Rui Zhang

The physics of proton therapy

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.

Anonymization of DICOM electronic medical records for radiation therapy

Electronic medical records (EMR) and treatment plans are used in research on patient outcomes and radiation effects. In many situations researchers must remove protected health information (PHI) from EMRs. The literature contains several studies describing the anonymization of generic Digital Imaging and Communication in Medicine (DICOM) files and DICOM image sets but no publications were found that discuss the anonymization of DICOM radiation therapy plans, a key component of an EMR in a cancer clinic. In addition to this we were unable to find a commercial software tool that met the minimum requirements for anonymization and preservation of data integrity for radiation therapy research. The purpose of this study was to develop a prototype software code to meet the requirements for the anonymization of radiation therapy treatment plans and to develop a way to validate that code and demonstrate that it properly anonymized treatment plans and preserved data integrity. We extended an open-source code to process all relevant PHI and to allow for the automatic anonymization of multiple EMRs. The prototype code successfully anonymized multiple treatment plans in less than 1min/patient. We also tested commercial optical character recognition (OCR) algorithms for the detection of burned-in text on the images, but they were unable to reliably recognize text. In addition, we developed and tested an image filtering algorithm that allowed us to isolate and redact alpha-numeric text from a test radiograph. Validation tests verified that PHI was anonymized and data integrity, such as the relationship between DICOM unique identifiers (UID) was preserved.

Inter-Institutional Comparison of Personalized Risk Assessments for Second Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon Craniospinal Irradiation

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient’s body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.

Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

Risk-optimized proton therapy to minimize radiogenic second cancers

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models.

Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.

Visualization of risk of radiogenic second cancer in the organs and tissues of the human body.

BackgroundRadiogenic second cancer is a common late effect in long term cancer survivors. Currently there are few methods or tools available to visually evaluate the spatial distribution of risks of radiogenic late effects in the human body. We developed a risk visualization method and demonstrated it for radiogenic second cancers in tissues and organs of one patient treated with photon volumetric modulated arc therapy and one patient treated with proton craniospinal irradiation.MethodsTreatment plans were generated using radiotherapy treatment planning systems (TPS) and dose information was obtained from TPS. Linear non-threshold risk coefficients for organs at risk of second cancer incidence were taken from the Biological Effects of Ionization Radiation VII report. Alternative risk models including linear exponential model and linear plateau model were also examined. The predicted absolute lifetime risk distributions were visualized together with images of the patient anatomy.ResultsThe risk distributions of second cancer for the two patients were visually presented. The risk distributions varied with tissue, dose, dose-risk model used, and the risk distribution could be similar to or very different from the dose distribution.ConclusionsOur method provides a convenient way to directly visualize and evaluate the risks of radiogenic second cancer in organs and tissues of the human body. In the future, visual assessment of risk distribution could be an influential determinant for treatment plan scoring.

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma patients in LMICs if proton therapy were made available to them. For nine children of ages 2 to 14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37 to 0.75) and 0.64 (95% CI, 0.45 to 0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood medulloblastoma in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

A Treatment Planning Comparison of Volumetric Modulated Arc Therapy and Proton Therapy for a Sample of Breast Cancer Patients Treated with Post-Mastectomy Radiotherapy

Post-mastectomy radiotherapy (PMRT) has been shown to improve disease-free survival and overall survival for locally advanced breast cancer. However, long term survivors may develop life threatening acute and chronic treatment-related toxicities after radiotherapy, like cardiac toxicity and second cancers. The more advanced techniques like volumetric arc therapy (VMAT), and proton therapy have the potential to improve treatment outcome by constraining doses to radiosensitive organs, but evidence from outcome study will not be available until years or decades later. Furthermore, the literature is largely incomplete regarding systematic comparison of potential benefits of advanced technologies for PMRT. The purpose of this study was to compare proton therapy, both passively scattered (PSPT) and intensity modulated (IMPT), to VMAT and develop an evidence-based rationale for selecting a treatment modality for left sided post-mastectomy radiotherapy (PMRT) patients. Eight left-sided PMRT patients previously treated with VMAT were included in this study. Planning target volumes (PTV) included the chest wall and regional lymph nodes. PSPT and IMPT plans were created using a commercial proton treatment planning system. The resulting plans were compared to the corresponding VMAT on the basis of dosimetric and radiobiological endpoints. The uncertainties in risk from proton range, set-up errors, and dose-response models were also evaluated. All modalities produced clinically acceptable treatment plans with nearly 100% tumor control probability. Both proton techniques provided significantly lower normal tissue complication probability values for the heart (p < 0.02) and lung (p < 0.001). Patient-averaged second cancer risk for the contralateral breast and lungs were also significantly lower (p < 0.001) with protons compared to VMAT. The findings of this study were upheld by the uncertainty analysis. All three techniques provided acceptable PMRT treatment plans. Proton therapy showed significant advantages in terms of predicted normal tissue sparing compared to VMAT, taking into account possible uncertainties.

Evaluation of surface and shallow depth dose reductions using a Superflab bolus during conventional and advanced external beam radiotherapy

Abstract The purpose of this study was to evaluate a methodology to reduce scatter and leakage radiations to patients’ surface and shallow depths during conventional and advanced external beam radiotherapy. Superflab boluses of different thicknesses were placed on top of a stack of solid water phantoms, and the bolus effect on surface and shallow depth doses for both open and intensity‐modulated radiotherapy (IMRT) beams was evaluated using thermoluminescent dosimeters and ion chamber measurements. Contralateral breast dose reduction caused by the bolus was evaluated by delivering clinical postmastectomy radiotherapy (PMRT) plans to an anthropomorphic phantom. For the solid water phantom measurements, surface dose reduction caused by the Superflab bolus was achieved only in out‐of‐field area and on the incident side of the beam, and the dose reduction increased with bolus thickness. The dose reduction caused by the bolus was more significant at closer distances from the beam. Most of the dose reductions occurred in the first 2‐cm depth and stopped at 4‐cm depth. For clinical PMRT treatment plans, surface dose reductions using a 1‐cm Superflab bolus were up to 31% and 62% for volumetric‐modulated arc therapy and 4‐field IMRT, respectively, but there was no dose reduction for Tomotherapy. A Superflab bolus can be used to reduce surface and shallow depth doses during external beam radiotherapy when it is placed out of the beam and on the incident side of the beam. Although we only validated this dose reduction strategy for PMRT treatments, it is applicable to any external beam radiotherapy and can potentially reduce patients’ risk of developing radiation‐induced side effects.