A quantitative framework for patient-specific collision detection in proton therapy.

BACKGROUND: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired. PURPOSE: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions. METHODS: The patient's external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patient's orientation and each beam's gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the framework's analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm. RESULTS: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps. CONCLUSION: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry.

Building a precise machine-specific time structure of the spot and energy delivery model for a cyclotron-based proton therapy system.

Objective. We proposed an experimental approach to build a precise machine-specific beam delivery time (BDT) prediction and delivery sequence model for standard, volumetric, and layer repainting delivery based on a cyclotron accelerator system.Approach. Test fields and clinical treatment plans' log files were used to experimentally derive three main beam delivery parameters that impacted BDT: energy layer switching time (ELST), spot switching time, and spot drill time. This derived machine-specific model includes standard, volumetric, and layer repainting delivery sequences. A total of 103 clinical treatment fields were used to validate the model.Main results. The study found that ELST is not stochastic in this specific machine. Instead, it is actually the data transmission time or energy selection time, whichever takes longer. The validation showed that the accuracy of each component of the BDT matches well between machine log files and the model's prediction. The average total BDT was about (-0.74 ± 3.33)% difference compared to the actual treatment log files, which is improved from the current commercial proton therapy system's prediction (67.22%±26.19%).Significance. An accurate BDT prediction and delivery sequence model was established for an cyclotron-based proton therapy system IBA ProteusPLUS®. Most institutions could adopt this method to build a machine-specific model for their own proton system.

Beam-Specific Spot Guidance and Optimization for PBS Proton Treatment of Bilateral Head and Neck Cancers.

PURPOSE: A multi-field optimization (MFO) technique that uses beam-specific spot placement volumes (SPVs) and spot avoidance volumes (SAVs) is introduced for bilateral head and neck (H&N) cancers. These beam-specific volumes are used to guide the optimizer to consistently achieve optimal organ-at-risk (OAR) sparing with target coverage and plan robustness. MATERIALS AND METHODS: Implementation of this technique using a 4-beam, 5-beam, and variant 5-beam arrangement is discussed. The generation of beam-specific SPVs and SAVs derived from target and OARs are shown. The SPVs for select fields are further partitioned into optimization volumes for uniform dose distributions that resemble those of single-field optimization (SFO). A conventional MFO plan that does not use beam-specific spot placement guidance (MFOcon) and an MFO plan that uses only beam-specific SPV (MFOspv) are compared with current technique (MFOspv/sav), using both simulated scenarios and forward-calculated plans on weekly verification computed tomography (VFCT) scans. RESULTS: Dose distribution characteristics of the 4-beam, 5-beam, and variant 5-beam technique are demonstrated with discussion on OAR sparing. When comparing the MFOcon, MFOspv, and MFOspv/sav, the MFOspv/sav is shown to have superior OAR sparing in 9 of the 14 OARs examined. It also shows clinical plan robustness when evaluated by using both simulated uncertainty scenarios and forward-calculated weekly VFCTs throughout the 7-week treatment course. CONCLUSION: The MFOspv/sav technique is a systematic approach using SPVs and SAVs to guide the optimizer to consistently reach desired OAR dose values and plan robustness.

Auto-Trending daily quality assurance program for a pencil beam scanning proton system aligned with TG 224.

The Daily Quality Assurance (DQA) for a proton modality is not standardized. The modern pencil beam scanning proton system is becoming a trend and an increasing number of proton centers with PBS are either under construction or in planning. The American Association of Physicists in Medicine has a Task Group 224 report published in 2019 for proton modality routine QA. Therefore, there is a clinical need to explore a DQA procedure to meet the TG 224 guideline. The MatriXX PT and a customized phantom were used for the dosimetry constancy checking. An OBI box was used for imaging QA. The MyQA(TM) software was used for logging the dosimetry results. An in-house developed application was applied to log and auto analyze the DQA results. Another in-house developed program "DailyQATrend" was used to create DQA databases for further analysis. All the functional and easy determined tasks passed. For dosimetry constancy checking, the outputs for four gantry rooms were within ±3% with room to room baseline differences within ±1%. The energy checking was within ±1%. The spot location checking from the baseline was within 0.63 mm and the spot size checking from the baseline was within -1.41 ± 1.27 mm (left-right) and -0.24 ± 1.27 mm (in-out) by averaging all the energies. We have found that there was also a trend for the beam energies of two treatment rooms slowly going down (0.76% per month and 0.48 per month) after analyzing the whole data trend with linear regression. A DQA program for a PBS proton system has been developed and fully implemented into the clinic. The DQA program meets the TG 224 guideline and has web-based logging and auto treading functions. The clinical data show the DQA program is efficient and has the potential to identify the PBS proton system potential issue.

Proton pencil beam scanning treatment with feedback based voluntary moderate breath hold.

Introduction The aim of this article is to introduce a novel protocol for proton pencil beam scanning treatment with moderate deep inspiration breath hold (mDIBH) and report on our clinical implementation results. Methods Three computed tomography (CT) scannings to build the patient's anatomy model were performed during the patient's voluntary mDIBH. All 3 CT scans were used in the optimization during the treatment planning process. Both orthogonal kV imaging and cone-beam computed tomography (CBCT) were implemented for patient alignment with BH prior to the treatment. The BH CBCT images were analyzed for BH reproducibility and the virtual total dose (VTD) retrospectively. To find the VTD, a series of deformable image registrations (DIR) were performed between CBCT and pCT. The effect of the variation of lung density on the dose distribution was also analyzed in the study. Results The values of the mean, standard deviation, maximum, and minimum of the tumor location difference between the CBCT and pCT were 1.9, 1.6, 4.7, and 0.0 mm, respectively. The percentage difference in D99% of CTVs between VTD and the nominal plan was within 1.5%. Conclusions The feedback-based voluntary moderate BH proton PBS treatment was successfully performed in our clinic. This study shows that there is a potential to implement the BH treatment widely in proton centers.

Clinical examination of proton pencil beam scanning on a moving anthropomorphic lung phantom.

The objective of this study was to examine the use of proton pencil beam scanning for the treatment of moving lung tumors. A single-field uniform dose proton pencil beam scanning (PBS) plan was generated for the standard thorax phantom designed by the Imaging and Radiation Oncology Core (IROC) Houston QA Center. Robust optimization, including range and setup uncertainties as well as volumetric repainting, was used for the plan. Patient-specific quality assurance (QA) measurements were performed using both a water tank and a custom heterogeneous QA phantom. A custom moving phantom was used to find the optimal number of volumetric repainting. Both analytical and Monte Carlo (MC) algorithms were used for dose calculation and their accuracies were compared with actual measurements. A single ionization chamber, a 2-dimensional ionization chamber array, thermoluminescent dosimeters (TLDs), and films were used for dose measurements. The optimal number of volumetric repainting was found to be 4 times in our system. The mean dose overestimations on a moving target by analytical and MC algorithms based on a time-averaged computed tomography (CT) image of the phantom were found to be 4.8% and 2.4%, respectively. The mean gamma indexes for analytical and MC algorithms were 91% and 96%, respectively. The MC dose algorithm calculation was found to have a better agreement with measurements compared with the analytical algorithm. When treating moving lung tumors using proton PBS, the techniques of robust optimization, volumetric repainting, and MC dose calculation were found effective. Extra care needs to be taken when an analytical dose calculation algorithm is used.

Four-dimensional Plan Optimization for the Treatment of Lung Tumors Using Pencil-beam Scanning Proton Radiotherapy.

Purpose  This study aimed to evaluate the effectiveness of four-dimensional (4D) robust optimization for proton pencil-beam scanning (PBS) treatment of lung tumors. Patients and methods  In seven patients with lung cancer, proton beam therapy was planned using 4D robust optimization over 4D computed tomography (CT) data sets. The gross target volume (GTV) was contoured based on individual breathing phases, and a 5-mm expansion was used to generate the clinical target volume (CTV) for each phase. The 4D optimization was conducted directly on the 4D CT data set. The robust optimization settings included a CT Hounsfield unit (HU) uncertainty of 4% and a setup uncertainty of 5 mm to obtain the CTV. Additional target dose objectives such as those for the internal target volume (ITV) as well as the organ-at-risk (OAR) dose requirements were placed on the average CT. For comparison, three-dimensional (3D) robust optimization was also performed on the average CT. An additional verification 4D CT was performed to verify plan robustness against inter-fractional variations. Results  Target coverages were generally higher for 4D optimized plans. The difference was most pronounced for ITV V70Gy when evaluating individual breathing phases. The 4D optimized plans were shown to be able to maintain the ITV coverage at full prescription, while 3D optimized plans could not. More importantly, this difference in ITV V70Gy between the 4D and 3D optimized plans was also consistently observed when evaluating the verification 4D CT, indicating that the 4D optimized plans were more robust against inter-fractional variations. Less difference was seen between the 4D and 3D optimized plans in the lungs criteria: V5Gy and V20Gy. Conclusion  The proton PBS treatment plans optimized directly on the 4D CT were shown to be more robust when compared to those optimized on a regular 3D CT. Robust 4D optimization can improve the target coverage for the proton PBS lung treatments.

Robust Planning for a Patient Treated in Decubitus Position with Proton Pencil Beam Scanning Radiotherapy.

A challenging case was reported for a patient treated in decubitus position with proton pencil beam scanning. A regular robust plan with the consideration of the uncertainties of translational alignment and range accuracy cannot ensure the target coverage as revealed in two verification computed tomography (CT) scans during the first week of the treatment. The irreproducibility of daily alignment and anatomical variations in such a position is mainly due to patient's roll. To mitigate the interfractional effect on the target coverage, a novel robust optimization against the patient's angular setup uncertainties was implemented to improve the plan quality by introducing two artificial CT image sets by rolling the planning CT three degrees in both clockwise and counter-clockwise directions and adding them into robust optimization scenarios, which was shown to be an effective and simple way to mitigate target dose degradation with respect to interfractional variations. This method can be easily generalized and applied to other situations where angular variations in patient's setup can introduce large dosimetric effects. It is recommended that angularly robust optimization method should be integrated into the treatment planning system as an option particularly for patient's treatment subject to large angular variations, such as the one in the decubitus position reported here.

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

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/ß. 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/ß = 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.

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.

Using CBCT for pretreatment range check in proton therapy: a phantom study for prostate treatment by anterior-posterior beam.

This study explores the potential of cone-beam computed tomography (CBCT) for monitoring relative beam range variations due to daily changes in patient anatomy for prostate treatment by anterior proton beams. CBCT was used to image an anthropomorphic pelvic phantom, 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 after it was shifted by 10 mm translation randomly along one of the X, Y, or Z directions. The filling of the phantom bladder with water was not refreshed from day to day, inducing gradual change of the water-equivalent path length (WEPL) across the bladder. MIMvista (MIM) software was used to perform image registration and re-alignment of all the scans with the scan from the first session. The XiO treatment planning system was used to perform data analysis. It was found that, although the Hounsfield unit numbers in CBCT have substantially larger fluctuations than those in diagnostic CT, CBCT datasets taken for daily patient positioning could potentially be used to monitor changes in patient anatomy. The reproducibility of the WEPL, computed using CBCT along anterior-posterior (AP) paths across and around the phantom prostate, over a volume of 360 cc, is sufficient for detecting daily WEPL variations that are equal to or larger than 3 mm. This result also applies to CBCT scans of the phantom after it is randomly shifted from the treatment position by 10 mm. limiting the interest to WEPL variation over a specific path within the same CBCT slice, one can detect WEPL variation smaller than 1 mm. That is the case when using CBCT for tracking daily change of the WEPL across the phantom bladder that was induced by spontaneous change in the bladder filling due to evaporation. In summary, the phantom study suggests that CBCT can be used for monitoring day to day WEPL variations in a patient. The method can detect WEPL variation equal to or greater than 3 mm. The study calls for further investigation using the CBCT data from real patients. If confirmed with real patients' data, CBCT could become, in addition to patient setup, a standard tool for proton therapy pretreatment beam range check.

Lung cancer cell line screen links fanconi anemia/BRCA pathway defects to increased relative biological effectiveness of proton radiation.

PURPOSE: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. METHODS AND MATERIALS: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/µm). For comparison, 250-kVp X rays and (137)Cs γ-rays were used. To estimate the RBE of protons relative to (60)Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. RESULTS: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. CONCLUSIONS: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

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.

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.

Impact of intrafraction and residual interfraction effect on prostate proton pencil beam scanning.

PURPOSE: To quantitatively evaluate the impact of interplay effect and plan robustness associated with intrafraction and residual interfraction prostate motion for pencil beam scanning proton therapy. METHODS AND MATERIALS: Ten prostate cancer patients with weekly verification CTs underwent pencil beam scanning with the bilateral single-field uniform dose (SFUD) modality. A typical field had 10-15 energy layers and 500-1000 spots. According to their treatment logs, each layer delivery time was <1 s, with average time to change layers of approximately 8 s. Real-time intrafraction prostate motion was determined from our previously reported prospective study using Calypso beacon transponders. Prostate motion and beam delivering sequence of the worst-case scenario patient were synchronized to calculate the "true" dose received by the prostate. The intrafraction effect was examined by applying the worst-case scenario prostate motion on the planning CT, and the residual interfraction effect was examined on the basis of weekly CT scans. The resultant dose variation of target and critical structures was examined to evaluate the interplay effect. RESULTS: The clinical target volume (CTV) coverage was degraded because of both effects. The CTV D99 (percentage dose to 99% of the CTV) varied up to 10% relative to the initial plan in individual fractions. However, over the entire course of treatment the total dose degradation of D99 was 2%-3%, with a standard deviation of <2%. Absolute differences between SFUD, intensity modulate proton therapy, and one-field-per-day SFUD plans were small. The intrafraction effect dominated over the residual interfraction effect for CTV coverage. Mean dose to the anterior rectal wall increased approximately 10% because of combined residual interfraction and intrafraction effects, the interfraction effect being dominant. CONCLUSIONS: Both intrafraction and residual interfraction prostate motion degrade CTV coverage within a clinically acceptable level. One-field-per-day SFUD delivered twice is as robust as the bilateral SFUD plan treated daily over the course of treatment.

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.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT).

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as well as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients' average CT. All the plans delivered 50.4Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V18Gy), stomach (mean and V20Gy), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V18Gy), liver (mean dose), total bowel (V20Gy and mean dose), and small bowel (V15Gy absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.

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 time­dose 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.

Effect of intrafraction prostate motion on proton pencil beam scanning delivery: a quantitative assessment.

PURPOSE: To assess the dosimetric impact caused by the interplay between intrafraction prostate motion and the intermittent delivery of proton pencil beam scanning (PBS). METHODS AND MATERIALS: A cohort of 10 prostate patients was treated with PBS using a bilateral single-field uniform dose (SFUD) modality. Bilateral intensity-modulated proton therapy (IMPT) plans were generated for comparison. Because beam-on time in PBS was intermittent, the actual beam-on time was determined from treatment logs. Prostate motion was generalized according to real-time Calypso tracking data from our previously reported prospective photon trial. We investigated potential dose deviations by considering the interplay effect resulting from the worst-case scenario motion and the PBS delivery sequence. RESULTS: For both bilateral-field SFUD and IMPT plans, clinical target volume (CTV) D99% coverage was degraded <2% owing to prostate intrafraction motion when averaged over the course of treatment, but was >10% for the worst fraction. The standard deviation of CTV D99% distribution was approximately 1.2%. The CTV coverage of individual fields in SFUD plans degraded as time elapsed after the initial alignment, owing to prostate drift. Intensity-modulated proton therapy and SFUD demonstrated comparable results when bilateral opposed fields were used. Single-field SFUD plans that were repainted twice, which could reduce half of the treatment time, resulted in similar CTV coverage as bilateral-field plans. CONCLUSIONS: Intrafraction prostate motion affects the actual delivered dose to CTV; however, when averaged over the course of treatment, CTV D99% coverage degraded only approximately 2% even for the worst-case scenario. The IMPT plan results are comparable to those of the SFUD plan, and similar coverage can be achieved if treated by SFUD 1 lateral field per day when rescanning the field twice to shorten the treatment time and mitigate intrafraction motion.

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.