An old physics joke: A proton walks into a bar and orders a beer. The bartender asks, “Are you sure?” The proton says, “I’m positive.”
There are many ways to kill or destroy a tumor. Our goal is to find methods which are highly effective, have minimal adverse effects, and are hopefully cost-effective at the same time. While we usually focus on surgery and chemotherapy, we should also note the multiple interventions that have been developed in the radiation oncology and interventional radiology worlds, primarily for dealing with localized tumors. Most obvious in this category is the longstanding use of external beam radiation therapy which utilizes photons, dating back to the era of the Curies, but now supplemented by brachytherapy as well as electron beam therapy. Interventional radiologists now also offer various forms of ablation therapy using various modalities for the destruction of the tumor. These forms of ablation include heat (radiofrequency ablation which uses electrical energy), cryoablation (uses extreme cold) or Y90 ablation, among others.
These modalities may offer topics for discussion in this column on another day, but today we address proton beam radiotherapy. While standard radiation therapy uses ionizing radiation to treat tumors, proton beam therapy uses protons, the large positively charged particles in atoms, to do the same. In order to utilize protons for this purpose, a cyclotron is necessary. This is a large, expensive device developed by physicists for the study of subatomic particles and which is utilized for acceleration of particles. The acceleration of protons was first used for therapeutic purposes in the mid-1950s at UC Berkeley. Many of the advances on its use have been developed at Massachusetts General Hospital in Boston as well as in the Soviet Union.
The first successful proton beam radiation center in the U.S. was established at Loma Linda University in California in 1990, followed soon after by a center at MGH. At this point in time, there are 35-40 such centers scattered around the United States. In the tri-state area, there is a proton center at Robert Wood Johnson University Hospital in New Brunswick, and in New York there is the New York Proton Center, a collaboration of Montefiore, Memorial Sloan-Kettering and Mount Sinai.
These centers have been very controversial, with the issue revolving around whether their high cost is justified by significantly improved efficacy. The cost of a single-room proton treatment center runs about $40 million—most of the centers are several rooms; the New York Proton Center is four rooms, which probably required an investment of over $200 million. The upshot of such a mammoth investment is that the cost of treatment with proton beam radiotherapy is consequently high. But even more importantly, it mandates that the specialists at institutions with these centers will perforce recommend proton beam radiotherapy over traditional cheaper external beam radiotherapy so as to recoup these investments.
The key question is: What is the benefit of proton beam therapy over conventional radiation therapy? It can deliver high-dose radiation therapy with a beam that conforms to the shape of the tumor more precisely than can be done with traditional ionizing or photon beam therapy. In addition, when the heavy protons penetrate through tissue to strike the tumor cells, they are stopped by the tumor and so do not penetrate through the tumor to affect the normal tissue on the other side of the tumor, in contrast to regular RT, which passes through the tumor and so can affect and damage normal tissue distal to the tumor. Thus, in theory, proton beam therapy should cause less damage to surrounding normal tissue while delivering similar or higher doses of radiotherapy to the tumor.
Proton beam RT has been preferentially used for tumors that benefit from especially high doses of radiation, which this modality can deliver with less damage to surrounding tissue. Thus, it has been used for uveal melanoma or other eye tumors such as retinoblastoma, unresectable sarcomas and base-of-the-skull tumors. A second area of use is, as noted previously, tumors where less damage to normal tissue is desired, as in prostate tumors or childhood malignancies.
Its use for most tumors lacks definitive evidence of superiority as could be derived or demonstrated by randomized trials. It does seem that it is superior for the tumors I described above, which require particularly high doses in limited areas, such as ocular tumors. The tumor of most interest is prostate cancer because of its high incidence. Several observational studies have compared proton beam to ionizing radiation for its treatment, and while there may be some increased toxicity in the short term for ionizing beam radiation, this abates with time; overall the two modalities seem equivalent in efficacy, but the cost is twice as high for proton beam RT. The guidelines of the American Society of Clinical Oncology and of the American Society for Radiation Oncology both recommend only using it in experimental settings for prostate cancer.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
