The paradigm of "more energy is better" is not limited to space travel, and in fact is center stage in a growing debate in the field of radiation oncology.
Editor-in-Chief Chief Innovations Officer, Professor, and Vice President of Cancer Services John Theurer Cancer Center at Hackensack University Medical Center
For decades, these immortal words were used by Captain Kirk of Star Trek when more “energy” was needed to get out of trouble. The paradigm of “more energy is better” is not limited to space travel, and in fact is center stage in a growing debate in the field of radiation oncology. Before I focus on the debate, let me begin by reviewing some elementary physics. A proton is much heavier than an electron and “infinitely” greater in size than a photon. While the quantum mechanics folks will tell us that we cannot truly measure the weight or size of an electron, estimates based on statistical averages put a proton at 1836 times heavier and 104 larger than an electron. To put this into visual perspective, if an electron were the size of a baseball, a proton would be about the size of Yankee Stadium’s entire infield.
As we remember from high school physics, Energy = Mass x C2. Therefore, to get a proton to travel at a velocity approaching the speed of light (C)—the speed at which an electron or photon travels during standard radiation therapy—it is going to take a lot more of a push, and when the proton arrives, it will have a significantly more forceful “punch.”
While working in the Harvard Cyclotron Laboratory in 1946, Robert R. Wilson posited that protons could be used as an energy source to provide therapeutic value. After a period of clinical study using research particle accelerators at the Harvard Cyclotron Laboratory and Massachusetts General Hospital, the first hospital-based proton therapy center opened in the 1990’s at the Loma Linda University Medical Center. Over the past 10 years, several proton beam centers have begun treating patients, and many new centers are now under construction or in the planning phases.
There are several theoretical advantages to using high-energy protons in place of electrons or photons. Protons are not as easily pushed off course due to their relative heavy mass (compared with electrons and photons), considerably reducing lateral side scatter. This could translate into less toxicity to healthy tissue surrounding the tumor. In addition, due to the physics of energy delivery from protons, the maximum energy delivered occurs over a very tight peak at the end of the proton’s range, called the Bragg Peak. The ability to generate greater energy (“more power”) in a defined area has resulted in better clinical outcomes (eg, lower incidence of local recurrence) in several clinical situations including uveal melanomas and unresectable tumors and sarcomas at the base of the skull.
There is little debate regarding the clinical application of this technology in several uncommon malignancies. However, debate has ignited now that protons are being used in a very common malignancy (ie, prostate cancer) with the intent to limit toxicity to surrounding tissue and enhance efficacy. At the root of the debate is the overall cost of constructing new proton facilities. It takes a whole lot of magnets to accelerate and aim a beam of protons streaming at nearly the speed of light. In fact, while a linear accelerator fits comfortably in a relatively small room, a proton facility takes up an entire building. This explains the average construction cost of $100-$180 million for these new facilities.
The ability to generate greater energy (“more power”) in a defined area has resulted in better clinical outcomes.... However, debate has ignited now that protons are being used in a very common malignancy (ie, prostate cancer) with the intent to limit toxicity to surrounding tissue and enhance efficacy.
In a recent comparative effectiveness study involving 12,000 men from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database between 2002 and 2009, Chen and colleagues assessed toxicity and efficacy of different modes of radiation therapy delivery in men with prostate cancer. When compared with conventional conformal radiation therapy or intensity-modulated radiation therapy (IMRT), the analysis showed that the use of proton-beam therapy did not improve outcomes. In fact, of particular concern was the finding that proton therapy was associated with a greater incidence of rectal bleeding. A retrospective analysis cannot be considered definitive. However, the cost of constructing a proton facility must be recovered, which means that the cost of therapy would apparently need to be greater than that of IMRT. Prospective trials are now ongoing to formally compare the efficacy and safety of proton therapy versus photons in men with prostate cancer.
In the end, value-based decision making is essential. Greater cost but less toxicity may warrant use of proton-based therapy. In contrast, there is little room for greater cost and greater toxicity unless efficacy is strikingly better. So, we simply may need to wait for the results of prospective trials before we start routinely asking Scotty to provide us with “more power.”