Faculty Summaries
C-M Charlie Ma, PhD
C-M Charlie Ma, PhD
Professor
  • Vice Chairman, Department of Radiation Oncology
  • Director, Radiation Physics
Charlie.ma@fccc.edu
Office Phone: 215-728-2996
Fax: 215-728-4789
Office: P2028
  • Radiation Physics

    The Radiation Physics section consists of medical physicists, medical physics residents, research fellows and students, accelerator engineers, dosimetrists, simulation and therapy technologists and other technical and supporting staff, who are responsible for accurate planning and delivery of radiation dose for radiation oncology. The mission of the radiation physics section is to provide the best possible technical support for clinical radiation therapy and to advance the efficacy of cancer treatment through the integration of new technical innovations with clinical research. Our current research includes image-guided radiation therapy (IGRT) employing intensity modulated radiation therapy (IMRT) and energy and intensity modulated electron therapy (MERT), stereotactic radiosurgery and radiotherapy (SRS/SRT), advanced imaging techniques for structure delineation, target definition and localization, deformation registration, image recognition, organ motion compensation, MRI based treatment planning, MR-guided focus ultrasound (MRgFUS) enhancement of drug delivery for gene therapy and chemotherapy, MR-guided high-intensity focused ultrasound (HIFU) surgery, Monte Carlo dose calculation, laser accelerated proton and light ion beams, advanced image-based treatment assessment, and analyses of biological effects of radiation.

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  • Advanced radiotherapy planning techniques for dose escalation and hypofractional trials

    Since 2000, we have treated 5000 patients with intensity-modulated radiotherapy (IMRT) at Fox Chase Cancer Center (FCCC). Roughly 10% of these patients were treated for disease in the head and neck (H&N) region. Radiotherapy patients treated for H&N cancer often lose weight and have shrinkage of their tumors causing drastic anatomical changes. This can result in changes in the dose distribution with respect to planning target volume (PTV) coverage and critical structures or planning volumes at risk (PRV). Monitoring these changes is difficult and presents quality assurance (QA) problems for IMRT treatments. By using Electronic portal imaging device (EPID) transmission dosimetry, we have developed a method to monitor H&N thickness changes and adjust the dose distribution in response to indicated changes. Tissue equivalent wax was applied to the neck region of an anthropomorphic phantom in 3-1cm layers. Contours depicting tumor and critical structures were delineated. A dose of 70Gy was virtually delivered to the phantom with layers of wax removed simulating weight loss. PTV coverage, hot spot, and PRV doses were recorded. The phantom was then consecutively imaged removing 1cm layers of wax. Using the amorphous silicon EPID on a Varian 21EX linear accelerator and slabs of solid water, a characteristic response curve was generated. By analyzing the resultant gray-scale of each phantom image using the aforementioned curve and in-house developed software, we were able to predict changes in the lateral dimension of the phantom to within 2–4mm. By comparing the results with a library of phantom plans, this method of monitoring may be used to determine if re-planning is necessary and is limited only by the frequency of image acquisition and PTV and PRV specific dose criteria. The implementation of this technique in conjunction with image-guided radiotherapy (IGRT) is helping us investigate methods to alter radiation delivery in real-time as dictated by anatomical changes (adaptive radiotherapy). Another use of this technique may be the application to IMRT treatment of the breast. Volume and topographical changes in breast tissue may result in unanticipated dose distributions that may affect cosmesis. By analyzing the pathlength changes along the tangential field ray lines acquired during weekly port filming, it may be possible to morph the external skin contour generated from the initial planning CT study to a data set representing the patient’s physical changes. This would allow for re-planning or adaptive planning without the need to acquire a new CT data set delivering additional dose to the contra-lateral breast.

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  • Advanced extracranial stereotactic radiotherapy techniques and intensity modulated Radiosurgery

    Since we implemented stereotactic body radiotherapy (SBRT) clinically in our institution, we have been conducting research on some of the clinical issues related to the improvement of the technique effectiveness and efficacy for the SBRT. One of the issues is the target definition for tumors in the thorax regions. The fact that tumors have most intra-fractional motion due to respiration in this region creates great challenges in treatment planning and treatment delivery of lung cancer with SBRT. Respiratory tumor motion during simulation CT acquisition can introduce severe motion artifacts, resulting in inaccurate assessment of organ shape and locations. To eliminate any artifacts due to respiratory motion, we previously took a multi-phase CT scanning approach in which 3 sets of CT scans are taken at different respiratory phases (including maximum inhalation and exhalation, respectively) during a simulation. The 3 multiphase CT scan approach makes an underlying assumption that images taken during breath-holding at the end-tidal inspiration and end-tidal expiration will best define the target extreme motion positions, thus accounting for breathing motion at all respiratory phases. We have been working to verify this assumption using different approaches. One of the approaches is to directly compare the motion measured from the 3 multiphase CT scans with those obtained from MRI cine study by measuring the variation of the tumor center along the three major directions. This study was performed for 10 patients and the motions determined by 3 CT scan and MRI cine measurements are very comparable. Another approach is performed indirectly through a comparison of dosimetric coverage between the target in the treatment position (through CT scan prior to a treatment) and the plan for the assumed target by accounting for patient-specific motion. The underlying assumption for this approach is that if a moving target at any instant (captured by the prior-treatment CT images) position receives the same coverage as the plan target, then the initial target accounts for the tumor motion. We have confirmed that the coverage of the target in the treatment position (after corrections for any setup error) is indeed the same as that of the plan target. Another issue regarding the SBRT concerns the selection of optimal beam margins for hypofractionated lung cancer treatment. As the dose is increased, the toxicity to normal lung tissue and adjacent structures such as the esophagus, spinal cord, and thoracic wall may also increase substantially. For this reason, many investigators have adopted the principle used for intracranial SRS, i.e., applying a focal dose distribution with a sharp dose gradient for SRT lung treatment. Currently there is no general standard or consensus to follow, although it is usual to mimic the intracranial SRS using very small beam margins (less than 2 millimeters). The purpose is to maximize the dose fall off in order to decrease the dose to the surrounding normal tissues. However, as lung targets usually lie in a region of significant tissue inhomogeneity, even a conventional block margin (5–6 mm) that accounts for beam penumbra in water is no longer enough to ensure target coverage. Furthermore, hypofractionated SRT treatment planning usually deals with small target volumes for which the field sizes may not ensure lateral electronic equilibrium. The combination of these factors may have a unique impact on beam port design and margin selection—a research topic that needs our investigation. In order to provide a clinical guideline for beam margin selections in conformal treatment planning of hypofractionated radiotherapy of lung cancer, we have performed Monte Carlo dose calculations. We studied the dosimetric quality of previous clinical SBRT treatment plans due to different beam margins used, along with different lung densities for different planning target volume (PTV) sizes under a patient geometry. Based on accurate calculations for ninety SBRT plans, we were able to establish relationships between the maximum target dose or lung toxicity (in terms of lung V20) as a function of beam margin, as well as lung density and PTV size. We found that the optimal beam margin is about 4 mm for all cases studied, after considering target coverage with lung toxicity.

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  • MR-guided high-intensity focused ultrasound for radiotherapy

    An MR guided (1.5 T GE medical systems) high-intensity focused ultrasound (HIFU) system (InSightec ExAblate 2000) has been installed in our department in August 2006 (see the Figure: High-intensity focused ultrasound). HIFU has long been known to offer the potential of very precise “trackless ablation” but has only recently, with the current high quality methods of medical imaging, become a practical possibility in clinical treatment. High quality image techniques can provide precise visualization and localization of the tissue damage. The potential clinical applications for cancer treatment include brain cancer, breast cancer, liver cancer, prostate cancer and bone metastases. With our current system the ultrasound can also be emitted in short, high energy pulses resulting in focused regional shock waves that may alter vascular permeability without permanently damaging the tissue. The increased vascular permeability will concentrate macromolecular pharmaceutical agents to the treatment target and MR imaging can be used to place the ultrasound beam in the target area and monitor the effect of the treatment. Studies have been carried to investigate the effect of the treatment in combination with radiation. The significance of this study is to demonstrate that the increase of anti-cancer drugs uptake in prostate tumors, in combination with radiation, will have the potential to greatly improve local control in prostate cancer patients.

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  • MRI-based treatment planning and MRS guided radiotherapy

    MRI-based treatment planning for radiation therapy has been implemented clinically at FCCC. Our previous studies were focused on prostate IMRT, where the treatment geometry can be properly simulated using homogeneous geometry for dose calculation and treatment setup. MRI-based planning can be applied to other treatment sites provided that the treatment geometry does not include significant heterogeneities such as large air cavities or bony structures. A good candidate for such treatment is the brain. CT and MR fusion errors can be a few millimeters for brain patients due to the geometric complexity of the bony structures. Treatment planning based on MRI alone can remove this fusion error. We have investigated the dosimetric accuracy of MR-based treatment planning for brain tumor. Our previous MR unit, the 0.23 Tesla MR scanner (Philips Medical Systems, Cleveland, OH) has been replaced by the 1.5 Tesla scanner (GE Medical Systems) since August 2006. The new MR scanner can offer us the better quality of MR imaging for MR simulations. Different MR imaging protocols have been developed for different sites such as for brain, liver, stomach, prostate, etc. With the new MR imaging systems MR spectroscopy (MRS) has also been clinically implemented since October 2006. Prostate and brain cancer patients can be scanned routinely for the spectroscopy. The MRS can help oncologist to determine the treatment target more accurately resulting the better radiation treatment outcomes.

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  • Development of advanced mixed beam therapy using IMRT and MERT
    High-intensity focused ultrasound (HIFU)
    High-intensity focused ultrasound (HIFU)

    We have investigated software and hardware tools for advanced mixed beam radiation therapy (MBRT) treatment of breast and head and neck cancer using energy- and intensity-modulated photon and electron beams. The new technique is being implemented clinically for dose escalation and hypofractionation studies. The new MBRT system consists of multileaf collimators (MLC) for both photon and electron beam modulation and the associated software for dose calculation, treatment optimization, and beam delivery to ensure superior target coverage and normal tissue sparing. We have investigated energy- and intensity modulation using photon multileaf collimators (pMLC) on both Varian and Siemens accelerators. We studied the beam properties collimated by these pMLCs using Monte Carlo simulations and evaluated MBRT beam delivery accuracy and efficiency with phantom measurements. Accurate and efficient dose calculation tools for Monte Carlo based treatment planning and effective treatment optimization and leaf sequencing algorithms for efficient and accurate beam delivery for advanced MBRT were developed. This technique is being implemented clinically for breast and head and neck treatment through pilot studies and clinical trials that are specially designed for dose escalation and hypofractionation. Partial breast treatment is also investigated using advanced MBRT as it is being developed. Results based on 76 patients showed that grade II skin complications were significantly reduced in a hypofractionated breast trial. The whole breast received 20 fractions of 2.25 Gy and the tumor bed received an additional 0.55 Gy/day concurrent electron boost. The elimination of 10% hot spots in the whole breast volume ensures that the whole breast dose is under 2.5 Gy, (beyond which significant skin complications usually occur). New treatment designs are studied for head and neck cancers. We are also working on electron-specific multileaf collimators (eMLC). Figure Electron-specific multileaf collimator, below, shows an eMLC under investigation for MBRT. Software and hardware tools are being developed to achieve improved target dose conformity and uniformity, adequate skin coverage/avoidance and significant reduction in the dose to the adjacent normal organs and critical structures.

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  • Image-guided target localization and gating using 4D CT techniques
    Electron-specific multileaf collimator
    Electron-specific multileaf collimator

    4D CT is a new imaging tool in radiotherapy to enhance the ability to conform the dose to the treatment target that is affected by respiratory induced motion. The respiratory-induced motion of the tumor and normal tissues in thoracic and abdominal regions can be visualized and simulated in a 3D space. This information is useful for both the planning and delivery of patient’s treatment. Because the motion artifacts of patient anatomy is much reduced compared to that seen in a regular free-breathing CT scan, the delineation of the target volume and adjacent normal tissues for treatment planning will be more accurate. The planning target volume for radiation can be constructed based on the trajectory of the tumor motion with less normal tissues involved. The dose conformity of the treatment plan is enhanced with a safe reduction of the geometric margin that would be required without an exact knowledge of tumor motion and an artifact free imaging of patient anatomy.

    A variety of strategies of treatment delivery are available to deal with our ability to simulate the patient respiratory motion. One technique is the gated treatment with the radiation beam synchronized to certain phases of the respiratory cycle when the tumor is in a relatively stable position. 4D CT has been implemented for clinical use at Fox Chase since April of 2006. Gated treatment was provided to a subgroup of these patients with the magnitude of tumor motion greater than 5 mm. In order to evaluate the benefits of 4D CT we studied the target volumes for lung patients treated with stereotactic radiosurgery. The purpose of this study is to assess the difference between the target volume delineated using breath holding CT scans at inspiration and expiration, a technique commonly used when 4D CT was not available, and the volume based on 4D CT. In three of the four patients analyzed at this time, the 4D CT volume is more than 42% smaller compared to the composite volume of two breath-holding CT scans and the free breathing scan. The significant difference is due to the extreme tumor motion shown by the breath holding CT scans, which may not be an accurate simulation of the tumor motion when the patient breaths normally at the treatment, and due to inadequate information about the actual trajectory of the tumor motion. 4D CT can also be used to evaluate the change of dose distribution due to respiratory motion. We have utilized 4D CT scans to measure the breast motion and related dose effect for women undergoing IMRT for breast cancer. 20 women, 10 with left breast cancer and 10 with right breast cancer, who were being simulated for breast radiotherapy underwent a free breathing 4D CT scan in our department. An average intensity projection scan was constructed from the 4D dataset. The CT dataset was analyzed in detail in order to identify the two phases of the respiratory cycle, which represented the extremes of respiration. Contouring was then performed on the average scan as well as on the two extreme phases identified. Among the 20 datasets analyzed, the amount of breast motion was minimal (0–4 mm). The greatest magnitude of motion was seen in the axial and sagittal directions, while the least was in the coronal plane. In order to assess the coverage of the breast and the doses to the normal structures throughout the respiratory cycle, the IMRT plan generated from the average intensity projection scan (which was used to treat the patient) was superimposed onto the two phases of the respiratory cycle representing the extremes of motion. Minimal dosimetric differences were seen among the extremes of respiration. The conclusion of this study is that 4D CT simulation is unnecessary for breast radiotherapy treatment planning, as the motion of the breast is minimal during normal quiet breathing. This is somewhat contradictory to similar studied conducted at other institutions. We attribute the outcome to present IMRT methods and rigorous acceptance criteria in target dose uniformity and normal structure sparing being implemented at our institution.

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  • 4D Image-guided target localization for prostate therapy using the Calypso technique

    Two Calypso systems have been installed and hundreds of prostate patients have been treated with 4D target localization using the Calypso system (Seattle, WA). Our research have focused on the threshold values for real-time intervention for the 4D image-guided treatment process and the effect of Beacon migration and rotation on the target localization accuracy. In a recent study, we reviewed the inter-transponder distances reported by the Calypso system at the first and last treatment fraction and compared with those obtained from our analysis based on cone-beam CT scans for 105 patients. The results showed that the average changes of the inter-Beacon distance for the 3 implanted Beacons were -0.84, -0.88, -0.23mm at the fist treatment and -1.72, -2.0, -1.27mm at the last treatment. The average ratios of distance relative to those in the simulation CT are 0.94, 0.92 and 0.96 for the last treatments. The inter-Beacon distance increased by 7mm or decreased by 16mm for some cases while most changes are from -5mm to 3mm. The distance changed continuously during the treatment for most patients. The inter-transponder distance varied between -4mm and 2mm from the first to the last treatment for most patients and the maximum changes were between -6.6mm and 7.3mm. These findings are confirmed by CBCT and the potential causes were found to be the transponder migration, prostate shrinkage and deformation due to rectal/bladder fillings. The effect on the centroid position and thus the isocenter accuracy is within 2.5mm for most patients. It was concluded that the inter-transponder distance changed significantly for some patients and its effect should be considered clinically for transponder-based target localization.

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  • Monte Carlo treatment planning for the Cyberknife system
    Diagram, Cyberknife lung treatment
    Diagram, Cyberknife lung treatment

    A Monte Carlo dose calculation engine and a beam commissioning tool have been developed for the Cyberknife system (Accuray, Sunnyvale, CA). Monte Carlo simulations of the Cyberknife system have been performed using the BEAMnrc Monte Carlo code system to obtain the phase space that corresponds to the measured depth dose curves (PDD) of a clinical unit. Phantom dose calculations were carried out using the MCSIM Monte Carlo system with a standard set of transport parameters and energy cutoffs. Phase space files for different cones were generated. Good agreement was achieved in PDDs and beam profiles for all the cones between Monte Carlo simulations and measurements (within 2% dose difference in low dose gradient regions or within 2 mm isodose line shift in high dose gradient regions). Patient dose calculations were performed showing differences of up to 15% of the prescription dose in some plans between Monte Carlo simulations and the results from the treatment planning system (see Figure Diagram, Cyberknife lung treatment, above), indicating the need for accurate patient dose calculation using the Monte Carlo method. The Monte Carlo method is a random sampling technique that simulates radiation interactions and particle transport. In order to speed up the Monte Carlo dose calculation, a superposition Monte Carlo code was developed with several variance reduction techniques for this project. Dose calculations were performed in phantom and patient geometry and compared with full Monte Carlo simulations. Excellent agreement was achieved (within 0.5%) and the calculation time was reduced by up to 62 times. To facilitate Monte Carlo treatment planning dose calculation for the Cyberknife system, an automatic beam commissioning procedure has been developed and benchmarked to generate a source model based on the measurement data. The source model consists of a single photon source located at target level of the Cyberknife treatment head. The photon source is assumed to be cylindrically symmetrical with a source distribution, which can be determined based on the measured in-air cone output factors. The energy spectrum of the photon source is determined from the measured central axis PDD in water at 80 cm SSD for the 60 mm cone. The fluence distribution of the photon source is obtained from the measured profile at depth with cone (secondary collimator) totally removed. With the energy spectrum, the fluence and source distributions known, one can reconstruct the beam phase space one particle at a time with a beam sampling routine, and use the reconstructed phase space as source input for forward Monte Carlo dose calculations in patient geometry.

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  • Development of a laser-accelerated proton/ion radiotherapy system
    Laser proton accelerator
    Laser proton accelerator

    Both theoretical and experimental results have shown that proton (light ion) acceleration can be achieved using laser-induced plasmas. For the last few years we have been studying a new proton therapy system for radiation oncology, which employs laser-accelerated protons. We have acquired a 100 TW laser system for the experimental studies. Depending on the pulse duration and focal spot size, we can achieve light intensities between 0.1–4.0 1020 W/cm2. Initial experiments with low-power (3–6 TW) laser pulses have generated 500 keV protons as measured on the CR-39 film. Because of the extremely small acceleration distance and the particle selection and beam collimating device we expect that the new system will be compact, cost-effective and capable of delivering energy- and intensity-modulated proton therapy (EIMPT). We have performed particle-in-cell (PIC) simulations to investigate optimal target configurations for proton/ion acceleration. Monte Carlo simulations were carried out on the beam characteristics and the feasibility of using such beams for cancer treatment. Since laser-accelerated protons have broad energy and angular distributions, which are not suitable for radiotherapy applications directly, we have designed a compact particle selection and beam collimating system for EIMPT beam delivery. We designed a new gantry to make the whole system compact to retrofit existing linac vaults. We compared Monte Carlo calculated dose distributions for prostate treatments using X-ray IMRT and laser-proton EIMPT. The results show that EIMPT using laser protons produces superior target coverage and much reduced critical structure dose and integral dose compared to x-ray IMRT.

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  • Parametric studies of proton acceleration using high power, ultra-short laser pulses
    Experimental acceleration for proton acceleration
    Experimental acceleration for proton acceleration

    Recent advances in laser amplification techniques have created a possibility of constructing a compact laser system that can be used to accelerate protons and other ions to extremely high energies. Using ultra-short laser pulses with peak intensity reaching 1021 W/cm2 level directed onto the thin high-density foil, we can accelerate ions to energies suitable for radiation therapy applications. Our recent particle in cell simulation results reveal a new proton acceleration regime that could potentially increase the maximum proton energy by up to 50% compared to conventional target designs used currently in experiments. The method utilizes the proper synchronization of the arrival time of protons with the temporal evolution of the electric field of the target (Coulomb mirror effect).

    Figure Experimental acceloratin for proton acceleration, above, shows the experimental setup that can be used to test the 

    Coulomb mirror effect
    Coulomb mirror effect

    proposedtheoretical model. In stage I, a fraction of the laser power (intensity αI0) interacts with a double-layer target to produce a quasi-monoenergetic proton bunch of energy T1 that is further accelerated to energy T2 in a Coulomb mirror setup (stage II)pumped by the remaining laser power (1-α) I0. For a fixed distance between the two targets, adjustment of the timing of the second laser pulse is necessary to obtain optimum acceleration conditions in stage II. According to our theoretical model, for a given value of the splitting parameter a (kinetic energy T1) and fixed distance between the two targets, one can find an optimum delay of the second laser pulse that ensures correct arrival time of the proton bunch generated in stage I. In the Figure Coulomb mirror effect, the final kinetic energy of the accelerated protons versus the splitting parameter a. As can be seen one should expect between 30 to 50% increased kinetic energy in the accelerated bunch of protons for the same level of intensity of the laser pulse.

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  • Radiobiological studies and radiation protection

    Our radiobiological studies have focused on the investigation of tumor control probability (TCP) and normal tissue complication probability (NTCP) for the design of new dose schemes and treatment techniques. We have studied the variation of some biological parameters for a given patient population to define the dose range that will ensure adequate local control for conventional treatment, dose escalation and hypo-fractionated treatment. To investigate the potential of laser-accelerated proton beams for radiation therapy, we performed treatment plan comparisons between IMRT and IMPT with a consideration of variable relative biological effectiveness (RBE) for protons near the end of their range. The RBE of light ions (e.g., carbon ions) can be significantly different from that of photons and electrons. This effect is being accounted for in performing dose calculations for treatment planning and comparing different dose schemes. Another study is being carried out on the effect of the short exposure time for laser accelerated particle beams, typically at 10s to 100s femtosecond. This may alter the RBE of laser-accelerated protons compared to protons from conventional accelerators. We also studied the treatment head design for laser accelerated proton beams. Different target, collimator and shielding materials have been simulated using the Monte Carlo method to provide data for the therapy gantry and room design to meet the state shielding requirement for our laser-proton radiotherapy facility.

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