A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Stereotactic body proton therapy for early stage non-small cell lung cancer - Technical challenges and solutions: The MD Anderson experience.

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better treatment plan optimization and more accurate dose calculation. We expect to re-start the SBPT program, including for early stage NSCLC as well as for other disease sites soon after starting patient treatment at our new proton therapy center.

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma.

PURPOSE: We developed and tested a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources similar to those for regular intensity-modulated proton therapy (IMPT) plans and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries. METHODS: Our IMPAT planning method consists of a geometry-based energy selection step with major scanning spot contributions as inputs computed using ray-tracing and single-Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle such that each target voxel is covered by sufficient scanning spots as specified by the planner, with dose contributions above the specified threshold. Finally, IMPAT plans are generated by robustly optimizing scanning spots of the selected energy layers using a commercial proton treatment planning system (TPS). The IMPAT plan quality was assessed for four ependymoma patients. Reference three-field IMPT plans were created with similar planning objective functions and compared with the IMPAT plans. RESULTS: In all plans, the prescribed dose covered 95% of the clinical target volume (CTV) while maintaining similar maximum doses for the brainstem. While IMPAT and IMPT achieved comparable plan robustness, the IMPAT plans achieved better homogeneity and conformity than the IMPT plans. The IMPAT plans also exhibited higher relative biological effectiveness (RBE) enhancement than did the corresponding reference IMPT plans for the CTV in all four patients and brainstem in three of them. CONCLUSIONS: The proposed method demonstrated potential as an efficient technique for IMPAT planning and may offer a dosimetric benefit for patients with ependymoma or tumors in close proximity to critical organs. IMPAT plans created using this method had elevated RBE enhancement associated with increased linear energy transfer (LET) in both targets and abutting critical organs.

Cognitive and Imaging Differences After Proton and Photon Whole Brain Irradiation in a Preclinical Model.

PURPOSE: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities. METHODS AND MATERIALS: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with 18F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation. RESULTS: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation. CONCLUSIONS: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation.

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial.

PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

Transitioning from measurement-based to combined patient-specific quality assurance for intensity-modulated proton therapy.

OBJECTIVE: This study is part of ongoing efforts aiming to transit from measurement-based to combined patient-specific quality assurance (PSQA) in intensity-modulated proton therapy (IMPT). A Monte Carlo (MC) dose-calculation algorithm is used to improve the independent dose calculation and to reveal the beam modeling deficiency of the analytical pencil beam (PB) algorithm. METHODS: A set of representative clinical IMPT plans with suboptimal PSQA results were reviewed. Verification plans were recalculated using an MC algorithm developed in-house. Agreements of PB and MC calculations with measurements that quantified by the γ passing rate were compared. RESULTS: The percentage of dose planes that met the clinical criteria for PSQA (>90% γ passing rate using 3%/3 mm criteria) increased from 71.40% in the original PB calculation to 95.14% in the MC recalculation. For fields without beam modifiers, nearly 100% of the dose planes exceeded the 95% γ passing rate threshold using the MC algorithm. The model deficiencies of the PB algorithm were found in the proximal and distal regions of the SOBP, where MC recalculation improved the γ passing rate by 11.27% (p < 0.001) and 16.80% (p < 0.001), respectively. CONCLUSIONS: The MC algorithm substantially improved the γ passing rate for IMPT PSQA. Improved modeling of beam modifiers would enable the use of the MC algorithm for independent dose calculation, completely replacing additional depth measurements in IMPT PSQA program. For current users of the PB algorithm, further improving the long-tail modeling or using MC simulation to generate the dose correction factor is necessary. ADVANCES IN KNOWLEDGE: We justified a change in clinical practice to achieve efficient combined PSQA in IMPT by using the MC algorithm that was experimentally validated in almost all the clinical scenarios in our center. Deficiencies in beam modeling of the current PB algorithm were identified and solutions to improve its dose-calculation accuracy were provided.

Statistical evaluation of worst-case robust optimization intensity-modulated proton therapy plans using an exhaustive sampling approach.

PURPOSE: To assess the worst-case robust optimization IMPT plans with setup and range uncertainties and to test the hypothesis that the worst-case robust optimization strategies could cover most possible setup and range uncertainties in the real scenarios. METHODS: We analyzed the nominal and worst-case robust optimization IMPT plans of seven patients with head and neck cancer patients. To take uncertainties into account for the dose calculation, we performed a comprehensive simulation in which the dose was recalculated 625 times per given plan using Gaussian systematic setup and proton range uncertainties. Subsequently, based on the simulation results, we calculated the target coverage in all perturbation scenarios, as well as the ratios of target coverage located within the threshold of eight worst-case scenarios. We set the criteria for the optimized plan to be the ratios of 1) the dose delivered to 95% (D95%) of clinical target volumes 1 and 2 (CTV1 and CTV2) above 95% of the prescribed dose, and 2) the D95% of clinical target volume 3 (CTV3) above 90% of the prescribed dose in worst-case situations. RESULTS: The probability that the perturbed-dose indices of the CTVs in each scenario were within the worst-case scenario limits ranged from 89.51 to 91.22% for both the nominal and worst-case robust optimization IMPT plans. A quartile analysis showed that the selective robust optimization IMPT plans all had higher D95% values for CTV1, CTV2, and CTV3 than did the nominal IMPT plans. CONCLUSIONS: The worst-case strategy for robust optimization is adequately models and covers most of the setup and range uncertainties for the IMPT treatment of head and neck patients in our center.

Effect of setup and inter-fraction anatomical changes on the accumulated dose in CT-guided breath-hold intensity modulated proton therapy of liver malignancies.

PURPOSE: To evaluate the effect of setup uncertainties including uncertainties between different breath holds (BH) and inter-fractional anatomical changes under CT-guided BH with intensity-modulated proton therapy (IMPT) in patients with liver cancer. METHODS AND MATERIALS: This retrospective study considered 17 patients with liver tumors who underwent feedback-guided BH (FGBH) IMRT treatment with daily CT-on-rail imaging. Planning CT images were acquired at simulation using FGBH, and FGBH CT-on-rail images were also acquired prior to each treatment. Selective robust IMPT plans were generated using planning CT and re-calculated on each daily CT-on-rail image. Subsequently, the fractional doses were deformed and accumulated onto the planning CT according to the deformable image registration between daily and planning CTs. The doses to the target and organs at risk (OARs) were compared between IMRT, planned IMPT, and accumulated IMPT doses. RESULTS: For IMPT plans, the mean of D98% of CTV for all 17 patients was slightly reduced from the planned dose of 68.90 ±â€¯1.61 Gy to 66.48 ±â€¯1.67 Gy for the accumulated dose. The target coverage could be further improved by adjusting planning techniques. The dose-volume histograms of both planned and accumulated IMPT doses showed better sparing of OARs than that of the IMRT. CONCLUSIONS: IMPT with FGBH and CT-on-rail guidance is a robust treatment approach for liver tumor cases.

Reply to Comment on 'Linear energy transfer incorporated intensity modulated proton therapy optimization'.

In this reply we present additional description of our linear model for LET optimization in response to the comments by Dr Gorissen. We clarify that this model cannot guarantee global optimal solutions to the sum-of-fractions problem. Based on our data, it could be used to optimize LET efficiently while dose constraints are maintained.

Fixed- versus Variable-RBE Computations for Intensity Modulated Proton Therapy.

PURPOSE: To evaluate how using models of proton therapy that incorporate variable relative biological effectiveness (RBE) versus the current practice of using a fixed RBE of 1.1 affects dosimetric indices on treatment plans for large cohorts of patients treated with intensity modulated proton therapy (IMPT). METHODS AND MATERIALS: Treatment plans for 4 groups of patients who received IMPT for brain, head-and-neck, thoracic, or prostate cancer were selected. Dose distributions were recalculated in 4 ways: 1 with a fast-dose Monte Carlo calculator with fixed RBE and 3 with RBE calculated to 3 different models-McNamara, Wedenberg, and repair-misrepair-fixation. Differences among dosimetric indices (D02, D50, D98, and mean dose) for target volumes and organs at risk (OARs) on each plan were compared between the fixed-RBE and variable-RBE calculations. RESULTS: In analyses of all target volumes, for which the main concern is underprediction or RBE less than 1.1, none of the models predicted an RBE less than 1.05 for any of the cohorts. For OARs, the 2 models based on linear energy transfer, McNamara and Wedenberg, systematically predicted RBE >1.1 for most structures. For the mean dose of 25% of the plans for 2 OARs, they predict RBE equal to or larger than 1.4, 1.3, 1.3, and 1.2 for brain, head-and-neck, thorax, and prostate, respectively. Systematically lower increases in RBE are predicted by repair-misrepair-fixation, with a few cases (eg, femur) in which the RBE is less than 1.1 for all plans. CONCLUSIONS: The variable-RBE models predict increased doses to various OARs, suggesting that strategies to reduce high-dose linear energy transfer in critical structures should be developed to minimize possible toxicity associated with IMPT.

3D treatment planning system-Varian Eclipse for proton therapy planning.

The capabilities of the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) for proton therapy treatment planning are described. Various steps involved in the planning process to produce a 3-dimensional (3D) dose distribution both for the passive scattering and pencil beam scanning proton beam therapy are outlined. Mitigation of range and setup uncertainties through robust optimization is discussed. Use of verification plans for patient treatment field dosimetry quality assurance (QA) is presented. Limitations of the Eclipse TPS and future developments are discussed.

Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: To report the feasibility of conducting a randomized study to compare the toxicity and efficacy of stereotactic body radiation therapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk, medically inoperable, early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with medically inoperable NSCLC with high-risk features (centrally located or <5 cm T3 tumor or isolated lung parenchymal recurrences) were randomly assigned to SBRT or SBPT. Radiation dose was 50 Gy(relative biological effectiveness [RBE]) in 4 12.5-Gy(RBE) fractions prescribed to the planning target volume. Stereotactic body radiation therapy was given using 3-dimensional conformal radiation therapy or intensity modulated radiation therapy, and SBPT was given using passive scattering. Consistency in patient setup was ensured with on-board cone beam computed tomography for the SBRT group and with orthogonal X rays for the SBPT group. RESULTS: The study closed early owing to poor accrual, largely because of insurance coverage and lack of volumetric imaging in the SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50 Gy in 4 fractions were included for analysis (9 SBRT, 10 SBPT). At a median follow-up time of 32 months, median overall survival time was 28 months in the SBRT group and not reached in the SBPT group. Three-year overall survival was 27.8% and 90%, 3-year local control was 87.5% (8 of 9) and 90.0% (9 of 10), and 3-year regional control was 47.6% (5 of 9) and 90% (9 of 10) in the SBRT and SBPT groups, respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity. CONCLUSION: Poor accrual, due to lack of volumetric imaging and insurance coverage for proton therapy, led to early closure of the trial and precluded accurate assessment of efficacy and toxicity. Comparable maturity of 2 radiation therapy modalities, particularly on-board imaging, and better insurance coverage for SBPT should be considered for future studies.

Comparison of Monte Carlo and analytical dose computations for intensity modulated proton therapy.

To evaluate the effect of approximations in clinical analytical calculations performed by a treatment planning system (TPS) on dosimetric indices in intensity modulated proton therapy. TPS calculated dose distributions were compared with dose distributions as estimated by Monte Carlo (MC) simulations, calculated with the fast dose calculator (FDC) a system previously benchmarked to full MC. This study analyzed a total of 525 patients for four treatment sites (brain, head-and-neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD and Mean Dose) and a gamma-index analysis were utilized to evaluate the differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels with a dose larger than 10% of the maximum dose had a median larger than 98% for all sites. The median difference for all dosimetric indices for target volumes was less than 2% for all cases. However, differences for target volumes as large as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the median absolute dose difference was smaller than 2 Gy for all indices and cohorts. However, absolute dose differences as large as 10 Gy were found for some small volume organs in brain and head-and-neck patients. This analysis concludes that for a fraction of the patients studied, TPS may overestimate the dose in the target by as much as 10%, while for some OARs the dose could be underestimated by as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more accurate dose computations to improve target coverage and sparing of OARs in proton therapy.

Synchrotron-Based Pencil Beam Scanning Nozzle with an Integrated Mini-Ridge Filter: A Dosimetric Study to Optimize Treatment Delivery.

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS). Dosimetric characteristics in a homogenous water phantom were compared between plans with and without IMRF for a fixed spread-out Bragg peak width of 4 cm with distal ranges varying from 8 to 30 g/cm². Six clinical cases were then used to compare the plan quality between plans. The delivery efficiency was also compared between plans in both the phantom and the clinical cases. The Bragg peak width was increased by 0.18 cm at the lowest energy and by only about 0.04 cm at the highest energy. The IMRF increased the spot size (σ) by up to 0.1 cm at the lowest energy and by only 0.02 cm at the highest energy. For the phantom, the IMRF negligibly affected dose at high energies but increased the lateral penumbra by up to 0.12 cm and the distal penumbra by up to 0.06 cm at low energies. For the clinical cases, the IMRF slightly increased dose to the organs at risk. However, the beam delivery time was reduced from 18.5% to 47.1% for the lung, brain, scalp, and head and neck cases, and dose uniformities of target were improved up to 2.9% for these cases owing to the reduced minimum monitor unit effect. In conclusion, integrating a mini-ridge filter into a synchrotron nozzle is feasible for improving treatment efficiency without significantly sacrificing the plan quality.

Linear energy transfer incorporated intensity modulated proton therapy optimization.

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 µSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy.

PURPOSE: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. METHODS: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. RESULTS: The mean monthly equipment clinical availability for the spot scanning port in April 2012-March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012-August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%-40% of total treatment time for the total target volumes exceeding 200 cm(3), which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. CONCLUSIONS: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy.

PURPOSE: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. METHODS: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology, are assumed to be static. RESULTS: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. CONCLUSIONS: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.

Towards effective and efficient patient-specific quality assurance for spot scanning proton therapy.

An intensity-modulated proton therapy (IMPT) patient-specific quality assurance (PSQA) program based on measurement alone can be very time consuming due to the highly modulated dose distributions of IMPT fields. Incorporating independent dose calculation and treatment log file analysis could reduce the time required for measurements. In this article, we summarize our effort to develop an efficient and effective PSQA program that consists of three components: measurements, independent dose calculation, and analysis of patient-specific treatment delivery log files. Measurements included two-dimensional (2D) measurements using an ionization chamber array detector for each field delivered at the planned gantry angles with the electronic medical record (EMR) system in the QA mode and the accelerator control system (ACS) in the treatment mode, and additional measurements at depths for each field with the ACS in physics mode and without the EMR system. Dose distributions for each field in a water phantom were calculated independently using a recently developed in-house pencil beam algorithm and compared with those obtained using the treatment planning system (TPS). The treatment log file for each field was analyzed in terms of deviations in delivered spot positions from their planned positions using various statistical methods. Using this improved PSQA program, we were able to verify the integrity of the data transfer from the TPS to the EMR to the ACS, the dose calculation of the TPS, and the treatment delivery, including the dose delivered and spot positions. On the basis of this experience, we estimate that the in-room measurement time required for each complex IMPT case (e.g., a patient receiving bilateral IMPT for head and neck cancer) is less than 1 h using the improved PSQA program. Our experience demonstrates that it is possible to develop an efficient and effective PSQA program for IMPT with the equipment and resources available in the clinic.

Proton partial breast irradiation in the supine position: Treatment description and reproducibility of a multibeam technique.

PURPOSE: Proton-accelerated partial breast irradiation (APBI) is early in its developmental phase without standardized treatment parameters. We report an approach to multibeam proton APBI using a universally available supine setup and deliberate beam arrangement strategy to limit the total area of skin receiving a full dose while being robust for interfraction variation. METHODS AND MATERIALS: Thirty-three American Society for Radiation Oncology consensus-suitable/cautionary APBI candidates were treated using a passively scattered proton beam between 2010 and 2014 to 34 Gy relative biological effectiveness in 10 fractions twice daily. All patients were immobilized in a Vac-Lok cradle, typically with the arm down, and adducted to mound the breast and facilitate multiple, optimal en face beams. Radiopaque wires were placed on the surgical scar and 3 markers separate from the scar were placed elsewhere on the breast. All markers were used for each setup and removed before treatment. Marker displacement, wire rotation, and wire displacement were recorded from 10 random patients (100 orthogonal films). A 15-mm expansion was made to the tumor bed to obtain a clinical target volume, and followed by a 5-mm skin contraction and exclusion of the chest wall. A radial planning target volume margin of 5 mm was used. RESULTS: Across 100 pretreatment images, median displacement of 3 distinct skin set-up markers was 3, 4, and 3 mm. Displacement of the scar wire in the X and Y direction was 0 and 1 mm, respectively. Among 28 verification scans performed, only 1 resulted in adaptive planning because of the initial presence of an air pocket in the lumpectomy cavity that resolved spontaneously during treatment. CONCLUSIONS: APBI proton treatment using a supine approach was largely reproducible. Inter-fraction variation demonstrates 5-mm radial planning margins were adequate; however, outliers do occur and films should be reviewed critically and in real time. This technique is straightforward and could be used at any proton facility without the need for specialized equipment.