Measurement of the12C(p,n)12N reaction cross section below 150 MeV.

Objective. Proton therapy currently faces challenges from clinical complications on organs-at-risk due to range uncertainties. To address this issue, positron emission tomography (PET) of the proton-induced11C and15O activity has been used to provide feedback on the proton range. However, this approach is not instantaneous due to the relatively long half-lives of these nuclides. An alternative nuclide,12N (half-life 11 ms), shows promise for real-timein vivoproton range verification. Development of12N imaging requires better knowledge of its production reaction cross section.Approach. The12C(p,n)12N reaction cross section was measured by detecting positron activity of graphite targets irradiated with 66.5, 120, and 150 MeV protons. A pulsed beam delivery with 0.7-2 × 108protons per pulse was used. The positron activity was measured during the beam-off periods using a dual-head Siemens Biograph mCT PET scanner. The12N production was determined from activity time histograms.Main results. The cross section was calculated for 11 energies, ranging from 23.5 to 147 MeV, using information on the experimental setup and beam delivery. Through a comprehensive uncertainty propagation analysis, a statistical uncertainty of 2.6%-5.8% and a systematic uncertainty of 3.3%-4.6% were achieved. Additionally, a comparison between measured and simulated scanner sensitivity showed a scaling factor of 1.25 (±3%). Despite this, there was an improvement in the precision of the cross section measurement compared to values reported by the only previous study.Significance. Short-lived12N imaging is promising for real-timein vivoverification of the proton range to reduce clinical complications in proton therapy. The verification procedure requires experimental knowledge of the12N production cross section for proton energies of clinical importance, to be incorporated in a Monte Carlo framework for12N imaging prediction. This study is the first to achieve a precise measurement of the12C(p,n)12N nuclear cross section for such proton energies.

Feasibility of Monte Carlo dropout-based uncertainty maps to evaluate deep learning-based synthetic CTs for adaptive proton therapy.

BACKGROUND: Deep learning has shown promising results to generate MRI-based synthetic CTs and to enable accurate proton dose calculations on MRIs. For clinical implementation of synthetic CTs, quality assurance tools that verify their quality and reliability are required but still lacking. PURPOSE: This study aims to evaluate the predictive value of uncertainty maps generated with Monte Carlo dropout (MCD) for verifying proton dose calculations on deep-learning-based synthetic CTs (sCTs) derived from MRIs in online adaptive proton therapy. METHODS: Two deep-learning models (DCNN and cycleGAN) were trained for CT image synthesis using 101 paired CT-MR images. sCT images were generated using MCD for each model by performing 10 inferences with activated dropout layers. The final sCT was obtained by averaging the inferred sCTs, while the uncertainty map was obtained from the HU variance corresponding to each voxel of 10 sCTs. The resulting uncertainty maps were compared to the observed HU-, range-, WET-, and dose-error maps between the sCT and planning CT. For range and WET errors, the generated uncertainty maps were projected along the 90-degree angle. To evaluate the dose distribution, a mask based on the 5%-isodose curve was applied to only include voxels along the beam paths. Pearson's correlation coefficients were calculated to determine the correlation between the uncertainty maps and HUs, range, WET, and dose errors. To evaluate the dosimetric accuracy of synthetic CTs, clinical proton treatment plans were recalculated and compared to the pCTs RESULTS: Evaluation of the correlation showed an average of r = 0.92 ± 0.03 and r = 0.92 ± 0.03 for errors between uncertainty-HU, r = 0.66 ± 0.09 and r = 0.62 ± 0.06 between uncertainty-range, r = 0.64 ± 0.06 and r = 0.58 ± 0.07 between uncertainty-WET, and r = 0.65 ± 0.09 and r = 0.67 ± 0.07 between uncertainty and dose difference for DCNN and cycleGAN model, respectively. Dosimetric comparison for target volumes showed an average 3%/3 mm gamma pass rate of 99.76 ± 0.43 (DCNN) and 99.10 ± 1.27 (cycleGAN). CONCLUSION: The observed correlations between uncertainty maps and the various metrics (HU, range, WET, and dose errors) demonstrated the potential of MCD-based uncertainty maps as a reliable QA tool to evaluate the accuracy of deep learning-based sCTs.

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy.

PURPOSE: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients. METHODS: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs). The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined. RESULTS: The difference in the residual geometrical error dr (propagated CTVs - physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean < 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose. CONCLUSIONS: Setup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.

Clinical 3D/4D cumulative proton dose assessment methods for thoracic tumours with large motion.

PURPOSE: Despite the anticipated clinical benefits of intensity-modulated proton therapy (IMPT), plan robustness may be compromised due to its sensitivity to patient treatment uncertainties, especially for tumours with large motion. In this study, we investigated treatment course-wise plan robustness for intra-thoracic tumours with large motion comparing a 4D pre-clinical evaluation method (4DREM) to our clinical 3D/4D dose reconstruction and accumulation methods. MATERIALS AND METHODS: Twenty patients with large target motion (>10 mm) were treated with five times layered rescanned IMPT. The 3D-robust optimised plans were generated on the averaged planning 4DCT. Using multiple 4DCTs, treatment plan robustness was assessed on a weekly and treatment course-wise basis through the 3D robustness evaluation method (3DREM, based on averaged 4DCTs), the 4D robustness evaluation method (4DREM, including the time structure of treatment delivery and 4DCT phases) and 4D dose reconstruction and accumulation (4DREAL, based on fraction-wise information). RESULTS: Baseline target motion for all patients ranged from 11-17 mm. For the offline adapted course-wise dose assessment, adequate target dose coverage was found for all patients. The target volume receiving 95% of the prescription dose was consistent between methods with 16/20 patients showing differences < 1%. 4DREAL showed the highest target coverage (99.8 ± 0.6%, p < 0.001), while no differences were observed between 3DREM and 4DREM (99.3 ± 1.3% and 99.4 ± 1.1%, respectively). CONCLUSION: Our results show that intra-thoracic tumours can be adequately treated with IMPT in free breathing for target motion amplitudes up to 17 mm employing any of the accumulation methods. Anatomical changes, setup and range errors demonstrated a more severe impact on target coverage than motion in these patients treated with fractionated proton radiotherapy.

Technical note: Flat panel proton radiography with a patient specific imaging field for accurate WEPL assessment.

BACKGROUND: Proton radiography (PR) uses highly energetic proton beams to create images where energy loss is the main contrast mechanism. Water-equivalent path length (WEPL) measurements using flat panel PR (FP-PR) have potential for in vivo range verification. However, an accurate WEPL measurement via FP-PR requires irradiation with multiple energy layers, imposing high imaging doses. PURPOSE: A FP-PR method is proposed for accurate WEPL determination based on a patient-specific imaging field with a reduced number of energies (n) to minimize imaging dose. METHODS: Patient-specific FP-PRs were simulated and measured for a head and neck (HN) phantom. An energy selection algorithm estimated spot-wise the lowest energy required to cross the anatomy (Emin) using a water-equivalent thickness map. Starting from Emin, n was restricted to certain values (n = 26, 24, 22, …, 2 for simulations, n = 10 for measurements), resulting in patient-specific FP-PRs. A reference FP-PR with a complete set of energies was compared against patient-specific FP-PRs covering the whole anatomy via mean absolute WEPL differences (MAD), to evaluate the impact of the developed algorithm. WEPL accuracy of patient-specific FP-PRs was assessed using mean relative WEPL errors (MRE) with respect to measured multi-layer ionization chamber PRs (MLIC-PR) in the base of skull, brain, and neck regions. RESULTS: MADs ranged from 2.1 mm (n = 26) to 21.0 mm (n = 2) for simulated FP-PRs, and 7.2 mm for measured FP-PRs (n = 10). WEPL differences below 1 mm were observed across the whole anatomy, except at the phantom surfaces. Measured patient-specific FP-PRs showed good agreement against MLIC-PRs, with MREs of 1.3 ± 2.0%, -0.1 ± 1.0%, and -0.1 ± 0.4% in the three regions of the phantom. CONCLUSION: A method to obtain accurate WEPL measurements using FP-PR with a reduced number of energies selected for the individual patient anatomy was established in silico and validated experimentally. Patient-specific FP-PRs could provide means of in vivo range verification.

Daily dose evaluation based on corrected CBCTs for breast cancer patients: accuracy of dose and complication risk assessment.

OBJECTIVES: The goal of this study is to validate different CBCT correction methods to select the superior method that can be used for dose evaluation in breast cancer patients with large anatomical changes treated with photon irradiation. MATERIALS AND METHOD: Seventy-six breast cancer patients treated with a partial VMAT photon technique (70% conformal, 30% VMAT) were included in this study. All patients showed at least a 5 mm variation (swelling or shrinkage) of the breast on the CBCT compared to the planning-CT (pCT) and had a repeat-CT (rCT) for dose evaluation acquired within 3 days of this CBCT. The original CBCT was corrected using four methods: (1) HU-override correction (CBCTHU), (2) analytical correction and conversion (CBCTCC), (3) deep learning (DL) correction (CTDL) and (4) virtual correction (CTV). Image quality evaluation consisted of calculating the mean absolute error (MAE) and mean error (ME) within the whole breast clinical target volume (CTV) and the field of view of the CBCT minus 2 cm (CBCT-ROI) with respect to the rCT. The dose was calculated on all image sets using the clinical treatment plan for dose and gamma passing rate analysis. RESULTS: The MAE of the CBCT-ROI was below 66 HU for all corrected CBCTs, except for the CBCTHU with a MAE of 142 HU. No significant dose differences were observed in the CTV regions in the CBCTCC, CTDL and CTv. Only the CBCTHU deviated significantly (p < 0.01) resulting in 1.7% (± 1.1%) average dose deviation. Gamma passing rates were > 95% for 2%/2 mm for all corrected CBCTs. CONCLUSION: The analytical correction and conversion, deep learning correction and virtual correction methods can be applied for an accurate CBCT correction that can be used for dose evaluation during the course of photon radiotherapy of breast cancer patients.

Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach.

PURPOSE: In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated proton therapy (IMPT) using the expected normal tissue complication probability reduction (ΔNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT. MATERIALS AND METHODS: For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT. Both plans were robustly evaluated on weekly repeated 4DCTs and if target coverage degraded, replanning was performed. Target coverage was evaluated for complete treatment trajectories with and without replanning. The planned and accumulated mean lung dose (MLD) and mean heart dose (MHD) were additionally evaluated and translated into NTCP. RESULTS: Replanning in the clinic was performed more often for IMPT (15x) than would have been needed for VMAT (8x) (p = 0.11). Both adaptive treatments would have resulted in adequate accumulated target dose coverage. Replanning in the first week of treatment had most clinical impact, as anatomical changes resulting in insufficient accumulated target coverage were already observed at this stage. No differences were found in MLD between the planned dose and the accumulated dose. Accumulated MHD differed from the planned dose (p < 0.001), but since these differences were similar for VMAT and IMPT (1.0 and 1.5 Gy, respectively), the ΔNTCP remained unchanged. CONCLUSION: Following an adaptive clinical workflow, adequate target dose coverage and stable OAR doses with corresponding NTCPs was assured for both IMPT and VMAT.

Optimizing calibration settings for accurate water equivalent path length assessment using flat panel proton radiography.

OBJECTIVE: Proton range uncertainties can compromise the effectiveness of proton therapy treatments. Water equivalent path length (WEPL) assessment by flat panel detector proton radiography (FP-PR) can provide means of range uncertainty detection. Since WEPL accuracy intrinsically relies on the FP-PR calibration parameters, the purpose of this study is to establish an optimal calibration procedure that ensures high accuracy of WEPL measurements. To that end, several calibration settings were investigated. APPROACH: FP-PR calibration datasets were obtained simulating PR fields with different proton energies, directed towards water-equivalent material slabs of increasing thickness. The parameters investigated were the spacing between energy layers (ΔE) and the increment in thickness of the water-equivalent material slabs (ΔX) used for calibration. 30 calibrations were simulated, as a result of combining ΔE = 9, 7, 5, 3, 1 MeV and ΔX = 10, 8, 5, 3, 2, 1 mm. FP-PRs through a CIRS electron density phantom were simulated, and WEPL images corresponding to each calibration were obtained. Ground truth WEPL values were provided by range probing multi-layer ionization chamber simulations on each insert of the phantom. Relative WEPL errors between FP-PR simulations and ground truth were calculated for each insert. Mean relative WEPL errors and standard deviations across all inserts were computed for WEPL images obtained with each calibration. MAIN RESULTS: Large mean and standard deviations were found in WEPL images obtained with large ΔEvalues (ΔE = 9 or 7 MeV), for any ΔX. WEPL images obtained with ΔE ≤ 5 MeV and ΔX ≤ 5 mm resulted in a WEPL accuracy with mean values within ±0.5% and standard deviations around 1%. SIGNIFICANCE: An optimal FP calibration in the framework of this study was established, characterized by 3 MeV ≤ ΔE ≤ 5 MeV and 2 mm ≤ ΔX ≤ 5 mm. Within these boundaries, highly accurate WEPL acquisitions using FP-PR are feasible and practical, holding the potential to assist future online range verification quality control procedures.

Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.

PURPOSE: To ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning. MATERIALS AND METHODS: For 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.05 g/cm3 during plan optimization. The override was applied to the excursion of the diaphragm between exhale and inhale. Initial robustness evaluation was performed for plan acceptance (setup errors of 8 mm, range errors of ±3%), and subsequently, on all weekly repeated 4DCTs (setup errors of 2 mm, range errors of ±3%). Target coverage and hotspots were analyzed on the resulting voxel-wise minimum (Vwmin ) and voxel-wise maximum (Vwmax ) dose distributions. RESULTS: The nominal dose distributions were similar for both WDO and NDO plans. However, visual inspection of the Vwmax of the WDO plans showed hotspots behind the right diaphragm override region. For one patient, target coverage and hotspots improved by applying the diaphragm override. We found no differences in target coverage in the weekly evaluations between the two approaches. CONCLUSION: The diaphragm override approach did not result in a clinical benefit in terms of planning and interfractional robustness. Therefore, we do not see added value in employing this approach as a default option during robust optimization for IMPT planning in esophageal cancer.

Classification of various sources of error in range assessment using proton radiography and neural networks in head and neck cancer patients.

This study evaluates the suitability of convolutional neural networks (CNNs) to automatically process proton radiography (PR)-based images. CNNs are used to classify PR images impaired by several sources of error affecting the proton range, more precisely setup and calibration curve errors. PR simulations were performed in 40 head and neck cancer patients, at three different anatomical locations (fields A, B and C, centered for head and neck, neck and base of skull coverage). Field sizes were 26 × 26cm2for field A and 4.5 × 4.5cm2for fields B and C. Range shift maps were obtained by comparing an unperturbed reference PR against a PR where one or more sources of error affected the proton range. CT calibration curve errors in soft, bone and fat tissues and setup errors in the anterior-posterior and inferior-superior directions were simulated individually and in combination. A CNN was trained for each type of PR field, leading to three CNNs trained with a mixture of range shift maps arising from one or more sources of range error. To test the full/partial/wrong agreement between predicted and actual sources of range error in the range shift maps, exact, partial and wrong match percentages were computed for an independent test dataset containing range shift maps arising from isolated or combined errors, retrospectively. The CNN corresponding to field A showed superior capability to detect isolated and combined errors, with exact matches of 92% and 71% respectively. Field B showed exact matches of 80% and 54%, and field C resulted in exact matches of 77% and 41%. The suitability of CNNs to classify PR-based images containing different sources of error affecting the proton range was demonstrated. This procedure enables the detection of setup and calibration curve errors when they appear individually or in combination, providing valuable information for the interpretation of PR images.

Technical Note: 4D cone-beam CT reconstruction from sparse-view CBCT data for daily motion assessment in pencil beam scanned proton therapy (PBS-PT).

PURPOSE: The number of pencil beam scanned proton therapy (PBS-PT) facilities equipped with cone-beam computed tomography (CBCT) imaging treating thoracic indications is constantly rising. To enable daily internal motion monitoring during PBS-PT treatments of thoracic tumors, we assess the performance of Motion-Aware RecOnstructiOn method using Spatial and Temporal Regularization (MA-ROOSTER) four-dimensional CBCT (4DCBCT) reconstruction for sparse-view CBCT data and a realistic data set of patients treated with proton therapy. METHODS: Daily CBCT projection data for nine non-small cell lung cancer (NSCLC) patients and one SCLC patient were acquired at a proton gantry system (IBA Proteus® One). Four-dimensional CBCT images were reconstructed applying the MA-ROOSTER and the conventional phase-correlated Feldkamp-Davis-Kress (PC-FDK) method. Image quality was assessed by visual inspection, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the structural similarity index measure (SSIM). Furthermore, gross tumor volume (GTV) centroid motion amplitudes were evaluated. RESULTS: Image quality for the 4DCBCT reconstructions using MA-ROOSTER was superior to the PC-FDK reconstructions and close to FDK images (median CNR: 1.23 [PC-FDK], 1.98 [MA-ROOSTER], and 1.98 [FDK]; median SNR: 2.56 [PC-FDK], 4.76 [MA-ROOSTER], and 5.02 [FDK]; median SSIM: 0.18 [PC-FDK vs FDK], 0.31 [MA-ROOSTER vs FDK]). The improved image quality of MA-ROOSTER facilitated GTV contour warping and realistic motion monitoring for most of the reconstructions. CONCLUSION: MA-ROOSTER based 4DCBCTs performed well in terms of image quality and appear to be promising for daily internal motion monitoring in PBS-PT treatments of (N)SCLC patients.

Assessment of manual adjustment performed in clinical practice following deep learning contouring for head and neck organs at risk in radiotherapy.

BACKGROUND AND PURPOSE: Auto-contouring performance has been widely studied in development and commissioning studies in radiotherapy, and its impact on clinical workflow assessed in that context. This study aimed to evaluate the manual adjustment of auto-contouring in routine clinical practice and to identify improvements regarding the auto-contouring model and clinical user interaction, to improve the efficiency of auto-contouring. MATERIALS AND METHODS: A total of 103 clinical head and neck cancer cases, contoured using a commercial deep-learning contouring system and subsequently checked and edited for clinical use were retrospectively taken from clinical data over a twelve-month period (April 2019-April 2020). The amount of adjustment performed was calculated, and all cases were registered to a common reference frame for assessment purposes. The median, 10th and 90th percentile of adjustment were calculated and displayed using 3D renderings of structures to visually assess systematic and random adjustment. Results were also compared to inter-observer variation reported previously. Assessment was performed for both the whole structures and for regional sub-structures, and according to the radiation therapy technologist (RTT) who edited the contour. RESULTS: The median amount of adjustment was low for all structures (<2 mm), although large local adjustment was observed for some structures. The median was systematically greater or equal to zero, indicating that the auto-contouring tends to under-segment the desired contour. CONCLUSION: Auto-contouring performance assessment in routine clinical practice has identified systematic improvements required technically, but also highlighted the need for continued RTT training to ensure adherence to guidelines.

Validation of linear energy transfer computed in a Monte Carlo dose engine of a commercial treatment planning system.

The relative biological effectiveness (RBE) of protons is highly variable and difficult to quantify. However, RBE is related to the local ionization density, which can be related to the physical measurable dose weighted linear energy transfer (LETD). The aim of this study was to validate the LETD calculations for proton therapy beams implemented in a commercially available treatment planning system (TPS) using microdosimetry measurements and independent LETD calculations (Open-MCsquare (MCS)). The TPS (RayStation v6R) was used to generate treatment plans on the CIRS-731-HN anthropomorphic phantom for three anatomical sites (brain, nasopharynx, neck) for a spherical target (Ø = 5 cm) with uniform target dose to calculate the LETD distribution. Measurements were performed at the University Medical Center Groningen proton therapy center (Proteus Plus, IBA) using a µ +-probe utilizing silicon on insulator microdosimeters capable of detecting lineal energies as low as 0.15 keV µm-1 in tissue. Dose averaged mean lineal energy [Formula: see text] depth-profiles were measured for 70 and 130 MeV spots in water and for the three treatment plans in water and an anthropomorphic phantom. The [Formula: see text] measurements were compared to the LETD calculated in the TPS and MCS independent dose calculation engine. D · [Formula: see text] was compared to D · LETD in terms of a gamma-index with a distance-to-agreement criteria of 2 mm and increasing dose difference criteria to determine the criteria for which a 90% pass rate was accomplished. Measurements of D · [Formula: see text] were in good agreement with the D · LETD calculated in the TPS and MCS. The 90% passing rate threshold was reached at different D · LETD difference criteria for single spots (TPS: 1% MCS: 1%), treatment plans in water (TPS: 3% MCS: 6%) and treatment plans in an anthropomorphic phantom (TPS: 6% MCS: 1%). We conclude that D · LETD calculations accuracy in the RayStation TPS and open MCSquare are within 6%, and sufficient for clinical D · LETD evaluation and optimization. These findings remove an important obstacle in the road towards clinical implementation of D · LETD evaluation and optimization of proton therapy treatment plans. Novelty and significance The dose weighed linear energy transfer (LETD) distribution can be calculated for proton therapy treatment plans by Monte Carlo dose engines. The relative biological effectiveness (RBE) of protons is known to vary with the LETD distribution. Therefore, there exists a need for accurate calculation of clinical LETD distributions. Previous LETD validations have focused on general purpose Monte Carlo dose engines which are typically not used clinically. We present the first validation of mean lineal energy [Formula: see text] measurements of the LETD against calculations by the Monte Carlo dose engines of the Raystation treatment planning system and open MCSquare.

A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment.

BACKGROUND/OBJECTIVES: Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. METHODS: Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single-institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4-79.2 Gy) using PRT-only (n = 6) or combination PRT/intensity-modulated radiotherapy (IMRT) (n = 14). Quality-of-life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy - Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). RESULTS: Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow-up was 37 months. Feasibility endpoints were met. The 3-year local control and progression-free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end-of-treatment. CONCLUSIONS: We report favorable local control, survival, and toxicity following PRT.

Underrepresentation of Women and Minorities in the United States IR Academic Physician Workforce.

PURPOSE: To assess the United States interventional radiology (IR) academic physician workforce diversity and comparative specialties. METHODS: Public registries were used to assess demographic differences among 2012 IR faculty and fellows, diagnostic radiology (DR) faculty and residents, DR subspecialty fellows (pediatric, abdominal, neuroradiology, and musculoskeletal), vascular surgery and interventional cardiology trainees, and 2010 US medical school graduates and US Census using binomial tests with .001 significance level (Bonferroni adjustment for multiple comparisons). Significant trends in IR physician representation were evaluated from 1992 to 2012. RESULTS: Women (15.4%), blacks (2.0%), and Hispanics (6.2%) were significantly underrepresented as IR fellows compared with the US population. Women were underrepresented as IR (7.3%) versus DR (27.8%) faculty and IR fellows (15.4%) versus medical school graduates (48.3%), DR residents (27.8%), pediatric radiology fellows (49.4%), and vascular surgery trainees (27.7%) (all P < .001). IR ranked last in female representation among radiologic subspecialty fellows. Blacks (1.8%, 2.1%, respectively, for IR faculty and fellows); Hispanics (1.8%, 6.2%); and combined American Indians, Alaska Natives, Native Hawaiians, and Pacific Islanders (1.8%, 0) showed no significant differences in representation as IR fellows compared with IR faculty, DR residents, other DR fellows, or interventional cardiology or vascular surgery trainees. Over 20 years, there was no significant increase in female or black representation as IR fellows or faculty. CONCLUSIONS: Women, blacks, and Hispanics are underrepresented in the IR academic physician workforce relative to the US population. Given prevalent health care disparities and an increasingly diverse society, research and training efforts should address IR physician workforce diversity.

Proton pencil beam scanning for mediastinal lymphoma: treatment planning and robustness assessment.

BACKGROUND: Modern radiotherapy (RT) for lymphoma is highly personalized. While advanced imaging is largely employed to define limited treatment volumes, the use of proton pencil beam scanning (PBS) for highly conformal lymphoma RT is still in its infancy. Here, we assess the dosimetric benefits and feasibility of PBS for mediastinal lymphoma (ML). MATERIALS AND METHODS: Ten patients were planned using PBS for involved-site RT. The initial plans were calculated on the average four-dimensional computed tomography (4D-CT). PBS plans were compared with 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and proton double scattering (DS). In order to evaluate the feasibility of PBS and the plan robustness against inter- and intra-fractional uncertainties, the 4D dose was calculated on initial and verification CTs. The deviation of planned dose from delivered dose was measured. The same proton beamline was used for all patients, while another beamline with larger spots was employed for patients with large motion perpendicular to the beam. RESULTS: PBS provided the lowest mean lung dose (MLD) and mean heart dose (MHD) for all patients in comparison with 3D-CRT, IMRT, and DS. For eight patients, internal target volume (ITV) D98% was degraded by <3%; and the MLD and MHD deviated by <10% of prescription over the course of treatment when the PBS field was painted twice in each session. For one patient with target motion perpendicular to the beam (>5 mm), the degradation of ITV D98% was 9%, which was effectively mitigated by employing large spots. One patient exhibited large dose degradation due to pericardial effusion, which required replanning across all modalities. CONCLUSIONS: This study demonstrates that PBS plans significantly reduce MLD and MHD relative to 3D-CRT, IMRT, and DS and identifies requirements for robust free-breathing ML PBS treatments, showing that PBS plan robustness can be maintained with repainting and/or large spots.

Diversity by race, Hispanic ethnicity, and sex of the United States medical oncology physician workforce over the past quarter century.

PURPOSE: To assess the medical oncology (MO) physician workforce diversity by race, Hispanic ethnicity, and sex, with attention to trainees. METHODS: Public registries were used to assess 2010 differences among MO practicing physicians, academic faculty, and fellows; internal medicine (IM) residents; and the US population, using binomial tests with P < .001 significance adjusting for multiple comparisons. Significant changes in fellow representation from 1986 to 2011 were assessed. RESULTS: Female representation as MO fellows (45.0%) was significantly increased compared with faculty (22.4%) and practicing physicians (27.4%); was no different than IM residents (44.7%, P = .853); and increased significantly, by 1.0% per year. Women were significantly underrepresented as practicing physicians, faculty, and fellows compared with the US population (50.8%). Traditionally underrepresented minorities in medicine (URM) were significantly underrepresented as practicing physicians (7.8%), faculty (5.7%), and fellows (10.9%), versus US population (30.0%). Hispanic MO fellows (7.5%) were increased compared with faculty (3.9%) and practicing physicians (4.1%); Black fellows (3.1%) were no different than faculty (1.8%, P = .0283) or practicing physicians (3.5%, P = .443). When comparing MO fellows versus IM residents, there were no differences for American Indians/Alaska Natives/Native Hawaiians/Pacific Islanders (0.3%, 0.6%, respectively, P = .137) and Hispanics (7.5%, 8.7%, P = .139), unlike Blacks (3.1%, 5.6%, P < .001). There has been no significant change in URM representation, with negligible changes every 5 years for American Indians/Alaska Natives/Native Hawaiians/Pacific Islanders (-0.1%), Blacks (-0.3%), and Hispanics (0.3%). CONCLUSIONS: Female fellow representation increased 1% per year over the quarter century indicating historical gains, whereas URM diversity remains unchanged. For Blacks alone, representation as MO fellows is decreased compared with IM residents, suggesting greater disparity in MO training.

Current status of diversity by race, Hispanic ethnicity, and sex in diagnostic radiology.

PURPOSE: To assess the diversity of the U.S. diagnostic radiology physician workforce by race, Hispanic ethnicity, and sex in the context of the available pipeline of medical students. MATERIALS AND METHODS: Institutional review board evaluation and exemption were granted for the study, as primary data were obtained from publicly available registry sources, with no identifiable private or protected information. Publicly available American Medical Association, American Association of Medical Colleges, and U.S. census registries were used to assess differences for 2010 among diagnostic radiology practicing physicians, academic faculty, residents, subspecialty trainees, residency applicants, medical school graduates, and U.S. population by using binomial tests; with adjustment for multiple comparisons among different groups, differences with P < .001 were considered significant. Significant differences in diagnostic radiology resident representation were evaluated for academic years 2003-2004 to 2010-2011 and for 2010, compared among the 20 largest residency training programs. RESULTS: Females and traditionally underrepresented minorities in medicine (URM)-blacks, Hispanics, American Indians, Alaskan Natives, Native Hawaiians, and Pacific Islanders (AI/AN/NH/PI)-are underrepresented as practicing physicians (23.5% and 6.5%, respectively), faculty (26.1%, 5.9%), and diagnostic radiology residents (27.8%, 8.3%), compared with the U.S. population (50.8%, 30.0%) (all P < .001). Although they are increased in percentage as residents compared with practicing physicians, females and URMs remain underrepresented at the resident trainee level, compared with their proportions as medical school graduates (48.3%, 15.3%, respectively). During the past 8 years, there was no significant increase in female or URM resident (all P > .01) representation, suggesting no dramatic change in future representation as practicing physicians. Moreover, diagnostic radiology ranks 17th in female and 20th in URM representation among the 20 largest residency training specialties. CONCLUSION: Females and URM remain underrepresented in the diagnostic radiology physician workforce despite an available medical student pipeline. Given prevalent health care disparities and an increasingly diverse society, future research and training efforts should address increasing resident diversity with program directors and department chairs.

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.

Upfront androgen deprivation therapy with salvage radiation may improve biochemical outcomes in prostate cancer patients with post-prostatectomy rising PSA.

PURPOSE: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. METHODS AND MATERIALS: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at the University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. RESULTS: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores ≤7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). CONCLUSIONS: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.