Shikui Tang

Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation

BACKGROUND As proton beam radiation therapy (PBRT) may allow greater normal tissue sparing when compared with intensity-modulated radiation therapy (IMRT), we compared the dosimetry and treatment-related toxicities between patients treated to the ipsilateral head and neck with either PBRT or IMRT. METHODS Between 01/2011 and 03/2014, 41 consecutive patients underwent ipsilateral irradiation for major salivary gland cancer or cutaneous squamous cell carcinoma. The availability of PBRT, during this period, resulted in an immediate shift in practice from IMRT to PBRT, without any change in target delineation. Acute toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS Twenty-three (56.1%) patients were treated with IMRT and 18 (43.9%) with PBRT. The groups were balanced in terms of baseline, treatment, and target volume characteristics. IMRT plans had a greater median maximum brainstem (29.7 Gy vs. 0.62 Gy (RBE), ​P < 0.001), maximum spinal cord (36.3 Gy vs. 1.88 Gy (RBE), ​P < 0.001), mean oral cavity (20.6 Gy vs. 0.94 Gy (RBE), ​P < 0.001), mean contralateral parotid (1.4 Gy vs. 0.0 Gy (RBE), P<0.001), and mean contralateral submandibular (4.1 Gy vs. 0.0 Gy (RBE), ​P < 0.001) dose when compared to PBRT plans. PBRT had significantly lower rates of grade 2 or greater acute dysgeusia (5.6% vs. 65.2%, P<0.001), mucositis (16.7% vs. 52.2%, P=0.019), and nausea (11.1% vs. 56.5%, P=0.003). CONCLUSIONS The unique properties of PBRT allow greater normal tissue sparing without sacrificing target coverage when irradiating the ipsilateral head and neck. This dosimetric advantage seemingly translates into lower rates of acute treatment-related toxicity.

Proton radiography and proton computed tomography based on time-resolved dose measurements

We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time–dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (~100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is ~0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector.

Development and Clinical Implementation of a Universal Bolus to Maintain Spot Size During Delivery of Base of Skull Pencil Beam Scanning Proton Therapy

PURPOSE To report on a universal bolus (UB) designed to replace the range shifter (RS); the UB allows the treatment of shallow tumors while keeping the pencil beam scanning (PBS) spot size small. METHODS AND MATERIALS Ten patients with brain cancers treated from 2010 to 2011 were planned using the PBS technique with bolus and the RS. In-air spot sizes of the pencil beam were measured and compared for 4 conditions (open field, with RS, and with UB at 2- and 8-cm air gap) in isocentric geometry. The UB was applied in our clinic to treat brain tumors, and the plans with UB were compared with the plans with RS. RESULTS A UB of 5.5 cm water equivalent thickness was found to meet the needs of the majority of patients. By using the UB, the PBS spot sizes are similar with the open beam (P>.1). The heterogeneity index was found to be approximately 10% lower for the UB plans than for the RS plans. The coverage for plans with UB is more conformal than for plans with RS; the largest increase in sparing is usually for peripheral organs at risk. CONCLUSIONS The integrity of the physical properties of the PBS beam can be maintained using a UB that allows for highly conformal PBS treatment design, even in a simple geometry of the fixed beam line when noncoplanar beams are used.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements.

PURPOSE In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. METHODS An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. RESULTS Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. CONCLUSIONS Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.

Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries

The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in- and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields.

Comparison of prostate proton treatment planning technique, interfraction robustness, and analysis of single-field treatment feasibility

BACKGROUND This study compares target coverage robustness among proton therapy plans for prostate cancer patients treated with 2 laterally opposed fields delivered daily or, alternatively, every other day as single lateral fields, using uniform scanning (US), single-field uniform dose (SFUD), pencil beam scanning (PBS) optimized for uniform target coverage only, SFUD PBS optimized for target coverage and organs at risk (OAR) sparing (SFUD-opt), and intensity modulated proton therapy (IMPT). METHODS AND MATERIALS Ten prostate cancer patients treated with proton therapy underwent weekly verification computed tomographic (CT) scans. US, SFUD, SFUD-opt, and IMPT treatment plans were created and recalculated on weekly verification scans evaluating 2-field daily and single-field target coverage and OAR constraints. RESULTS The average (±standard deviation) planning target volume conformity index for US, SFUD, SFUD-opt, and IMPT clinical plans was 0.53 ± 0.06, 0.78 ± 0.05, 0.78 ± 0.04, and 0.78 ± 0.03, respectively. The average 2-field internal target volume (ITV) coverage was significantly higher for both US and SFUD when individually compared with SFUD-opt and IMPT. There was no significant difference between US and SFUD ITV coverage when comparing 2-field daily versus single-field daily delivery. The average single-field coverage was greatest using US and SFUD with 99% of the ITV being covered by 96.8% ± 0.9% and 96.7% ± 1.3%, respectively, compared with 95.5% ± 0.7% for SFUD-opt. There were no significant differences among the 4 plans regarding OAR dose constraints assessed. CONCLUSIONS Pencil beam scanning techniques are more conformal than US and, when optimized only for uniform target coverage from each field, can be equally as robust relative to anatomic interfraction variations for prostate cancer patients treated with a single field per day technique. The SFUD-opt and IMPT involve highly modulated pencil beam spots and may be less robust to daily interfraction anatomic variations.

The effect of anterior proton beams in the setting of a prostate-rectum spacer

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.

Hydrogel rectum-prostate spacers mitigate the uncertainties in proton relative biological effectiveness associated with anterior-oblique beams

Abstract Aim: Anterior-oblique (AO) proton beams can form an attractive option for prostate patients receiving external beam radiotherapy (EBRT) as they avoid the femoral heads. For a cohort with hydrogel prostate-rectum spacers, we asked whether it was possible to generate AO proton plans robust to end-of-range elevations in linear energy transfer (LET) and modeled relative biological effectiveness (RBE). Additionally we considered how rectal spacers influenced planned dose distributions for AO and standard bilateral (SB) proton beams versus intensity-modulated radiotherapy (IMRT). Material and methods: We studied three treatment strategies for 10 patients with rectal spacers: (A) AO proton beams, (B) SB proton beams and (C) IMRT. For strategy (A) dose and LET distributions were simulated (using the TOPAS Monte Carlo platform) and the McNamara model was used to calculate proton RBE as a function of LET, dose per fraction, and photon α/β. All calculations were performed on pretreatment scans: inter- and intra-fractional changes in anatomy/set-up were not considered. Results: For 9/10 patients, rectal spacers enabled generation of AO proton plans robust to modeled RBE elevations: rectal dose constraints were fulfilled even when the variable RBE model was applied with a conservative α/β = 2 Gy. Amongst a subset of patients the proton rectal doses for the planning target volume plans were remarkably low: for 2/10 SB plans and 4/10 AO plans, ≤10% of the rectum received ≥20 Gy. AO proton plans delivered integral doses a factor of approximately three lower than IMRT and spared the femoral heads almost entirely. Conclusion: Typically, rectal spacers enabled the generation of anterior beam proton plans that appeared robust to modeled variation in RBE. However, further analysis of day-to-day robustness would be required prior to a clinical implementation of AO proton beams. Such beams offer almost complete femoral head sparing, but their broader value relative to IMRT and SB protons remains unclear.

TU‐A‐204B‐02: On the Potential of CBCT for Range Verification in Proton Therapy

Purpose: We have investigated the potential use of cone beam CT(CBCT) for beam range verifications in proton therapy treatment, in addition to its primary role in geometric targeting. Specifically, we studied the intrinsic imaging variability of a CBCT and its effect on the water equivalent path length (WEPL) calculations, in the context of daily beam range verification/correction required for a recently proposed method of treating prostate using anterior fields. The current approach uses only lateral fields due to the lack of precise range control in patient. Materials and Methods: An anthropomorphic pelvic phantom was scanned using CBCT, in eight sessions on eight different days. In each session, the phantom was scanned twice, first at a standard position as determined by the room lasers, and then with a random shift of one centimeter in lateral directions. The Xio treatment planning system was used to perform the analysis. The average Hounsfield unit (HU) numbers for the water column in the rectal balloon was used to perform a linear calibration of the stopping power ratio, independently for each scan, as supported by the planning system. A number of WEPL values vertically from the anterior skin surface to the anterior surface of the water balloon were calculated on slices covering the region of the prostate, in relevance to a prostate treatment using an anterior field. Results: The HU number in the water column varied significantly even within the same CBCT. The average value also varied from day to day for up to 20 units. However, when these average values are used to calibrate the stopping power ratio, the variations in WEPL values along the anterior beam path are mostly within 2 mm. Conclusions: In‐room CBCT can be used in proton therapy to make online verification of protons range in patients with 2mm accuracy.

SU‐GG‐T‐471: Towards Range Guided Prostate Treatment Using an AP Field

Purpose:Proton treatment of prostate by anterior fields offers potential benefit in rectal sparing. However such treatment requires an accurate control of the beam range. We have recently proposed a method for in‐vivo range determination for prostate treatment by anterior fields, based on time‐resolved dose rate measurement. The method has been successfully tested against range shifting and range mixing of protons due to tissue inhomogeneity using simple geometric configurations in a water tank. In this study, we further evaluate the effectiveness of the method using a human pelvic phantom. Methods: A human pelvic phantom was used to mimic a real prostate treatment. The phantom was first CT scanned with a full bladder and a water balloon in the rectum. A treatment planningsoftware was used to compute the water equivalent path length (WEPL) between the phantom surface and the anterior inner surface of the rectum cavity, along the direction of an anterior beam. The phantom prostate was then irradiated using an anterior proton beam. A pinpoint ionization chamber was used to measure the time‐resolved dose rate function along the wall of the rectal cavity with spatial resolution of 0.25 mm. The obtained dose rate function were used to derive the corresponding WEPL values, and then compared with those calculated by the treatment planning system. Results: The time‐dependence of the measured dose rate functions showed limited deviations from those measured in a water tank, indicating a relatively low level of range mixing. This is consistent with the relatively mild tissue inhomogeneity along the beam path, despite the presence of the pubic bones. The discrepancy between the measured and calculated WEPL values is below 2mm. Conclusions: The time resolved dose rate method can be used, with reasonable accuracy, to control the beam range in prostate patient if treated by anterior fields.