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McDonough, James

Publications and source records attributed to McDonough, James.

Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy

Purpose: To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode. Methods and Materials: A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. Results: In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were −0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and −0.4 ± 0.9 mm for the vertex field. Conclusions: This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

First Clinical Investigation of Cone Beam Computed Tomography and Deformable Registration for Adaptive Proton Therapy for Lung Cancer

Purpose: An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning. Methods and Materials: The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface. Results: The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology. Conclusions: A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Proposed linear energy transfer areal detector for protons using radiochromic film

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

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 D{sub 99} (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 D{sub 99} 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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Supine Craniospinal Irradiation Using a Proton Pencil Beam Scanning Technique Without Match Line Changes for Field Junctions

Purpose: To propose and validate a craniospinal irradiation approach using a proton pencil beam scanning technique that overcomes the complexity of the planning associated with feathering match lines. Methods and Materials: Ten craniospinal irradiation patients had treatment planned with gradient dose optimization using the proton pencil beam scanning technique. The robustness of the plans was evaluated by shifting the isocenter of each treatment field by ±3 mm in the longitudinal direction and was compared with the original nonshifted plan with metrics of conformity number, homogeneity index, and maximal cord doses. An anthropomorphic phantom study using film measurements was carried out on a plan with 5-cm junction length. To mimic setup errors in the phantom study, fields were recalculated with isocenter shifts of 1, 3, 5, and 10 mm longitudinally, and compared with the original plans and measurements. Results: Uniform dose coverage to the entire target volumes was achieved using the gradient optimization approach with averaged junction lengths of 6.7 ± 0.5 cm. The average conformity number and homogeneity index equaled 0.78 ± 0.03 and 1.09 ± 0.01, respectively. Setup errors of 3 mm per field (6 mm in worst-case scenario) caused on average 4.6% lower conformity number 2.5% higher homogeneity index and maximal cord dose of 4216.1 ± 98.2 cGy. When the junction length was 5 cm or longer, setup errors of 6 mm resulted in up to 12% dosimetric deviation. Consistent results were reached between film measurements and planned dose profiles in the junction area. Conclusions: Longitudinal setup errors directly reduce the dosimetric accuracy of the proton craniospinal irradiation treatment with matched proton pencil beam scanning fields. The reported technique creates a slow dose gradient in the junction area, which makes the treatment more robust to longitudinal setup errors compared to conventional feathering methods.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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) D{sub 99}% 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 D{sub 99}% 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 D{sub 99}% 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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A clinically feasible method for the detection of potential collision in proton therapy

Purpose: Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. Methods: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. Results: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning phase. Conclusions: The authors developed a fast and clinically feasible patient-specific collision detection program for proton therapy based on a ray casting algorithm. If incorporated during the treatment planning phase it may lead to improved clinical efficiency. This methodology could also be applied to patient collision detection in photon therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Predicted Rates of Secondary Malignancies From Proton Versus Photon Radiation Therapy for Stage I Seminoma

Purpose: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. Methods and Material: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. Results: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). Conclusions: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗