Andreas Koehler

Range Modulators for Protons and Heavy Ions

Abstract A series of range modulator wheels has been developed to modify the Bragg peak of the 160 MeV proton beam at the Harvard Cyclotron Laboratory. Flat depth-dose distributions up to 15 cm in extent have been produced. Ease of construction and inexpensive assembly recommend the design for use in other heavy particle beams.

Long-term results of proton beam irradiated uveal melanomas

The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis.

Definitive radiation therapy for chordoma and chondrosarcoma of base of skull and cervical spine.

: Proton-beam radiation therapy has been developed for the treatment of chordomas or sarcomas of bone or soft tissue that abut the central nervous system. The authors report the results of treatment of 10 patients, six with chordoma, three with chondrosarcoma, and one with a neurofibrosarcoma. Local control has been achieved for all patients (with, however, one marginal failure) with a follow-up period ranging from 2 months to 6 years. High doses of radiation, up to 76 Cobalt Gray Equivalents (CGE), have been delivered without significant morbidity. In particular, no neurological sequelae have been observed.

Flattening of proton dose distributions for large‐field radiotherapy

Methods for obtaining flattened charged-particle dose distributions over large areas are described. The system being used at Harvard for proton radiotherapy is discussed in detail. It is an extension of usual multiple-scattering techniques to include blocking out some of the central peak, followed by rescattering to fill in the profile, resulting in flat distributions up to 30 cm in diameter. The unusually long source-to-skin distance (4.6-m SSD) plus the small lateral spread (2 mm rms) from multiple scattering in the patient results in little divergence of the beam throughout the treatment volume.

Proton Beam Irradiation: An Alternative to Enucleation for Intraocular Melanomas

Proton irradiation was used in the treatment of uveal melanomas in 36 eyes. The average follow-up period was 16 months. One patient developed metastatic disease and died. No eye has been enucleated and tumor regression has been observed in all 22 eyes with a follow-up of more than 12 months. This type of treatment offers definite advantages over previously used methods, can be used for the treatment of relatively large melanomas, and should be considered before enucleation.

Multiple Coulomb scattering of 160 MeV protons

Abstract We have measured multiple Coulomb scattering of 158.6 MeV protons in fourteen materials from beryllium to uranium including brass and several plastics. Targets ranged from thin (negligible energy loss) to very thick (greater than the mean proton range). The angular distribution was measured by means of a single diode dosimeter scanned typically over two decades of dose falloff. Each data set was fitted with a Moliere scattering distribution (using Bethes tables) to extract a characteristic angle θM as well as a Gaussian distribution to extract a characteristic angle θ0. As expected in the small angle region, the Gaussian fits about as well as the Moliere shape. The θM values were compared with Molieres predicted value ( χ c B 2 ) including Fanos correction for scattering by atomic electrons and using Molieres formalism to account for energy loss and/or compound targets or mixtures. The distribution of the deviation from theory for 115 independent measurements is approximately normal, with a mean value − 0.5 ± 0.4% and an rms spread of 5%. The θ0 values were compared with Highlands formula and with an “improved Highland” formula of Lynch and Dahl, using our own generalization to thick targets. The overall accuracy of Highlands formula is slightly worse than that of Moliere theory. The distribution of the deviation from theory for 115 independent measurements is normal, with a mean value − 2.6 ± 0.5% and an rms spread of 6%. The Lynch formula gives nearly the same average statistics though details of the fit are different. Some data were taken for very thick targets (thickness greater than 97% of the mean proton range) where only a fraction of the incident protons emerge. Here the characteristic angle appears to level off or even to fall slightly with target thickness perhaps due to the filtering out of large-angle protons. These measurements are presented but were excluded from the comparison with theory. We have reviewed six other published proton measurements, partially reanalyzing four whose authors claimed that Moliere theory either did not apply (because of thick targets) or was incorrect. These experiments range from 1 MeV to 200 GeV incident energy. Averaging each measurement including our own over everything but target material we obtain 39 independent measurements of the deviation from theory whose distribution is normal with a mean value − 0.3 ± 0.5% and an rms spread of 3%. We conclude that Moliere theory with the Fano correction is accurate to better than 1% on the average for protons. Systematic discrepancies on the order of a few percent with target thickness and/or target material cannot be ruled out at present. In particular there is some indication that the theory may be ≈ 4% high for the highest-Z materials.

Relative biological effectiveness of modulated proton beams in various murine tissues

The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.

Current Results of Proton Beam Irradiation of Uveal Melanomas

Proton beam irradiation has been used for the treatment of 241 uveal melanomas over the past 7 1/2 years. Twelve melanomas (5%) were small, 99 (41%) medium, 103 (43%) large and 27 (1%) extra-large melanomas. The mean length of follow-up was 21 months and the median 15 months. Ninety-four percent of the treated lesions with a follow-up more than two years and 65% of tumors with shorter follow-up showed regression. The most recent visual acuity was 20/40 or better in 47% and 20/100 or better in 66%. Ten eyes were enucleated because of complications (9) or continued tumor growth (1). Thirteen patients developed metastases from 4 to 50 months of treatment. Our data indicate that proton irradiation can be used to treat melanomas of various sizes and in a variety of locations, and preliminary results suggest that proton therapy has no deleterious effect on the likelihood of the development of metastases.

Visual outcome after proton beam irradiation of uveal melanoma

Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66-10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less in height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63-4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results.

The Risk of Enucieatlon after Proton Beam Irradiation of Uveal Melanoma

Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1% by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation.