Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma.

PURPOSE: This study reports local tumor control and survival after proton beam radiotherapy (PBRT) of uveal melanoma. It identifies the risk factors for local tumor-control failure and for ocular tumor-related death. It presents the improvements implemented to increase the rate of local tumor control, and compares the survival rate of patients with locally controlled tumors to those of patients who had to receive a second treatment. PATIENTS AND METHODS: We have treated 2,435 uveal melanomas with PBRT between March 1984 and December 1998. Data were analyzed as of September 1999. Patients' age ranged from 9 to 89 years; there were 1,188 men and 1,247 women. The largest tumor diameter ranged from 4 to 26 mm, and tumor thickness from 0.9 to 15.6 mm. Median follow-up time was 40 months. RESULTS: Local tumor control probability at 5 years was improved from 90.6 +/- 1.7% for patients treated before 1988, to 96.3 +/- 0.6% for patients treated between 1989 and 1993, and became 98.9 +/- 0.6% for patients treated after 1993. Among 2,435 treated patients, 73 (3%) had to receive a second treatment because of tumor regrowth. Cause-specific survival at 10 years was calculated to 72.6 +/- 1.9% for patients with controlled tumors compared to 47.5 +/- 6.5% for those with recurrent tumors. CONCLUSION: Reduced safety margins, large ciliary body tumors, eyelids within the treatment field, inadequate positioning of tantalum clips, and male gender were identified to be the main factors impairing local tumor control. The improvement of local tumor control rate after 1993 is attributed to changes implemented in the treatment procedure. Our data strongly support that the rate of death by metastases is influenced by local tumor control failure: improvement of the local tumor control rate results in a better survival rate.

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

The exchange of radiotherapy data as part of an electronic patient-referral system.

PURPOSE: To describe the implementation and use of an electronic patient-referral system as an aid to the efficient referral of patients to a remote and specialized treatment center. METHODS AND MATERIALS: A system for the exchange of radiotherapy data between different commercial planning systems and a specially developed planning system for proton therapy has been developed through the use of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the cooperation of the different TPS manufacturers, the number of data sets defined for transfer has been restricted to the three core data sets of CT, VOIs, and three-dimensional dose distributions. As a complement to the exchange of data, network-wide application-sharing (video-conferencing) technologies have been adopted to provide methods for the interactive discussion and assessment of treatments plans with one or more partner clinics. RESULTS: Through the use of evaluation plans based on the exchanged data, referring clinics can accurately assess the advantages offered by proton therapy on a patient-by-patient basis, while the practicality or otherwise of the proposed treatments can simultaneously be assessed by the proton therapy center. Such a system, along with the interactive capabilities provided by video-conferencing methods, has been found to be an efficient solution to the problem of patient assessment and selection at a specialized treatment center, and is a necessary first step toward the full electronic integration of such centers with their remotely situated referral centers.

Effects of respiratory motion on dose uniformity with a charged particle scanning method.

A three-dimensional spot-scanning technique for radiotherapy with protons is being developed at the Paul Scherrer Institute. As part of the effort to optimize the design and ensure clinically useful dose distributions, a computer simulation of the dose deposition in the presence of respiratory motion was performed. Preliminary experiments have characterized the proton beam and the scanning procedure. Using these parameters, the computer program calculated the dose within a uniform volume of water in the presence of respiratory motion. Respiration amplitude, respiration period, respiration direction, number of fractions, size and position of the beamspots and rescanning multiplicity were systematically varied and the effect on the dose distribution determined. The dose uniformity is very dependent on the direction of the respiration relative to the three independent beam scanning directions. The dose uniformity decreases with increasing respiration amplitude, but has little response to changes in respiration frequency. Rescanning the volume, such as with fractionation, improves the dose uniformity roughly as the square root of the number of fractions. Broad, Gaussian beams result in better dose uniformity than narrow, sharply delineated ones, but produce slower dose fall-off at the edges of the scanned volume. Results of this work are being incorporated into the design of the system.