ~5% dose errors are expected at junction of 4 cm using gradient dose match. Thus, a junction length of 4 cm (shown in Figure 2) is considered to be reasonable to maintain a safe dose to critical organs, such as cord, and uniform coverage to target volumes in the junction area by adding the wash-out effect due to daily setup variations.

Another novelty comes from the selection of proton beam angles. Posterior fields provide sparing on the OARs anterior to treatment volumes, including optical system, as well as organs and tissues in oral cavity. However, the dose deviation caused by range uncertainties, which could be the dominant uncertainty factor as illustrated in this study, has to be assessed during plan evaluation. Large dose variations are generally expected for distally located small organs, such as the submandibular gland, especially when overlap with target volumes is present. In contrast to VMAT, higher mean dose is often observed for the submandibular glands overlapping with target volumes in a proton plan because extra margin is typically added distally to accommodate range uncertainties, so more normal tissue volume distal to the PTV receives the prescribed dose. However, Proton could provide significant sparing when no direct overlap occurs, such as for patient 6. Moreover, critical organs such as brainstem and spinal cord are placed laterally to the field to avoid unpredicted dose uncertainties caused by range uncertainty and enhanced radiobiological effect at the distal end of the Bragg peak [20]. It is easy to understand why setup uncertainties dominate the dose variations for these laterally positioned organs, as indicated in this study. Maximal cord dose between 45 Gy and 50 Gy was found for two patients (1 and 3) in a specific combination of SE and RU in their robustness study. Concerns on safe cord dose are reduced not only because minimal (<0.5cc) volume received dose of 45 Gy and above, these values represent the cord doses in the worst case scenario (consider SE as systematic errors through treatment course) and daily setup variation is ignored. Moreover, bony landmarks proximal to these organs, such as cervical vertebrae, are generally considered for patient setup to confirm the accuracy of patient alignments.

The robustness evaluation in this study is limited to SE and RU. The effect of patient’s inter- and intra-fractional shifts, which could potentially smear the dose deviations predicated by the uncertainty study [21], were not investigated. With modern imaging guided therapy, the risk of 2.25 mm SE in all three directions simultaneously is low, especially for HN cases with immobilization devices and special attention given to precise patient positioning. Further research is needed to investigate the dose uncertainties due to anatomic changes using online volumetric imaging [22] or repeating CT scans [23], as well as variation in relative biological effectiveness [24]. It would also be desirable to explore robust optimization algorithms during plan optimization to simultaneously strive for a robust plan with optimal OAR sparing [25] [26]. Furthermore, with the development of fast and accurate dose calculation algorithms [27] and advanced online imaging analysis tools [28], application of adaptive proton therapy on HN treatment should also be considered.

This study presented proton PBS treatments with a novel proton beam geometry of three SFUD fields for HN patients. The robustness of the proton plans was assessed based on RU and SE, and was compared to VMAT results. It demonstrated that a proton plan with three SFUD fields can lead to robustness similar to that of VMAT, even without robust optimization algorithms, while providing significant sparing to larynx, contralateral parotid and oral cavity.

We would like to thank the radiation oncology group in Roberts Proton Therapy Center at the University of Pennsylvania for their continuous supports on this project. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Huang, S., Liu, H.Y., Shen, J.J., Zhai, H.F., Kirk, M., Hartl, B., Lin, A., McDonough, J., Both, S. and Lin, H.B. (2018) Robustness Evaluation of a Novel Proton Beam Geometry for Head and Neck Patients Treated with Pencil Beam Scanning Therapy. International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 7, 308-322. https://doi.org/10.4236/ijmpcero.2018.73025