Radiotherapy is one of the main methods in the successful treatment of cancer. The tumor is irradiated with photons or charged particles (e.g. protons), and in the case of massive charged particles, the treatment results in less unnecessary dose outside the tumor and therefore less side effects for the patient and a faster recovery. However, the dose planning of hadron therapy is calculated from photon CT measurements, which results in large uncertainties in the planning and therefore in a necessary enlargement of the treatment area. This uncertainty can be reduced by performing the CT scan using protons. The current contribution shows the development of a sampling calorimeter for proton CT measurements and describes the state of the project.
The $^{10}$B isotope has been almost exclusively used in the neutron-capture radiation therapy (NCT) of cancer for decades. We have identified two other nuclides suitable for the radiotherapy, which have ca.10 times larger cross section of absorption for neutrons and emit heavy charged particles. This would provide several key advantages for potential NCT, such as the possibility to use either a lower nuclide concentration in the target tissues, or a lower neutron irradiation flux. By detecting the characteristic $γ$ radiation from the spontaneous decay of the radionuclides, one can image and …
In oncology, treating cancer with a beam of photons is a well established therapeutic technique, developed over 100 years, and today over 50% of cancer patients will undergo traditional X-ray radiotherapy. However, ionizing radiation therapy is not the only option, as the high-energy photons delivering their cell-killing radiation energy into cancerous tumor can lead to significant damage to healthy tissues surrounding the tumor, located throughout the beam's path. Therefore, in nowadays, advances in ionizing radiation therapy are competitive to non-ionizing ones, as for example the laser ligh…
In this paper we present the main ideas and discuss both the feasibility and the conceptual design of a novel hybrid technique and equipment for an experimental cancer therapy based on the simultaneous and/or sequential application of two beams, namely a beam of neutrons and a CW (continuous wave) or intermittent sub-terahertz wave beam produced by a gyrotron for treatment of cancerous tumors. The main simulation tools for the development of the computer aided design (CAD) of the prospective experimental facility for clinical trials and study of such new medical technology are briefly reviewed…
Mechanical force is tightly connected to human health status, and the occurrence of disease can generally be ascribed to certain loss of force balance. However, the role of mechanical approaches in tumor therapy is largely neglected, while the currently available cancer prevention and treatment methods are generally either expensive or just cause too much side effect. In this article, we present a systematic interpretation on a promising strategy which was termed here as Mechanical Therapy for the first time based on the fact that mechanical force closely accompanies the whole life (growth and…
Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe3O4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microsco…
Cold atmospheric plasma (CAP) was shown to affect cells not only directly, but also indirectly by means of plasma pre-treated solution. This study investigated a new application of CAP generated in deionized (DI) water for the cancer therapy. In our experiments, the CAP solution was generated in DI water using helium as carrier gas. We report on the effects of this plasma solution in breast (MDA-MD-231) and gastric (NCI-N87) cancer cells. The results revealed that apoptosis efficiency was dependent on the plasma exposure time and on the levels of reactive oxygen and nitrogen species (ROS and R…
We propose a multi-scale approach to understand the physics related to ion-beam cancer therapy. It allows the calculation of the probability of DNA damage as a result of irradiation of tissues with energetic ions, up to 430 MeV/u. This approach covers different scales, starting from the large scale, defined by the ion stopping, followed by a smaller scale, defined by secondary electrons and radicals, and ending with the shortest scale, defined by interactions of secondaries with the DNA. We present calculations of the probabilities of single and double strand breaks of DNA, suggest a way to fu…
Many therapeutic advantages such as prolonged circulation in the blood, increased tumor drug uptake, enhanced therapeutic efficacy, and markedly reduced toxic side effects are provided by a carbon nanotube based chemotherapeutic formulation. In this system, doxorubicin (DOX) is loaded onto the sidewalls of functionalized single-walled carbon nanotubes by supramolecular pi-pi stacking.
Therapeutic protons acting on O18-substituted thymidine increase cytotoxicity in radio-resistant human cancer cells. We consider here the physics behind the irradiation during proton beam therapy and diagnosis using O18-enriched thymine in DNA, with attention to the effect of the presence of thymine-18 on cancer cell death.
It has been known for about sixty years that proton and heavy ion therapy is a very powerful radiation procedure for treating tumours. It has an innate ability to irradiate tumours with greater doses and spatial selectivity compared with electron and photon therapy and hence is a tissue sparing procedure. For more than twenty years powerful lasers have generated high energy beams of protons and heavy ions and hence it has been frequently speculated that lasers could be used as an alternative to RF accelerators to produce the particle beams necessary for cancer therapy. The present paper review…
Cold atmospheric plasma (CAP) has been emerged as a novel technology for cancer treatment. CAP can directly treat cells and tissue but such direct application is limited to skin or can be invoked as a supplement during open surgery. In this study we report indirect plasma treatment using CAP discharged in DI water using three gases as carriers (argon, helium and nitrogen). Plasma stimulated water was applied to human breast cancer cell line (MDA-MB-231). MTT assay tests showed that using argon plasma had the strongest effect on inducing apoptosis in cultured human breast cancer cells. This res…
A new type of metabolizable and efficient radiosensitizer for cancer radiotherapy is presented in this study by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nano-construct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kid…
In this work, we propose a Machine Learning model that generates an adjustable 3D dose distribution for external beam radiation therapy for head-and-neck cancer treatments. In contrast to existing Machine Learning methods that provide a single model, we create pairs of models for each organ-at-risk, namely lower-extreme and upper-extreme models. These model pairs for an organ-at-risk propose doses that give lower and higher doses to that organ-at-risk, while also encapsulating the dose trade-off to other organs-at-risk. By weighting and combining the model pairs for all organs-at-risk, we are …
We present the theoretical investigation of the single walled carbon nanotubes (SWNTs) as the heating agent of photothermal therapy. In our model, the SWNT is modeled by rigid tube surrounded by cancer cells. In this model, we neglect the angle dependence of temperature and assume that the length of SWNT is much longer than the radius of tube. We calculated the temperature rise of the SWNT and its surrounding cancer cells during the laser heating by solving one-dimensional heat conduction equation in steady state condition. We found that the maximum temperature is located at the interface betw…
This Habilitationsschrift (Habilitation thesis) is focused on my research activities on medical applications of particle physics and was written in 2013 to obtain the Venia Docendi (Habilitation) in experimental physics at the University of Bern. It is based on selected publications, which represented at that time my major scientific contributions as an experimental physicist to the field of particle accelerators and detectors applied to medical diagnostics and therapy. The thesis is structured in two parts. In Part I, Chapter 1 presents an introduction to accelerators and detectors applied to…
We present in vitro and in vivo studies of yttrium-90 (90Y)-labelled human serum albumin magnetic microspheres (HSAMMS) as multifunctional agent for bimodal radionuclide-hyperthermia cancer therapy. The HSAMMS were produced using a modified emulsification-heat stabilization technique and contained 10-nm magnetite nanoparticles coated with citric acid, distributed as inhomogeneous clusters within the albumin microspheres. The average particle size of the complete HSAMMS was 20 (mu)m, and they exhibited superparamagnetic behavior at room temperature. The stability of the 90^Y-labelled HSAMMS was…
The purpose of this study was to use various dosimetrical indices to determine the best IMRT modality technique for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. Intensity modulated radiation therapy plans were designed to include different modalities, including the linac step and shoot, Tomotherapy, RapidArc, and Proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), confo…
A dosimetric and robustness analysis of Proton Arc Therapy (PAT) with Early Energy Layer and Spot Assignment (ELSA) for lung cancer versus conventional Intensity modulated therapy (IMPT)
There are several different modalities, e.g., surgery, chemotherapy, and radiotherapy, that are currently used to treat cancer. It is common practice to use a combination of these modalities to maximize clinical outcomes, which are often measured by a balance between maximizing tumor damage and minimizing normal tissue side effects due to treatment. However, multi-modality treatment policies are mostly empirical in current practice, and are therefore subject to individual clinicians' experiences and intuition. We present a novel formulation of optimal multi-modality cancer management using a f…
University of Texas Southwestern Medical Center（德克萨斯大学西南医学中心）
With the advancement of treatment modalities in radiation therapy for cancer patients, outcomes have improved, but at the cost of increased treatment plan complexity and planning time. The accurate prediction of dose distributions would alleviate this issue by guiding clinical plan optimization to save time and maintain high quality plans. We have modified a convolutional deep network model, U-net (originally designed for segmentation purposes), for predicting dose from patient image contours of the planning target volume (PTV) and organs at risk (OAR). We show that, as an example, we are able…
In the last ten years the use of proton beams in radiation therapy has become a clinical tool for treatment of deep-seated tumours. LIBO is a RF compact and low cost proton linear accelerator (SCL type) for hadrontherapy. It is conceived by TERA Foundation as a 3 GHz Linac Booster, to be mounted downstream of an existing cyclotron in order to boost the energy of the proton beam up to 200 MeV, needed for deep treatment (~25 cm) in the human body. With this solution it is possible to transform a low energy commercial cyclotron, normally used for eye melanoma therapy, isotope production and nucle…
Short single-walled carbon nanotubes (SWNTs) functionalized by PEGylated phospholipids are biologically non-toxic and long-circulating nanomaterials with intrinsic near infrared photoluminescence (NIR PL), characteristic Raman spectra, and strong optical absorbance in the near infrared (NIR). This work demonstrates the first dual application of intravenously injected SWNTs as photoluminescent agents for in vivo tumor imaging in the 1.0-1.4 μm emission region and as NIR absorbers and heaters at 808 nm for photothermal tumor elimination at the lowest injected dose (70 μg of SWNT/mouse, equivalen…
Bi, a high atom number element, has a high photoelectric absorption coefficient, and Se element has anticancer activity. Hence, their compound chalcogenide (Bi2Se3) deserves a thorough investigation for biomedical applications. This study reveals that Bi2Se3 nanoplates (54 nm wide) protected with poly(vinylpyrollidone) (PVP) are biocompatible and have low toxicity even at a high dose of 20 mg/kg in mice. This conclusion was made through the studies on the biodistribution and 90-day long term in vivo clearance of the nanoplates. Liver and spleen were dominant organs for the nanoplates accumulat…
Gold nanoparticles have been conceived as a radiosensitizer in cancer radiation therapy, but one of the important questions for primary drug screening is what size of gold nanoparticles can optimally enhance radiation effects. Herein, we perform in vitro and in vivo radiosensitization studies of 4.8, 12.1, 27.3, and 46.6 nm PEG-coated gold nanoparticles. In vitro results show that all sizes of the PEG-coated gold nanoparticles can cause a significant decrease in cancer cell survival after gamma radiation. 12.1 and 27.3 nm PEG-coated gold nanoparticles have dispersive distributions in the cells…
INTRODUCTION: The Response Evaluation Criteria in Solid Tumors (RECIST) serve as the accepted standard to monitor treatment efficacy in lung cancer. However, the time intervals between consecutive computerized tomography scans might be too long to allow early identification of treatment failure. This study examines the use of breath sampling to monitor responses to anticancer treatments in patients with advanced lung cancer. METHODS: A total of 143 breath samples were collected from 39 patients with advanced lung cancer. The exhaled breath signature, determined by gas chromatography/mass spect…
The use of engineered nanoscale magnetic materials in healthcare and biomedical technologies is rapidly growing. Two examples which have recently attracted significant attention are magnetic particle imaging (MPI) for biological monitoring, and magnetic field hyperthermia (MFH) for cancer therapy. Here for the first time, the capability of a Lissajous scanning MPI device to act as a standalone platform to support the application of MFH cancer treatment is presented. The platform is shown to offer functionalities for nanoparticle localization, focused hyperthermia therapy application, and non-i…
We study the spatial distributions of $β^+$-activity produced by therapeutic beams of $^3$He and $^{12}$C ions in various tissue-like materials. The calculations were performed within a Monte Carlo model for Heavy-Ion Therapy (MCHIT) based on the GEANT4 toolkit. The contributions from $^{10,11}$C, $^{13}$N, $^{14,15}$O, $^{17,18}$F and $^{30}$P positron-emitting nuclei were calculated and compared with experimental data obtained during and after irradiation. Positron emitting nuclei are created by $^{12}$C beam in fragmentation reactions of projectile and target nuclei. This leads to a $β^+$-a…
We propose a series of simulations about the potential use of Boron isotopes to trigger neutron-free (aneutronic) nuclear reactions in cancer cells through the interaction with an incoming energetic proton beam, thus resulting in the emission of characteristic prompt gamma radiation (429 keV, 718 keV and 1435 keV). Furthermore assuming that the Boron isotopes are absorbed in cancer cells, the three alpha-particles produced in each p-11B aneutronic nuclear fusion reactions can potentially result in the enhancement of the biological dose absorbed in the tumor region since these multi-MeV alpha-p…
Radiation therapy with carbon ions is a novel technique of cancer radiotherapy, applicable in particular to treating radioresistant tumours at difficult localisations. Therapy planning, where the medical physicist, following the medical prescription, finds the optimum distribution of cancer cells to be inactivated by their irradiation over the tumour volume, is a basic procedure of cancer radiotherapy. The main difficulty encountered in therapy planning for ion radiotherapy is to correctly account for the enhanced radiobiological effectiveness of ions in the Spread Out Bragg Peak (SOBP) region…
Theranostics, the combination of diagnosis and therapy, has long held promise as a means to achieving personalised precision cancer treatments. However, despite its potential, theranostics has yet to realise significant clinical translation, largely due the complexity and overriding toxicity concerns of existing theranostic nanoparticle strategies. Here, we present an alternative nanoparticle-free theranostic approach based on simultaneous Raman spectroscopy and photodynamic therapy (PDT) in an integrated clinical platform for cancer theranostics. We detail the compatibility of Raman spectrosc…
In this paper, we discuss biological effects of electromagnetic (EM) fields in the context of cancer biology. In particular, we review the nanomechanical properties of microtubules (MTs), the latter being one of the most successful targets for cancer therapy. We propose an investigation on the coupling of electromagnetic radiation to mechanical vibrations of MTs as an important basis for biological and medical applications. In our opinion optomechanical methods can accurately monitor and control the mechanical properties of isolated MTs in a liquid environment. Consequently, studying nanomecha…
I propose to use high brightness electron beam with 1 to 100 MeV energy as tool to combat tumor or cancerous tissues in deep part of body. The method is to directly deliver the electron beam to the tumor site via a small tube that connected to a high brightness electron beam accelerator that is commonly available around the world. Here I gave a basic scheme on the principle, I believe other issues people raises will be solved easily for those who are interested in solving the problems.
Cancer is a primary cause of morbidity and mortality worldwide. The radiotherapy plays a more and more important role in cancer treatment. In the radiotherapy, the dose distribution maps in patient need to be calculated and evaluated for the purpose of killing tumor and protecting healthy tissue. Monte Carlo (MC) radiation transport calculation is able to account for all aspects of radiological physics within 3D heterogeneous media such as the human body and generate the dose distribution maps accurately. However, an MC calculation for doses in radiotherapy usually takes a great mass of time t…
This study evaluates dynamic conformal arc (DCA) therapy as an alternative to volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of lung cancer. The rationale for DCA is lower geometric complexity and hence reduced risk for interplay errors induced by respiratory motion. Forward planned DCA and inverse planned DCA based on segment-weight optimization were compared to VMAT for single arc treatments of three lung patients. Analysis of dose-volume histograms and clinical goal fulfillment revealed that DCA can generate satisfactory and near equivalent dosimetric…
Patient-Specific Deep Reinforcement Learning for Automatic Replanning in Head-and-Neck Cancer Proton Therapy
Department of Radiation and Cellular Oncology University of Chicago（辐射与细胞肿瘤学系，芝加哥大学）；Division of Environmental and Occupational Health Sciences University of Illinois at Chicago（环境与职业卫生科学系，伊利诺伊大学芝加哥分校）；Department of Radiation Oncology and Winship Cancer Institute Emory University（放射肿瘤学系和Winship癌症研究所，埃默里大学）
Transmission intensity of a thin tissue sample produce intensity distribution that is proportional to the refractive index pattern in the thin slice, in turn reflects mass density pattern, and using the intensity pattern, fractal dimension can be calculated. In this paper, we report fractal dimension analyses of MUC13 stained pancreatic cancer tissues. Pancreatic cancer is deadliest due to its physical orientation, and no prominent chemical change till the late stages of cancer. The presence of pancreatic cancer can be detected using MUC13, however this fails to explain about the stages of can…
Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods: Recently, a fast and accurate Graphics Processor Unit (GPU)-based MC simulation of proton transport was developed and used as the dose calculation engine in a GPU-accelerated IMPT optimizer. Besides dose, the dose-averaged linear energy transfer (LETd) can be simultaneously scored, which makes biological dose (BD) optimization possible. To convert from LETd to BD, a linear relation was assumed. Using this novel op…
Protontherapy is hadrontherapy fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) $^{12}$C ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper $^{12}$C-ion clinical amenability. Thus, e…
UT Southwestern Medical Center（德克萨斯大学西南医学中心）；University of North Texas（北德克萨斯大学）；UCLouvain（鲁汶大学）；Erasmus University Medical Center（伊拉斯姆斯大学医学中心）
This work aims to study the generalizability of a pre-developed deep learning (DL) dose prediction model for volumetric modulated arc therapy (VMAT) for prostate cancer and to adapt the model to three different internal treatment planning styles and one external institution planning style. We built the source model with planning data from 108 patients previously treated with VMAT for prostate cancer. For the transfer learning, we selected patient cases planned with three different styles from the same institution and one style from a different institution to adapt the source model to four targ…
Laser illumination of tissue results in a characteristic fluorescence emission spectrum whose features depend on the type of tissue, viz., healthy, adenoma or malignant. Hence measurement of the fluorescence is potentially a rapid and reliable diagnostic method. We have applied the technique to thyroid tissues and found that judicious normalization of the fluorescence spectrum reveals a close correlation between spectral shape and tissue type. Hence the pathological state of the tissue can be unambiguously identified from the laser-induced fluorescence spectrum. The method is rapid and portabl…
We present a novel application of Tensor Network methods in cancer treatment as a potential tool to solve the dose optimization problem in radiotherapy. In particular, the Intensity-Modulated Radiation Therapy (IMRT) technique - that allows treating irregular and inhomogeneous tumors while reducing the radiation toxicity on healthy organs - is based on the optimization of the radiation beamlets intensities. The optimization aims to maximize the delivery of the therapy dose to cancer while avoiding the organs at risk to prevent their damage by the radiation. Here, we map the dose optimization p…
Cancer therapy using protons and heavier ions such as carbon has demonstrated advantages over other radiotherapy treatments. To bring about the next generation of clinical facilities, the requirements are likely to reduce the footprint, obtain beam intensities above 1E10 particles per spill, and achieve faster extraction for more rapid, flexible treatment. This review follows the technical development of ion therapy, discussing how machine parameters have evolved, as well as trends emerging in technologies for novel treatments such as FLASH. To conclude, the future prospects of ion therapy acc…
We propose a new model of cancer growth based on nonextensive entropy. The evolution equation depends on the nonextensive parameter q. The exponential, the logistic, and the Gompertz growth laws are particular cases of the generalized model. Experimental data of different tumors have been shown to correspond to all these tumor-growth laws. Recently reported studies suggest the existence of tumors that follow a power law behavior. Our model is able to fit also these data for q<1. We show that for q<1, the commonly used constant-intensity therapy is unable to reduce the tumor size to zero. As is…
University of Toronto（多伦多大学）；Princess Margaret Cancer Centre（玛格丽特公主癌症中心）；York University（约克大学）
Knowledge-based planning (KBP) is an automated approach to radiation therapy treatment planning that involves predicting desirable treatment plans before they are then corrected to deliverable ones. We propose a generative adversarial network (GAN) approach for predicting desirable 3D dose distributions that eschews the previous paradigms of site-specific feature engineering and predicting low-dimensional representations of the plan. Experiments on a dataset of oropharyngeal cancer patients show that our approach significantly outperforms previous methods on several clinical satisfaction crite…
