Stephen Avery

Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: Feasibility studies for range verification

The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents. The prototype CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data (2D) images of the PG emission were reconstructed. (1D) profiles were extracted from the PG images and compared to measured depth dose curves of the delivered proton pencil beams. The CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV proton beams at clinical beam currents. 2D images of the PG emission were reconstructed for single 150 MeV proton pencil beams as well as for a 5   ×   5 cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP) range were detectable on the 2D images. 1D profiles extracted from the PG images show that the distal falloff of the PG emission profile lined up well with the distal BP falloff. Shifts as small as 3 mm in the beam range could be detected from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the current CC prototype, a dose of 400 cGy was required to acquire adequate PG signal for 2D PG image reconstruction. It was possible to measure PG interactions with our prototype CC during delivery of proton pencil beams at clinical dose rates. Images of the PG emission could be reconstructed and shifts in the BP range were detectable. Therefore PGI with a CC for in vivo range verification during proton treatment delivery is feasible. However, improvements in the prototype CC detection efficiency and reconstruction algorithms are necessary to make it a clinically viable PGI system.

Proton beam characterization by proton-induced acoustic emission: simulation studies

Due to their Bragg peak, proton beams are capable of delivering a targeted dose of radiation to a narrow volume, but range uncertainties currently limit their accuracy. One promising beam characterization technique, protoacoustic range verification, measures the acoustic emission generated by the proton beam. We simulated the pressure waves generated by proton radiation passing through water. We observed that the proton-induced acoustic signal consists of two peaks, labeled α and γ, with two originating sources. The α acoustic peak is generated by the pre-Bragg peak heated region whereas the source of the γ acoustic peak is the proton Bragg peak. The arrival time of the α and γ peaks at a transducer reveals the distance from the beam propagation axis and Bragg peak center, respectively. The maximum pressure is not observed directly above the Bragg peak due to interference of the acoustic signals. Range verification based on the arrival times is shown to be more effective than determining the Bragg peak position based on pressure amplitudes. The temporal width of the α and γ peaks are linearly proportional to the beam diameter and Bragg peak width, respectively. The temporal separation between compression and rarefaction peaks is proportional to the spill time width. The pressure wave expected from a spread out Bragg peak dose is characterized. The simulations also show that acoustic monitoring can verify the proton beam dose distribution and range by characterizing the Bragg peak position to within ~1 mm.

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron

PURPOSE To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. METHODS An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. RESULTS The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. CONCLUSIONS The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.

Closing the Cancer Divide Through Ubuntu: Information and Communication Technology-Powered Models for Global Radiation Oncology

“The chance for a cure, the chance to live, should no longer remain an accident of geography” (1). This is one of the key messages in “Closing the cancer divide: A blueprint to expand access in low and middle income countries” (1). This article highlights the growing burden of global cancer disparities and makes a compelling case that the time for unified action to close this divide is now. There is growing consensus that information and communication technologies (ICTs) have tremendous potential to catalyze global health collaborations. Advanced ICTs can be used to leverage the recent major upsurge in global health interest into greater space-time flexible collaborative action against cancer and for enhancing greater effectiveness of existing global health initiatives. The recent call for greater action in closing the cancer divide through collaborations, including that in International Journal of Radiation, Oncology, Biology, Physics (IJROBP), inspired the 2015 Global Health Catalyst cancer summit, which brought together a unique combination of global oncology leaders, diaspora leaders, and ICT and palliative care experts, industry, nonprofits, and policy makers. The summit provided a forum for networking, knowledge sharing, and discussion of some of the emerging models for ICT-powered global health collaborations in radiation oncology care, research, and education, as well as avenues for complementary outreach, including engagement with the diaspora. This article summarizes the discussions and recommendations from the summit and highlights the emerging ICT-powered models for radiation oncology global health, avenues for greater outreach (ubuntu, a term signifying the idea that “I am because we are,” or human connectedness [see discussion below]) for greater impact and sustainability, as well as emerging areas for scaling up and increased action toward closing the cancer divide. At the primary level, a distressing illustration of the cancer divide can be seen in Africa, where most of Africa’s more than 2000 languages do not even have a word for cancer (2). Thus, in that geography, many people die painfully of cancer and, sadly, do not know it. In areas more familiar with cancer, a great lack of cancer prevention education or awareness of the importance of early detection contributes to over one third of preventable cancer deaths (3). This problem is further exacerbated by a culture of silence and strong social stigma associated with the disease (4); even young doctors do not want to specialize in oncology, a medical area that talks only about pain and death. The stigma also means that the overwhelming majority of patients only present late with the disease when it is too late to cure them; the ensuing deaths then further reinforce the stigma that cancer is essentially a death sentence. At a secondary level, the cancer divide is illustrated by the lack of capacity to manage patients once their disease is diagnosed, a problem inherent in poor health care systems. For example, approximately half of Africa’s 54 countries still have no radiation therapy services typically needed in the treatment of more than 50% of cancer patients (5). Limitations to radiation therapy in low- and middle-income countries (LMICs) include the number of radiation therapy centers, the number of treatment units, the critical shortage in health care workforce, the lack of safety regulatory infrastructure, and the perception that radiation therapy is a complex and expensive solution. Without greater investment and collaboration in radiation therapy services, this will only exacerbate the burden of cancer and make the cancer divide worse. Meanwhile, at the tertiary level, the cancer divide is appropriately captured by what has been called “the pain divide” (6). Here, many people dying with cancer do so in excruciating pain, due to a lack of basic pain medication and other palliative options. Such harrowing deaths with needless suffering bolster the physical and social trauma of cancer and the reason why many people in LMICs do not even want to talk about cancer. A word of African origin, which people do like to talk about, is ubuntu. Popularized worldwide by African Nobel Prize winners Desmond Tutu and Nelson Mandela, ubuntu signifies the idea that “I am because we are,” or human connectedness. This ethos rings particularly true in today’s hyperconnected world, where we all share in the bounty of the expanding internet or ICTs and where local health has become global health and vice versa. Ubuntu also represents an operating system underlying ICTs used for cloud computing, including in radiation oncology. The recent call for greater action in closing the cancer divide through collaborations (1, 7–9), including more recently in radiation oncology (8), inspired the 2015 Global Health Catalyst (GHC) cancer summit (10), which brought together a unique combination of global oncology leaders, industry, policy makers, and African diaspora leaders. Here the African diaspora refers to Africans settled outside of the African continent. Building on a recent publication (11), a central theme of the summit was the use of ICTs to catalyze high-impact international collaborations in cancer care, research, and education with Africa. This article summarizes the summit proceedings and highlights the emerging ICT-powered models for radiation oncology global health, avenues for greater partnership (ubuntu), and outreach beyond the traditional, as well as emerging areas for scaling up and increased action toward closing the cancer divide.

Analytical shielding calculations for a proton therapy facility

The University of Pennsylvania is building a proton therapy facility in collaboration with Walter Reed Army Medical Center. The proposed facility has four gantry rooms, a fixed beam room and a research room, and will use a cyclotron as the source of protons. In this study, neutron shielding considerations for the proposed proton therapy facility were investigated using analytical techniques and Monte Carlo simulated neutron spectra. Neutron spectra calculations were done using the GEANT4 (v6.2) simulation code for various materials: water, carbon, iron, nickel and tantalum to estimate the neutron production at proton beam energies of 100, 175 and 250 MeV. Dose equivalent calculations were performed using analytical methods at various critical points within the facility, by folding the GEANT4 produced neutron spectra with dose equivalent rate data from the National Council on Radiation Protection and Measurements (NCRP) Report #144.

Proton therapy in adjuvant treatment of gastric cancer: Planning comparison with advanced x-ray therapy and feasibility report

Abstract Background. Adjuvant chemoradiotherapy improves both overall- and relapse-free survival in patients with resected gastric cancer. However, this comes at the cost of increased treatment-related toxicity. Proton therapy (PT) has distinct dosimetric characteristics that may reduce dose to normal tissues, improving the therapeutic ratio. The purpose of this treatment planning study is to compare PT and intensity-modulated x-ray therapy (IMXT) in gastric cancer with regards to normal tissue sparing. Material and methods. The patient population consisted of resected gastric cancer patients treated at a single institution between 2008 and 2013. Patients who had undergone 4D CT simulation were replanned to the originally delivered doses (45–54 Gy in 25–30 daily fractions) using six-field photon IMXT and 2–3-field PT (double scattering-uniform scanning techniques). Results. Thirteen patients were eligible for the planning comparison. IMXT provided slightly higher homogeneity indices (median values 0.04 ± 0.01 vs. 0.07 ± 0.01, p = 0.03). PT resulted in significantly (p < 0.05) lower intermediate-low doses for all the normal tissues examined (small bowel V15 82 ml vs. 133 ml, liver mean doses Gy 11.9 vs. 14.4 Gy, left/right kidney mean doses 5/0.9 Gy vs. 7.8/3.1 Gy, heart mean doses 7.4 Gy vs. 9.5 Gy). The total energy deposited outside the target volume was significantly lower with PT (median integral dose 90.1 J vs. 129 J). Four patients were treated with PT: treatment was feasible and verifications scans showed that target coverage was robust. Conclusion. PT can contribute to normal tissue sparing in the adjuvant treatment of gastric cancer, with a potential benefit in terms of compliance to treatment, acute and late toxicities.

Hemithoracic Radiotherapy After Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma: A Dosimetric Comparison of Two Well-Described Techniques

Introduction: Extrapleural pneumonectomy (EPP) with adjuvant radiotherapy may be used to treat malignant pleural mesothelioma. Radiation pneumonitis, felt to be related to contralateral lung radiation dose, may affect patient mortality in this setting. Two standard therapeutic approaches currently used to deliver adjuvant radiotherapy were compared in this study: intensity modulation radiation treatment (IMRT) with a planned dose of 45 Gray (Gy) and a modified electron-photon technique delivering 54 Gy. Methods: Treatment plans of 10 mesothelioma patients who underwent EPP and hemithoracic IMRT to a total dose of 45 Gy were analyzed. Plans using a combination of opposed anterior posterior radiation fields and electron supplementation (electron-photon technique [EPT]) to a total dose of 54 Gy were then generated and compared with IMRT plans. Results: Dosimetric comparison revealed a significant reduction in contralateral lung dose with EPT versus IMRT, even with increased prescription dose used with EPT plans. Median heart and contralateral kidney doses were also significantly reduced with EPT versus IMRT. Dose coverage of planning target volume and doses to spinal cord, liver, and ipsilateral kidney were similar with use of the two techniques. Conclusions: Our data suggest that hemithoracic radiotherapy delivered after EPP using EPT may minimize dose to contralateral lung and other structures when compared with IMRT, without compromise of planning target volume coverage.

How proton pulse characteristics influence protoacoustic determination of proton-beam range: simulation studies

The unique dose deposition of proton beams generates a distinctive thermoacoustic (protoacoustic) signal, which can be used to calculate the proton range. To identify the expected protoacoustic amplitude, frequency, and arrival time for different proton pulse characteristics encountered at hospital-based proton sources, the protoacoustic pressure emissions generated by 150 MeV, pencil-beam proton pulses were simulated in a homogeneous water medium. Proton pulses with Gaussian widths ranging up to 200 μs were considered. The protoacoustic amplitude, frequency, and time-of-flight (TOF) range accuracy were assessed. For TOF calculations, the acoustic pulse arrival time was determined based on multiple features of the wave. Based on the simulations, Gaussian proton pulses can be categorized as Dirac-delta-function-like (FWHM < 4 μs) and longer. For the δ-function-like irradiation, the protoacoustic spectrum peaks at 44.5 kHz and the systematic error in determining the Bragg peak range is <2.6 mm. For longer proton pulses, the spectrum shifts to lower frequencies, and the range calculation systematic error increases (⩽ 23 mm for FWHM of 56 μs). By mapping the protoacoustic peak arrival time to range with simulations, the residual error can be reduced. Using a proton pulse with FWHM = 2 μs results in a maximum signal-to-noise ratio per total dose. Simulations predict that a 300 nA, 150 MeV, FWHM = 4 μs Gaussian proton pulse (8.0 × 10(6) protons, 3.1 cGy dose at the Bragg peak) will generate a 146 mPa pressure wave at 5 cm beyond the Bragg peak. There is an angle dependent systematic error in the protoacoustic TOF range calculations. Placing detectors along the proton beam axis and beyond the Bragg peak minimizes this error. For clinical proton beams, protoacoustic detectors should be sensitive to <400 kHz (for -20 dB). Hospital-based synchrocyclotrons and cyclotrons are promising sources of proton pulses for generating clinically measurable protoacoustic emissions.

Acoustic time-of-flight for proton range verification in water.

PURPOSE Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. METHODS Gaussian-like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 10(7) protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. RESULTS A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10(7) protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%-90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophones acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (-2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = - 4.5 mm and standard deviation = 2.0 mm. CONCLUSIONS Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beams position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.

Effects on the photon beam from an electromagnetic array used for patient localization and tumor tracking

One of the main components in a Calypso 4D localization and tracking system is an electromagnetic array placed above patients that is used for target monitoring during radiation treatment. The beam attenuation and beam spoiling properties of the Calypso electromagnetic array at various beam angles were investigated. Measurements were performed on a Varian Clinac iX linear accelerator with 6 MV and 15 MV photon beams. The narrow beam attenuation properties were measured under a field size of 1 cm×1 cm, with a photon diode placed in a cylindrical graphite buildup cap. The broad beam attenuation properties were measured under a field size of 10 cm×10 cm, with a 0.6 cc cylindrical Farmer chamber placed in a polystyrene buildup cap. Beam spoiling properties of the array were studied by measuring depth‐dose change from the array under a field size of 10 cm×10 cm cm in a water‐equivalent plastic phantom with an embedded Markus parallel plate chamber. Change in depth doses were measured with the array placed at distances of 2, 5, and 10 cm from the phantom surface. Narrow beam attenuation and broad beam attenuation from the array were found to be less than 2%–3% for both 6 MV and 15 MV beams at angles less than 40°, and were more pronounced at more oblique angles. Spoiling effects are appreciable at beam buildup region, but are insignificant at depths beyond dmax. Dose measurements in a QA phantom using patient IMRT and VMAT treatment plans were shown to have less than 2.5% dose difference with the Calypso array. The results indicate that the dose difference due to the placement of Calypso array is clinically insignificant. PACS number: 87.56.‐v