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The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy.

Introduction Ultra-high dose rate (FLASH) radiotherapy has become a popular research topic with the potential to reduce normal tissue toxicities without losing the benefit of tumor control. The development of FLASH proton pencil beam scanning (PBS) delivery requires accurate dosimetry despite high beam currents with correspondingly high ionization densities in the monitoring chamber. In this study we characterized a newly designed high-resolution position sensing transmission ionization chamber with a purpose-built multi-channel electrometer for both conventional and FLASH dose rate proton radiotherapy. Methods The dosimetry and positioning accuracies of the ion chamber were fully characterized with a clinical scanning beam. On the FLASH proton beamline, the cyclotron output current reached up to 350 nA with a maximum energy of 226.2MeV, with 210±3 nA nozzle pencil beam current. The ion recombination effect was characterized under various bias voltages up to 1000 V and different beam intensities. The charge collected by the transmission ion chamber was compared with the measurements from a Faraday cup. Results Cross-calibrated with an Advanced Markus chamber (PTW, Freiburg, Germany) in a uniform PBS proton beam field at clinical beam setting, the ion chamber calibration was 38.0 and 36.7 GyE·mm2 /nC at 100 and 226.2 MeV, respectively. The ion recombination effect increased with larger cyclotron current at lower bias voltage while remaining ≤0.5±0.5% with ≥200 V of bias voltage. Above 200 V, the normalized ion chamber readings demonstrated good linearity with the mass stopping power in air for both clinical and FLASH beam intensities. The spot positioning accuracy was measured to be 0.10±0.08 mm in two orthogonal directions. Conclusion We characterized a transmission ion chamber system under both conventional and FLASH beam current densities and demonstrated its suitability for use as a proton pencil beam dose and spot position delivery monitor under FLASH dose rate conditions.

Objective: Proton therapy offers an advantageous dose distribution compared to the photon therapy, since it deposits most of the energy at the end of range, namely the Bragg peak (BP). Protoacoustic technique was developed to in vivo determine the BP locations. However, it requires large dose delivery to the tissue to obtain an averaged acoustic signal with a sufficient signal to noise ratio (SNR), which is not suitable in clinics. We propose a deep learning-based technique to acquire denoised acoustic signals and reduce BP range uncertainty with much lower doses. Approach: Three accelerometers were placed on the distal surface of a cylindrical polyethylene (PE) phantom to collect protoacoustic signals. In total 512 raw signals were collected at each device. Device-specific stack autoencoder (SAE) denoising models were trained to denoise the input signals, which were generated by averaging 1, 2, 4, 8, 16, or 32 raw signals. Both supervised and unsupervised learning training strategies were tested for comparison. Mean squared error (MSE), signal-to-noise ratio (SNR) and the Bragg peak (BP) range uncertainty were used for model evaluation. Main results: After SAE denoising, the MSE was substantially reduced, and the SNR was enhanced. Overall, the supervised SAEs outperformed the unsupervised SAEs in BP range verification. For the high accuracy detector, it achieved a BP range uncertainty of 0.20 +/- 3.44 mm by averaging over 8 raw signals, while for the other two low accuracy detectors, they achieved the BP uncertainty of 1.44 +/- 6.45 mm and -0.23 +/- 4.88 mm by averaging 16 raw signals, respectively. Significance: We have proposed a deep learning based denoising method to enhance the SNR of protoacoustic measurements and improve the accuracy in BP range verification, which greatly reduces the dose and time for potential clinical applications., Comment: 15 pages, 5 figures

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit experimental and Monte Carlo (MC) simulation data acquired with the Polaris-J Compton Camera (CC) prototype. The differences between the proton beam range (R

Purpose Recent studies suggest that ultrahigh-dose-rate, “FLASH,” electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. Methods and Materials Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation. Results The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 ± 9 Gy per second and 0.9 ± 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation. Conclusions We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

Purpose/Objective(s): The COVID-19 pandemic has direct and indirect impact on patients with cancer. Low- and middle-income regions, especially sub-Saharan Africa, are especially vulnerable to a negative impact on cancer resources and outcomes. We report the initial indirect impact of COVID-19 on cancer care in the sub-Saharan Africa region approximately 14 months into the pandemic. Materials/Methods: At the start of the pandemic, we created a consortium of African and North American cancer centers and NGOs for the distribution of factual and timely information and data on COVID-19 and cancer care. A survey was distributed to consortium members and other colleagues from the sub-Saharan Africa region to understand the impact of COVID-19 in cancer care resources. Survey respondents represent cancer experts from 8 centers in Ghana, Nigeria, Kenya, Ethiopia, South Africa, Rwanda, and Zimbabwe. Results: All sites report SARS-COv-2 transmission amongst cancer patients and staff. A total of 48 staff developed COVID-19 infection with one site reporting a single death. Additionally, 62.5% of sites report loss of oncology physician or nursing staff due to redeployment for COVID-19 care resulting in minimal (20%), moderate (60%), or other (20%) impact on cancer care. All 8 sites report a government mandated lockdown with a median duration of 2.3 months (IQR.9-4.2 months). Impact of the lockdown on cancer care was reported as none (12.5%), minimal (12.5%), moderate (50%) and severe (25%). Additionally, we surveyed the impact of COVID-19 on resources in radiation, medical and surgical oncology services. A total of 25% of responders reported decreases in radiation resources while 37.5% reported changes in medical and surgical oncology resources. For radiation oncology, the most common impact was access to CT imaging for 3D-conformal planning (25%), access to brachytherapy (12.5%), and medical physics support (12.5%). For medical oncology, the most frequent impact was access to chemotherapy (37.5%) and blood products (12.5%), and loss of oncology ward space (12.5%). The most frequent impact for surgical oncology was access to operating rooms (37.5%), ventilators (12.5%), anesthesia (25%), blood products (25%), and other supply chain issues (25%). Of centers who reported impact on cancer care, severity of impact was none (50%) and moderate (50%) for radiation oncology;mild (25%) and moderate (75%) for medical oncology;and moderate (75%) and severe (25%) for surgical oncology. Conclusion: Our survey identified diffuse impact of COVID-19 on all facets of cancer care across sub-Saharan Africa. Based on physician assessment of impact, the discipline of surgical oncology may be impacted the greatest. Additional studies measuring the impact of COVID-19 on cancer outcomes are ongoing.

Radiotherapy (RT) is an effective method of cancer treatment, but like any other method of cancer treatment, there are inherent limitations. While technological advances and a growing understanding of its biological effects have improved its results dramatically, the use of RT is still limited to certain patient populations and by normal tissue toxicities. The harmful side effects of treating patients with radiation can offset its therapy benefits, limiting its use in certain cases. Phyto, or plant-based, medicines offer a way to add to radiation treatment, while also protecting patients from its toxic side effects. Phytomedicines such as cannabinoids (CBD) and bitter melon extract have demonstrated therapeutic properties, including the ability to activate apoptotic death in cancer cells, diminish tumor progression, and generally decrease the incidence of several cancer types. In addition, herbal drugs have been shown to be powerful antioxidants with the ability to decrease toxicity of RT without the adverse side effects found in synthetic drugs. Furthermore, a number of phytomedicines have been shown to mitigate hypoxic conditions within the tumor microenvironment, creating a more radiosensitive disease and preventing tumorigenesis. The purpose of this article is to examine the merits and demerits of employing phytomedicines during RT. Results from studies that have tested the effects of combining radiotherapy with supplemental herbal treatment are discussed along with perspectives on where additional research is needed to advance “Phytoradiotherapy”. Overall, experimental evidence points to the fact that phytomedicines have significant potential to enhance RT, with need for cross-disciplinary collaborations to establish optimal dosing combinations with evidence-base for clinical translation.

Protoacoustics, the measurement of the pressure waves emitted by thermal expansion resulting from proton dose deposition, may be used to obtain the depth of the Bragg-peak (BP) by measuring the time-of-flight of the pressure wave. However, using the method in the clinic has a drawback since numerous measured signals were averaged to identify the accurate signal peak from the indistinguishable noises. We proposed a wavelet-based denoising method to significantly reduce noise in collected protoacoustic signals and improve the BP identification accuracy with fewer signal averages. The average 1024 signal, which has been used in the published study, was used as the reference to identify the accurate acoustic location. We used Daubechies (db) 4 wavelet transform to decompose the collected signals to recover the useful protoacoustic signals. Our approach was able to identify the BP signal up to the average 8 signals that correspond to the dose (

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.

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient’s basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.

This work describes all stages of development (setup, optimization, performance, and first experimental measurements) of an acoustic sensor that can be used for range monitoring and dosimetry of clinical radiotherapy beams. The detection device consists of an ultrasonic transducer, a combination of preamplifiers and differential amplifiers with filtered outputs and a digital oscilloscope. Simulations of the experimental setup were carried out to study the optimal measurement geometry and choice of transducer. The dose distributions were calculated with the Monte Carlo code FLUKA, while the acoustic simulations were performed with the analytical wave transport code k-Wave. The temporal profiles of the dose pulses, in the order of mu s, were measured with a scintillating crystal coupled to a photomultiplier and used as input for the acoustic simulation. Measurements were performed in a Cyberknife (TM) radiosurgery beam and a TrueBeam unit. A lead block was submerged in water and placed partially or totally in the irradiation field in order to increase the acoustic signal. Photoacoustic signals were detected with both beams with the expected shape and time-delay, after the frequency response of the detection system was taken into account. The proposed setup can detect photoacoustic signals originating from the penumbra of the treatment fields after being processed with the appropriate image analysis tools.

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 × 107 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 × 107 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 hydrophone’s 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 beam’s 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.

“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.

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

In vivo range verification in patients is determined to be crucial to utilize the full potential of proton radiotherapy Parodi et al, (Mod Phys Lett A, 30, 1540025, 2015, [1]). In this work we study the detection of acoustic waves generated by a clinical photon beam. Since the dose-acoustic effect is similar in photons and protons, the results of this work can be further extrapolated to proton beams Jones et al, (Phys Med Biol, 59, (21), 6549, 2014, [2]).

Purpose: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. Methods: For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. Results: The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. Conclusion: On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient. (C) 2018 Elsevier B.V. All rights reserved.

Structure functions, as measured in lepton-nucleon scattering, have proven to be very useful in studying the partonic dynamics within the nucleon. However, it is experimentally difficult to separately determine the longitudinal and transverse structure functions, and consequently there are substantially less data available in particular for the longitudinal structure function. Here, we present separated structure functions for hydrogen and deuterium at low four-momentum transfer squared, Q2

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4's effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4-/- murine and human CD34+-derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT.

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 emissionsgenerated 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 generatedproton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissionsgenerated 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 emissionsgenerated 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 vivoproton range verification and patient monitoring.

We tested the ability of a single Compton camera (CC) to produce 3-dimensional (3D) images of prompt gammas (PGs) emitted during the irradiation of a tissue-equivalent plastic phantom with proton pencil beams for clinical doses delivered at clinical dose rates. PG measurements were made with a small prototype CC placed at three different locations along the proton beam path. We evaluated the ability of the CC to produce images at each location for two clinical scenarios: (1) the delivery of a single 2 Gy pencil beam from a hypo-fractionated treatment (~9 × 108 protons), and (2) a single pencil beam from a standard treatment (~1 × 108 protons). Additionally, the data measured at each location were combined to simulate measurements with a larger scale, clinical CC and its ability to image shifts in the Bragg peak (BP) range for both clinical scenarios. With our prototype CC, the location of the distal end of the BP could be seen with the CC placed up to 4 cm proximal or distal to the BP distal falloff. Using the data from the simulated full scale clinical CC, 3D images of the PG emission were produced with the delivery of as few as 1 × 108 protons, and shifts in the proton beam range as small as 2 mm could be detected for delivery of a 2 Gy spot. From these results we conclude that 3D PG imaging for proton range verification under clinical beam delivery conditions is possible with a single CC.

Acoustic waves are induced via the thermoacoustic effect in objects exposed to a pulsed beam of ionizing radiation. This phenomenon has interesting potential applications in both radiotherapy dosimetry and treatment guidance as well as low-dose radiological imaging. After initial work in the field in the 1980s and early 1990s, little research was done until 2013 when interest was rejuvenated, spurred on by technological advances in ultrasound transducers and the increasing complexity of radiotherapy delivery systems. Since then, many studies have been conducted and published applying ionizing radiation-induced acoustic principles into three primary research areas: Linear accelerator photon beam dosimetry, proton therapy range verification, and radiological imaging. This review article introduces the theoretical background behind ionizing radiation-induced acoustic waves, summarizes recent advances in the field, and provides an outlook on how the detection of ionizing radiation-induced acoustic waves can be used for relative and in vivo dosimetry in photon therapy, localization of the Bragg peak in proton therapy, and as a low-dose medical imaging modality. Future prospects and challenges for the clinical implementation of these techniques are discussed.

Purpose: Several studies have recently shown that the characteristics of prompt gamma (PG) rays emitted during proton radiation therapy are beneficial for verifying proton beam range during treatment delivery. Since PG rays are produced instantaneously upon the proton beam delivery, the viability of in vivo beam range verification using PG rays depends greatly on the design optimization of not only intrinsically highly efficient detectors, but also detector location around the beam to maximize detection efficiency. The purpose of this study is to characterize angular dependence of the PG detection rates as a function of proton beam energy to help develop the design of clinically feasible detectors. Materials and Methods: In this study as a part of the long-term goal of developing a clinically feasible multistage Compton camera, we performed a Monte Carlo–based study of the detector response in a water phantom over the clinical range of beam energies, 50 to 200 MeV, and characterized PG emission s...

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

The Small Animal Radiation Research Platform (SARRP) is a commercially available platform designed to deliver conformal, image-guided radiation to small animals using a dual-anode kV x-ray source. At the University of Pennsylvania, a free-standing 2 m3 enclosure was designed to shield the SARRP according to federal code regulating cabinet x-ray systems. The initial design consisted of 4.0-mm-thick lead for all secondary barriers and proved wholly inadequate. Radiation levels outside the enclosure were 15 times higher than expected. Additionally, the leakage appeared to be distributed broadly within the enclosure, so concern arose that a subject might receive significant doses outside the intended treatment field. Thus, a detailed analysis was undertaken to identify and block all sources of leakage. Leakage sources were identified by Kodak X-OmatV (XV) film placed throughout the enclosure. Radiation inside the enclosure was quantified using Gafchromic film. Outside the enclosure, radiation was measured using a survey meter. Sources of leakage included (1) an unnecessarily broad beam exiting the tube, (2) failure of the secondary collimator to confine the primary beam entirely, (3) scatter from the secondary collimator, (4) lack of beam-stop below the treatment volume, and (5) incomplete shielding of the x-ray tube. The exit window was restricted, and a new collimator was designed to address problems (1–3). A beam-stop and additional tube shielding were installed. These modifications reduced internal scatter by more than 100-fold. Radiation outside the enclosure was reduced to levels compliant with federal regulations, provided the SARRP is operated using tube potentials of 175 kV or less. In addition, these simple and relatively inexpensive modifications eliminate the possibility of exposing a larger animal (such as a rat) to significant doses outside the treatment field.

The American Association of Physicists in Medicine (AAPM) sponsors two summer undergraduate research programs to attract top performing undergraduate students into graduate studies in medical physics: the Summer Undergraduate Fellowship Program (SUFP) and the Minority Undergraduate Summer Experience (MUSE). Undergraduate research experience (URE) is an effective tool to encourage students to pursue graduate degrees. The SUFP and MUSE are the only medical physics URE programs. From 2001 to 2012, 148 fellowships have been awarded and a total of $608,000 has been dispersed to fellows. This paper reports on the history, participation, and status of the programs. A review of surveys of past fellows is presented. Overall, the fellows and mentors are very satisfied with the program. The efficacy of the programs is assessed by four metrics: entry into a medical physics graduate program, board certification, publications, and AAPM involvement. Sixty‐five percent of past fellow respondents decided to pursue a graduate degree in medical physics as a result of their participation in the program. Seventy percent of respondents are currently involved in some educational or professional aspect of medical physics. Suggestions for future enhancements to better track and maintain contact with past fellows, expand funding sources, and potentially combine the programs are presented. PACS number: 01.10.Hx

A reply is provided to the points raised in the comment by Dr Sitek (2016 Phys. Med. Biol. 61 8941) on Polf et al (2015 Phys. Med. Biol. 60 7085).

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.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.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 hydrophone's 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.Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam's 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.

Purpose: The main purpose of this study was to monitor the secondary dose distribution originating from a water phantom during proton therapy of prostate cancer using scintillating fibers.Methods: The Geant4 Monte Carlo toolkit version 9.6.p02 was used to simulate a proton therapy of prostate cancer. Two cases were studied. In the first case, 8 × 8 = 64 equally spaced fibers inside three 4 × 4 × 2.54 cm3 Delrin® blocks were used to monitor the emission of secondary particles in the transverse (left and right) and distal regions relative to the beam direction. In the second case, a scintillating block with a thickness of 2.54 cm and equal vertical and longitudinal dimensions as the water phantom was used. Geometrical cuts were implemented to extract the energy deposited in each fiber and inside the scintillating block.Results: The transverse dose distributions from the detected secondary particles in both cases are symmetric and agree to within -5 MeV per treatment Gy delivered. The distal detectors recorded a negligible amount of energy deposited due to higher attenuation of the secondary particles by the water in that direction.Conclusion: With a good calibration and with the ability to define a good correlation between the radiation flux recorded by the external fibers and the dose delivered to the prostate, such fibers can be used for real time dose verification to the target. The system was also observed to respond to the series of Bragg Peaks used to generate the Spread Out Bragg Peak inside the water phantom. Such Bragg Peaks were detected by the fibers. The energy deposited inside the lateral blocks were also observed to decrease as one goes away from the beam nozzle due to increased attenuation.

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

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.

The latest census indicates the population of Tanzania at 45 million (1), with only 1 radiation therapy center. All treatment of cancer is free of charge for a Tanzanian citizen; however, those who have medical insurance are required to pay through their insurance as cost sharing. Most of the people in Tanzania die with cancer before reaching the Ocean Road Cancer Institute, because the majority are low-income people who cannot afford the expense of medical examinations for early detection. In September of 2013 physicists at the University of Pennsylvania began working with Jumaa bin Dachi, a therapy physicist at the Ocean Road Cancer Institute. We hoped to develop a working quality assurance (QA) program that could be easily implemented from abroad. After entering into this partnership it became readily evident that QAwas not the only area in which we were needed. Instead we found ourselves entering into a bilateral learning partnership over the course of 8 qualitative meetings with Jumaa and established the following needs at the Ocean Road Cancer Institute. Clinical needs were these: local service support; treatment planning for external beam radiation therapy; treatment planning for brachytherapy; clinical markings; quality control of the treatment planning system; portal verification; dosimetry; in vivo dosimetry techniques in radiation therapy; establishment of protocol; radiation protection; and radiobiology. Academic needs included teaching Radiation Therapy Technologists RTT

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.

This paper offers a critical examination of efforts to use Heidegger's thought to illuminate deep ecology. It argues that deep ecology does not entail a non-anthropocentric or ecocentric environmental ethic; rather, it is best understood as offering an ontological critique of the current environmental crisis, from a perspective of deep anthropocentrism.

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

The potential of gold nanoparticles (GNPs) in therapeutic and diagnostic cancer applications is becoming increasingly recognized. These biologically compatible particles can be easily synthesized, tuned to different sizes, and functionalized by conjugation to various biologically useful materials. Efficient and specific delivery to tumor tissue can then be accomplished either by passive accumulation in leaky tumor vessels and tissue, or by directly targeting tumor-specific biomarkers. Tumor-localized GNPs can serve as both adjuvants for enhancing the efficacy of radiation therapy and also as contrast agents for various imaging modalities. In this review, we will discuss recent advancements and future potential in the application of GNP as both a radiosensitizer and an imaging contrast agent. Due to their versatility and biocompatibility, gold nanoparticles may represent a novel theranostic adjuvant for radiation applications in cancer management.