Introductory Chapter: Proton Therapy – The Promise is Moving to an Enterprise Function

1. Introduction

Radiation therapy has become increasingly important in the care of patients with cancer. Progress in radiation therapy technology has provided more opportunities to treat patients with curative intent. In multiple disease sites, patients with oligometastatic disease are treated with comprehensive radiation therapy to all sites of disease at presentation with improved outcomes. Common sense would argue that as additional sites of disease are treated in an increasingly comprehensive manner, more normal tissue would be unintentionally treated as part of the radiation therapy care plan which in turn could augment sequelae of management and limit the application of additional therapies. Mitigating this issue with improved radiation therapy treatment technology would serve to improve outcomes by assuring full dose to tumor target and decreased dose to normal tissue. Compared to photon-directed radiation treatment, proton-directed therapy can provide uniform radiation dose to tumor targets with decreased dose to normal tissue, thus improving the therapeutic index for patient care. The goal of radiation therapy is to provide tumor control with limited risk of injury and proton therapy serves as an ideal platform to ensure optimal outcomes. Based on the fundamental understanding that ionizing radiation transfers energy into tissues resulting in DNA damage leading to tissue injury and cell death, identifying pathways to limit normal tissue injury, and enhance tumor cell kill with systemic therapies improves patient outcomes. Because of the inherent capability of proton therapy limiting dose to normal tissue, defining pathways to facilitate the deployment of proton therapy worldwide will serve to improve patient outcomes moving forward. This has to be balanced with the cost of production and availability of expertise with the appropriate training to both initiate and maintain a proton program [1, 2, 3, 4, 5, 6].

2. History

As is well demonstrated by atomic theory, atoms are comprised of particles with a positive charge (protons), a negative charge (electrons), and a neutral charge (neutrons). Robert Wilson was the first to recognize the medical application of proton therapy. Wilson recognized that protons exhibit a progressive change in velocity as they migrate through tissue and culminate in what is termed a “Bragg peak” with a rapid drop off in energy after the peak. The working premise was that by harnessing the geometry of the pathway and Bragg peak, protons could be used to target disease housed within and in close approximation to normal tissue. Because of the decrease in energy beyond the peak, normal tissue beyond the peak would only receive a nominal dose, unlike treatment plans using photons. His vision was prescient and far ahead of its time and remains a fundamental principle in patient care today with particle therapy.

Radiation therapy has a rich scientific history. William Roentgen developed a cathode ray tube which led to the discovery of X-rays. One of his many primary findings was that an X-ray can pass through solid objects however the fact the X-ray is significantly titrated by bone and metal remains a fundamental principle of radiology practice to this day. Becquerel discovered radioactivity and Marie Curie discovered radium which would build the bridge to medical sciences. From their seminal work, both diagnostic and therapy programs matured into now what is an extraordinary industry producing devices that generate high-energy beams re-purposed in a nimble and efficient manner for direct patient care. Expertise in medical care and medical physics has provided a pathway for unprecedented process improvements in patient outcomes with treatments today that are highly sophisticated, modulated by dynamic multi-leaf function during therapy, and aligned with targets with efficient and modern daily image guidance. The technology improvements within the past two decades are extraordinary with modern trainees unfamiliar with the processes and limitations of treating patients in the past. Applying the technology success in photon care to proton care is becoming an important next step for proton manufacturers and will lead to moving proton care into a worldwide enterprise function providing cost can be controlled and continued miniaturization of proton units can be designed and retrofitted into existing therapy vaults for cost savings [1, 2, 3, 6].

3. Future directions

To make proton care more available to the general population of oncology patients, continuous process improvements are required to both facilitate patient care and make proton care available to the global oncology community. Initial proton treatment facilities had multiple therapy gantries associated with the cyclotron/synchrotron and required large building footprints for treatment execution. Today, treatment facilities are being designed with less cost in a building footprint similar to a photon accelerator. This has led to significant changes in how proton centers are both designed and distributed worldwide. Single gantry systems developed by multiple vendors have significantly reduced the cost of developing a proton center. Currently, there are approximately 100 proton centers operational worldwide with more than 30 centers in Europe. The Roberts Proton Center at the University of Pennsylvania is one of the largest centers in the world housing multiple gantries for patient care. Washington University of St. Louis houses a single gantry system with a cost significantly less than a larger center making proton therapy accessible to many institutions and patients worldwide. Washington University has recently installed a second single gantry system due to the need to provide service to the larger community. The continued miniaturization of proton technology will continue to make the product less expensive bringing the technology within reach for institutions less capable of purchasing other larger systems. Vendors evaluating the possibility of placing a unit in an existing photon therapy vault. This effort includes clever design of the unit and novel table designs to treat patients in multiple positions with a table which can support patients in multiple sitting positions. These efforts represent significant advances in engineering making particle therapy available to an increasing number of institutions worldwide and accordingly, making proton therapy available to more patients. The transition to smaller, more affordable, units will provide a pathway to global applications of proton therapy. Proton manufacturers are working to bring all of the important elements of modern photon care into proton therapy treatment execution including image guidance and multi-leaf-based intensity modulation treatment execution. Aligning and coupling proton care treatment strategies with processes well known to photon physics teams and radiation therapists facilitates the transition of treatment staff to care for patients being treated with proton plans. As engineering is perfected, costs will decrease as the deployment of proton units moves to an enterprise level of distribution [6].

The types of patients and disease sites treated with proton therapy are rapidly increasing at an enterprise level. With the larger, more cumbersome early proton tools, beam compensation processes had to be applied on a daily basis for patient care and this served to limit the patient population treated and managed with proton care. Initially lesions in the central nervous system, then less amenable to surgical intervention including pituitary disease, were treated with protons. As facilities have increased in number and the patient care process in proton therapy delivery have become nimble, nearly every disease site in the treatment of the modern oncology patient has benefits when treated with protons as dose to normal tissue can be titrated in all body sites. Protons are no longer an eclectic therapy used in limited and selected disease sites. In adult oncology central nervous system, head/neck, thorax, upper/lower abdomen, pelvis, and extremity patients are now treated with proton therapy. Protocols are currently active comparing proton and photon care in multiple disease sites with tumor control and normal tissue endpoints designed to determine which sites benefit most from proton care. There is significant interest in expanding the use of proton applications in pediatric oncology patients. With 25% of pediatric oncology population of patients afflicted with disease in the central nervous system, proton applications are highly attractive. With modern imaging tools, the disease can be targeted with increasing accuracy further supporting the application of proton therapy with normal tissue conformal avoidance. Thoracic, abdominal, pelvic, and extremity disease sites in the pediatric population can be targeted with improved normal tissue conformal avoidance. In selected protocols in the Children's Oncology Group (COG), a significant percentage of patients treated with radiation therapy are treated with protons reflecting increased utilization of proton therapy worldwide [4, 5, 6].

Patients can be successfully treated with radiation therapy with photons or protons. Because of the improved dose distribution of protons to normal tissue, protons present a theoretical advantage to photons with respect to radiation dose to normal tissue. This can have an important consequence for patient management moving forward as radiation dose to normal tissue has an impact on supplemental care including targeted and systemic management. Continued process improvements including progress in miniaturization will further support the application of protons into daily patient care management.

In this chapter, we present theoretical and practical aspects of proton care management which have importance moving forward for proton application in patient care. Hopefully, with these and other changes, proton can move worldwide into enterprise function.