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Three patients have been treated with 160-MeV protons combined with high-energy photons to examine the advantages and difficulties associated with the clinical implementation of a program of large-field, fractionated-dose, proton-radiation therapy. We have found it necessary to: 1) obtain an accurate three-dimensional determination of the treatment volume including the density of all tissues in the beam path; 2) construct an adequate bolus to compensate for tissue heterogeneities; 3) use much more precise and accurate immobilization and patient positioning devices than used in photon irradiation; 4) treat with both protons and photons so as to keep the skin dose within an acceptable level. In tissues without significant inhomogeneities due to bone and air spaces we have delivered a well-defined dose to involved tissues while sparing distal sensitive structures. However, in those regions where there is much “fine structure” of tissue density, it has been difficult to compensate satisfactorily for the inhomogeneities.

The authors' method for predicting, and compensating for, the effects of surface irregularities and tissue heterogeneities in proton radiation therapy was evaluated by comparing the predicted and measured dose distributions. Two heterogeneity configurations in a D-shaped water-filled phantom were handled in exactly the same way as patients. Target volumes were designated on thin-section CT scans, a single en face portal was defined, compensating boli were designed and made, and the dose distribution behind the phantom measured and compared with that intended. The compensation was accurate to within 1 mm for the phantom with a single air heterogeneity and to within 2.5 mm for the phantom with multiple bone and air heterogeneities. The bolus and phantom were misaligned by 3 mm and the dramatic change in the dose distribution demonstrated the need to address the problems of patient motion and imperfect distribution demonstrated the need to address the problems of patient motion and imperfect immobilisation through compensator design. A philosophy of 'expanding' the bolus is described, and dose distributions measured with the 'expanded' boli indicate that target volume treatment can be assured within prespecified repositioning and motion uncertainties. The uncertainty in the alignment of bolus and heterogeneities leads to corresponding uncertainty in the penetration of the protons. Ranges within which they will stop are calculated and shown to encompass adequately the measured distributions in both the aligned and misaligned cases.

From February 1981 to January 1984, 20 patients with a tumor of the upper clivus received proton irradiation at the Harvard Cyclotron Laboratory. For 15 patients with known neurovisual status (including visual acuity, color vision, visual field, and fundus examinations) we obtained a cumulative dose-volume histogram (DVH) of the optic nerves (ON) and the optic chiasm. The prescribed tumor doses ranged from 66.6 to 74.4 Cobalt Gray Equivalent (CGE) with a daily fraction size of 1.8 to 2.1 CGE. CGE is used because modulated protons have an RBE of 1.1 compared to 60Co. The follow-up ranged from 30 to 68 months (median 52). Two patients developed, 10 and 36 months post irradiation, a progressive visual deterioration affecting both eyes. This was attributed to an ON and a chiasm injury in one patient and to bilateral ON injury in the other patient. In the first patient, the dose-volume analysis indicated that approximately half of the ON and of the chiasm had received 65 CGE and 55 CGE, respectively. In the second patient, it indicated that a quarter of the left ON (LON) had received 55 CGE whereas the dose to the right ON (RON) was significantly less. This patient had diabetes mellitus which may be a predisposing factor. From this study, a complication rate of 20% (1/5) is observed when a substantial portion of the ON is taken to 65 CGE, while it doesn't exceed 12.5% (2/16) and 7.5% (1/13) at 55 CGE for the ON and for the chiasm, respectively. This suggests a tolerance dose implying a 10% rate of major complications close to 55 CGE. When a tumor requires a high radiation-dose, the exclusion of these structures at 55 to 60 Gy is recommended.

Except for electrons, the particles which have been accelerated to high energies by machines such as cyclotrons or Van de Graaff generators have not been directly used therapeutically. Rather, the neutrons, gamma rays, or artificial radioactivities produced in various reactions of the primary particles have been applied to medical problems. This has, in large part, been due to the very short penetration in tissue of protons, deuterons, and alpha particles from present accelerators. Higher-energy machines are now under construction, however, and the ions from them will in general be energetic enough to have a range in tissue comparable to body dimensions. It must have occurred to many people that the particles themselves now become of considerable therapeutic interest. The object of this paper is to acquaint medical and biological workers with some of the physical properties and possibilities of such rays. To be as simple as possible, let us consider only high-energy protons: later we can generalize to oth...

Assessment of the available data indicates that proton radiation therapy has more to offer the patient than existing x-ray therapy. The physical properties of proton beams which allow the major fraction of the dose to be confined to a designated volume are reviewed. Dose delivery schemes employing protons are discussed and treatment plans including dose distributions are compared for protons and x-rays.

This paper presents a specialized medical accelerator facility designed for proton radiation therapy and for production of short-lived nuclide-labelled radiopharmaceuticals. General features of the facility structure, the choice of principles of beam delivery, physical and technical problems connected with clinical work, and biomedical research are discussed.

Physical, technical, radiological, and clinical status of proton therapy is reviewed. Protons produce effects similar to those of x rays, but dose distribution and range make protons more flexible and useful therapeutically. The ability to confine the major fraction of proton absorbed dose to a designated volume allows the decrease of dose to normal tissue or the increase of dose to the cancer. Improved dose distribution is quantified by determining the ratio of normal tissue dose for x rays to that for protons in different treatment plans. Normal tissue integral dose from x-ray therapy is generally 2 to 5 times as high as that anticipated from proton therapy.