The two fundamental and evolving themes of radiation therapy have been the increase in knowledge regarding the location and behavior of tumor cells in the patient and the increasingly selective delivery of radiation to those tumor cells, therby improving the therapeutic ratio of the treatment.
The physical properties of protons and heavier charged particles, whereby dose is largely deposited in the narrow Bragg peak at a fixed depth in tissue without dose beyond this peak, provide clinicians with a tool to sharply conform the radiation dose around the tumor, thereby permitting selective delivery of external radiation to the tumor. It is anticipated that ongoing improvements in tumor imaging with molecular imaging will further improve the clinician's ability to understand where viable tumor cells are and where radiation dose needs to be deposited. Charged particles are ideal tools for taking full advantage of these improvements in tumor imaging and are expected to permit dose painting areas to tumor where hypoxia, accelerated tumor proliferation, or other tumor profiles that might be associated with radiation resistance are imaged.
The precision of dose deposition with charged particles means that radiation doses can be delivered to the tumor with less irradiation to the surrounding normal tissue and permits selective dose escalation to the tumor. Because higher radiation doses to the tumor increase the likelihood of sterilizing the tumor cells and because irradiation of less normal tissue and/or delivery of lower dose to the same or smaller volume of normal tissue result in fewer treatment related complications, protons and charged particles provide the opportunity to improve the therapeutic ratio by increasing the tumor cure probability while simultaneously reducing the risk of normal tissue complications. It is anticipated the use of intensity-modulated proton therapy (IMPT) will further increase this therapeutic ratio.
Interest in the clinical use of protons beams was stimulated by R. Wilson, who in 1946 noted the clinical potential of the physical characteristics of protons. The initial clinical tests were by researchers at facilities originally designed and installed for basic high-energy physics research. Treatments were, as a consequence, much more cumbersome and limited compared to those which could be given in a hospital clinic. The proton beams were limited to a fixed horizontal position, which meant that the patient had to be moved to align the tumor on the trajectory of the beam. This contrasted sharply with the isocentric capabilities of the linear accelerator, which rotates around a point in space and can effectively target any site in the body from an arbitrary direction. For linear accelerator x-ray treatments, the patient is generally in a comfortable supine or prone position on a moveable table, while the machine can be moved to orient the x-ray beam with respect to the target. In proton therapy, patients often had to be immobilized in unusual and difficult-to-reproduce decubitus or angled body positions that were less comfortable and at times limited the choice of beam trajectories. In addition, for many of the proton machines, the beam energy, which defines the depth of the Bragg peak, was limited. Few had sufficient energy to treat all sites in the body. Because of these limitations and the interests of the involved practitioner, the clinical sites that initially received the most interest were uveal melanomas in the eye and base of skull sarcomas. The major emphasis for proton therapy clinical research initially was dose escalation for tumors for which local control with conventional radiotherapy was poor, initially including base of skull tumors, locally advanced prostate cancer, hepatocellular carcinoma, and medically inoperable non-small cell lung cancer.
The development of hospital-based cyclotrons with higher energy beams capable of reaching deep-seated tumors (up to ~34 cm with a 235-MeV beam), field sizes comparable to linear accelerators, and rotational gantries puts proton radiation therapy delivery on par with the photon radiation therapy clinic. Commercial vendors are now able to build these facilities on-time and on-budget and multiple institutions around the world are committing resources to acquiring these facilities. Hence, proton radiotherapy will be available to many more patients and can now be extended to of the full complement of clinical sites. Increasingly, there is interest in protocols aimed at morbidity reduction in those tumor sites in which tumor control with photons is good. Many pediatric tumors fall into this category. It is to be emphasized that dose escalation and morbidity reduction are not mutually exclusive when using protons and that the opportunity for both may be present in any given patient.
Much of the clinical experience to date has been with proton beams and much of this book focuses on the use of the proton beam in the clinic. One property of charged particle dose deposition, the linear energy transfer (LET) or rate of energy loss per unit distance, relates to the biological impact of a particular radiation type in tissue. The radiobiology of protons is similar to that of photons. Photons, protons, and helium ions are therefore considered low-LET, and biologically equivalent, radiation. The adoption of protons by clinicians can therefore build directly upon, and evolve from, prior experience with photons.
Heavier charged particles (neon, carbon) and fast neutrons are considered high-LET radiation. There is an initial increase in the relative biological effectiveness (RBE) with an increase in LET. High-LET radiation response in tissue is less influenced by oxygenation and less sensitive to variations in the cell cycle and DNA repair. The combination of the higher RBE with the highly conformal dose distributions that can be achieved with these particles might be advantageous for treatment of some tumors in the clinic. It should be noted that the disappointing experience with neutrons (with an RBE of 3) in many clinical sites was related to the suboptimal dose distribution that could be achieved with neutrons in the clinic. As a consequence, the observed higher normal tissue complication rates related to the higher RBE effect on normal tissue. It is hoped that these normal tissue complications can be avoided with heavy charged particles because of the inherent ability to precisely control the dose deposition in the patient. The major heavy-particle experience to date has been with carbon beams and this experience will be discussed.
Besides LET, the critical clinical variable is the fractionation schema applied to the treat a particular disease. To wit, the RBE is a function of LET and of dose per fraction. It therefore remains an open, and significant, question, whether the early highly encouraging results achieved with carbon beams (for example) are a consequence of the higher LET or of the more assertive fractionation scheme applied in most instances. A precedent to this question is the success of high-dose, single-fraction, radiosurgery. Answers to these questions will have a fundamental impact on the applicability and cost-effectiveness of any of the technology choices in radiation therapy.
The cost of proton therapy remains higher than high-technology photon radiation therapy. The costs associated with protons, however, are expected to decrease as the technology matures and becomes more widely available. Interestingly, however, there are already published studies that indicate health care cost savings for the use of protons in pediatric malignancies because of the reduction in the costs associated with managing late complications that are expected to be avoided with the use of protons. Nevertheless, an understanding of where protons and charged particles might be expected to offer the greatest gain over photons will be important from a societal perspective in allowing the most judicious use of a costly resource.
The author have attempted to present an informative monograph on the subject of charged particle radiotherapy that we hope will serve both as an introduction for those new to this field and a useful resource for those involved in use of charged particle radiotherapy in the clinic. We envision a very significant increase in interest in charged particle radiotherapy as the number of facilities around the world increases. We hope that the publication of this work at this exciting period of development in this field will prove to be a helpful resource for the radiotherapy community.
Throughout this book, the author use the term “Gy (RBE)” to refer to the modification of the physical dose of a charged particle by its relative biological effectiveness (RBE). “Gy (RBE)” appears to be the terminology that will be adopted by the International Commission on Radiation Units (ICRU); other terms that have been used in the past include “cobalt Gray equivalent (CGE)” and “Gray equivalent”. Most proton centers have used an RBE multiplicative correction factor of 1.1 when converting physical dose to the RBE-modified dose (i.e. the Gy [RBE]) used for prescriptions in the clinic.
The physical properties of protons and heavier charged particles, whereby dose is largely deposited in the narrow Bragg peak at a fixed depth in tissue without dose beyond this peak, provide clinicians with a tool to sharply conform the radiation dose around the tumor, thereby permitting selective delivery of external radiation to the tumor. It is anticipated that ongoing improvements in tumor imaging with molecular imaging will further improve the clinician's ability to understand where viable tumor cells are and where radiation dose needs to be deposited. Charged particles are ideal tools for taking full advantage of these improvements in tumor imaging and are expected to permit dose painting areas to tumor where hypoxia, accelerated tumor proliferation, or other tumor profiles that might be associated with radiation resistance are imaged.
The precision of dose deposition with charged particles means that radiation doses can be delivered to the tumor with less irradiation to the surrounding normal tissue and permits selective dose escalation to the tumor. Because higher radiation doses to the tumor increase the likelihood of sterilizing the tumor cells and because irradiation of less normal tissue and/or delivery of lower dose to the same or smaller volume of normal tissue result in fewer treatment related complications, protons and charged particles provide the opportunity to improve the therapeutic ratio by increasing the tumor cure probability while simultaneously reducing the risk of normal tissue complications. It is anticipated the use of intensity-modulated proton therapy (IMPT) will further increase this therapeutic ratio.
Interest in the clinical use of protons beams was stimulated by R. Wilson, who in 1946 noted the clinical potential of the physical characteristics of protons. The initial clinical tests were by researchers at facilities originally designed and installed for basic high-energy physics research. Treatments were, as a consequence, much more cumbersome and limited compared to those which could be given in a hospital clinic. The proton beams were limited to a fixed horizontal position, which meant that the patient had to be moved to align the tumor on the trajectory of the beam. This contrasted sharply with the isocentric capabilities of the linear accelerator, which rotates around a point in space and can effectively target any site in the body from an arbitrary direction. For linear accelerator x-ray treatments, the patient is generally in a comfortable supine or prone position on a moveable table, while the machine can be moved to orient the x-ray beam with respect to the target. In proton therapy, patients often had to be immobilized in unusual and difficult-to-reproduce decubitus or angled body positions that were less comfortable and at times limited the choice of beam trajectories. In addition, for many of the proton machines, the beam energy, which defines the depth of the Bragg peak, was limited. Few had sufficient energy to treat all sites in the body. Because of these limitations and the interests of the involved practitioner, the clinical sites that initially received the most interest were uveal melanomas in the eye and base of skull sarcomas. The major emphasis for proton therapy clinical research initially was dose escalation for tumors for which local control with conventional radiotherapy was poor, initially including base of skull tumors, locally advanced prostate cancer, hepatocellular carcinoma, and medically inoperable non-small cell lung cancer.
The development of hospital-based cyclotrons with higher energy beams capable of reaching deep-seated tumors (up to ~34 cm with a 235-MeV beam), field sizes comparable to linear accelerators, and rotational gantries puts proton radiation therapy delivery on par with the photon radiation therapy clinic. Commercial vendors are now able to build these facilities on-time and on-budget and multiple institutions around the world are committing resources to acquiring these facilities. Hence, proton radiotherapy will be available to many more patients and can now be extended to of the full complement of clinical sites. Increasingly, there is interest in protocols aimed at morbidity reduction in those tumor sites in which tumor control with photons is good. Many pediatric tumors fall into this category. It is to be emphasized that dose escalation and morbidity reduction are not mutually exclusive when using protons and that the opportunity for both may be present in any given patient.
Much of the clinical experience to date has been with proton beams and much of this book focuses on the use of the proton beam in the clinic. One property of charged particle dose deposition, the linear energy transfer (LET) or rate of energy loss per unit distance, relates to the biological impact of a particular radiation type in tissue. The radiobiology of protons is similar to that of photons. Photons, protons, and helium ions are therefore considered low-LET, and biologically equivalent, radiation. The adoption of protons by clinicians can therefore build directly upon, and evolve from, prior experience with photons.
Heavier charged particles (neon, carbon) and fast neutrons are considered high-LET radiation. There is an initial increase in the relative biological effectiveness (RBE) with an increase in LET. High-LET radiation response in tissue is less influenced by oxygenation and less sensitive to variations in the cell cycle and DNA repair. The combination of the higher RBE with the highly conformal dose distributions that can be achieved with these particles might be advantageous for treatment of some tumors in the clinic. It should be noted that the disappointing experience with neutrons (with an RBE of 3) in many clinical sites was related to the suboptimal dose distribution that could be achieved with neutrons in the clinic. As a consequence, the observed higher normal tissue complication rates related to the higher RBE effect on normal tissue. It is hoped that these normal tissue complications can be avoided with heavy charged particles because of the inherent ability to precisely control the dose deposition in the patient. The major heavy-particle experience to date has been with carbon beams and this experience will be discussed.
Besides LET, the critical clinical variable is the fractionation schema applied to the treat a particular disease. To wit, the RBE is a function of LET and of dose per fraction. It therefore remains an open, and significant, question, whether the early highly encouraging results achieved with carbon beams (for example) are a consequence of the higher LET or of the more assertive fractionation scheme applied in most instances. A precedent to this question is the success of high-dose, single-fraction, radiosurgery. Answers to these questions will have a fundamental impact on the applicability and cost-effectiveness of any of the technology choices in radiation therapy.
The cost of proton therapy remains higher than high-technology photon radiation therapy. The costs associated with protons, however, are expected to decrease as the technology matures and becomes more widely available. Interestingly, however, there are already published studies that indicate health care cost savings for the use of protons in pediatric malignancies because of the reduction in the costs associated with managing late complications that are expected to be avoided with the use of protons. Nevertheless, an understanding of where protons and charged particles might be expected to offer the greatest gain over photons will be important from a societal perspective in allowing the most judicious use of a costly resource.
The author have attempted to present an informative monograph on the subject of charged particle radiotherapy that we hope will serve both as an introduction for those new to this field and a useful resource for those involved in use of charged particle radiotherapy in the clinic. We envision a very significant increase in interest in charged particle radiotherapy as the number of facilities around the world increases. We hope that the publication of this work at this exciting period of development in this field will prove to be a helpful resource for the radiotherapy community.
Throughout this book, the author use the term “Gy (RBE)” to refer to the modification of the physical dose of a charged particle by its relative biological effectiveness (RBE). “Gy (RBE)” appears to be the terminology that will be adopted by the International Commission on Radiation Units (ICRU); other terms that have been used in the past include “cobalt Gray equivalent (CGE)” and “Gray equivalent”. Most proton centers have used an RBE multiplicative correction factor of 1.1 when converting physical dose to the RBE-modified dose (i.e. the Gy [RBE]) used for prescriptions in the clinic.
Book Details
- Hardcover: 320 pages
- Publisher: Lippincott Williams & Wilkins; 1 edition
- Language: English
- ISBN-10: 0781765528
- ISBN-13: 978-0781765527
- Product Dimensions: 11 x 8.7 x 0.7 inches