Strahlentherapie最新文献

Fast neutron radiotherapy in the United States is entering a new era in which dedicated hospital-based generators with isocentric beam capability are replacing treatment facilities based on fixed beams extracted from physics accelerators. All available clinical data, however, come from the older facilities. The majority of randomized trials conducted in the U.S. have used neutrons in a mixed schedule with photons, in which the aim was to deliver two-fifths of the total dose with neutrons; the neutron dose per fraction was set as the estimated equivalent of 2 Gy photons in terms of late normal tissue injury. Overall treatment time was held constant compared with the control photon therapy regimens (usually six to eight weeks). Random studies of this type showed no evidence of a therapeutic gain in the treatment of advanced primary carcinomas of the head and neck, lung, uterine cervix, or pancreas. A statistically significant benefit in favor of the mixed schedule is presently apparent for local control and survival in patients with advanced prostate cancer, and for clearance of neck nodes in patients with advanced squamous carcinoma of the head and neck. Based on encouraging results in a pilot study of mixed scheduled irradiation preoperatively for bladder cancer, a random study was begun in 1981, but too few cases have been accrued for analysis. Other randomized trials comparing protracted neutron only regimens with photon therapy have been conducted. These were negative for lung and pancreatic cancer, but a suggestion of a therapeutic gain (with small patient numbers) has been observed for treatment of inoperable salivary gland tumors and advanced squamous carcinomas of the head and neck. Two large randomized studies of various neutron doses delivered as a boost to high grade astrocytomas after or concurrently with photon irradiation have failed to define any therapeutic window between tumor destruction and brain necrosis. Based on a reassessment of all the available clinical and radiobiological data, and taking advantage of the greater technical flexibility offered by hospital-based facilities, the strategy of fast neutron therapy for future trials has been changed. In these trials neutrons are being used in a twelve fraction, four week regimen to treat gross disease, with elective therapy being given wherever possible using low LET irradiation. Concomitantly, research is proceeding to define predictors of tumor response to high LET radiations in order to better select patients for fast neutron radiotherapy.

Various preclinical tests have been performed to determine the properties of fast neutrons of a mean energy of 2 MeV produced by an U-235 converter plate in the research reactor of the Technical University of Munich. Experiments have been carried out using two specific beams denoted as RENT I and RENT II (RENT stands for Reaktor Neutron Therapy). RENT II is the unmodified beam with a dose rate of 65 rd/min and a gamma-contamination of nearly 50% in 2 cm depth of a perspex phantom. In RENT I the gamma-component is reduced to 25% after filtration of the beam with 2.5 cm lead, whereas the total dose rate is reduced to 22 rd/min.

82 radioresistant mesenchymal sarcomas localized mainly at the trunk and the extremities have been irradiated with fast neutrons. In all three tumor dose ranges applied (6 to 9.6, 10 to 12.6, and 13 to 19 Gy) alike with 90% of the tumors either complete (congruent to 50%) or partial (congruent to 40%) regressions were observed; only 10% were unresponsive. Further 53 soft tissue sarcomas, showing a spontaneous recurrence rate following local extirpation up to 50%, underwent postoperative prophylactic irradiation with tumor doses of about 10 Gy. In 45 cases surveyed for at least two years, there developed seven (15%) recurrences in the irradiation field. The high regression rate and the good prophylactic effect against recurrences with doses well tolerable, render neutron radiation especially suitable for the treatment of soft tissue sarcomas.

The present day rationale for anticipating a therapeutic advantage of neutrons over X-rays is reviewed. It is based on the following characteristics of tumorous tissue: hypoxia, poor cell cycle redistribution, large repair capacity and rapid growth. It is obvious that not all of the possible reasons why X-ray therapy may fail can be circumvented by the use of neutrons. Therefore the practical consequences of the mentioned rationales must be the planning of randomized clinical trials. With patients selected for poorly reoxygenating tumors, tumors in which clonogens proliferate slowly and others where they grow rapidly and/or show an early regenerative response. Predictive assays for such a selection are, however, only scarcely available and need to be developed to supplement the indication given by conventional staging and grading. Other important consequences of radiobiological considerations are finally concerning treatment strategies. Regardless of the exact dose per fraction chosen, it seems prudent to use relatively low doses per fraction initially to maximize the chance of detecting any benefit inherent in the use of neutrons, before exploring increased doses for reasons of improved cost-effectiveness.

The experiences of the treatment of bladder carcinoma indicated the direction in which the dose optimization program of intraabdominal tumours can be carried out. Small intraabdominal target volumes seem to tolerate doses from 31 to 33 Gy applied in 20 fractions. The best results with local tumour control and low complication rates have so far been reached in carcinoma of the cervix. It has not so far been organizationally possible at SIN to treat with pions on more than four days per week. This restricts changes to the fractionation scheme in the treatment of highly malignant gliomas. An improvement of results could be possible on the basis of experience to date. The significance of a postbiopsy preoperative radiotherapy, of the increase of target volume and the increase of the total dose will be tested in a study by the SAKK (Swiss Group for Clinical Cancer Research).

The rationale for treating all fields every day with photons was reviewed. Since the effects of neutron radiation are much less dependent on alterations of fractionation schedules, and since preferential sparing for late effects is not obtained by fractionation of neutron dose, less convincing reasons exist for treating all fields every day with neutrons. Treating one field/day would not alter the physical dose distribution or overall treatment time, yet still maintain biological homogeneity. Preliminary in vitro experiments support this conclusion.

The results of neutron and neutron boost irradiation of 199 patients with soft tissue sarcomas treated between 1978 and 1983 are presented. The median follow-up period is 42 months. The recurrence free survival rates by last review are 93% for patients with T1 tumours (n = 14), 87% for T2 tumours (n = 84) and 73% for T3 tumours (n = 101). The actuarial survival rates at six years are 77% for T1, 63% for T2 and 34% for T3 tumours (p = 0.018). The actuarial survival rate for the group of patients irradiated after surgery without clinical evidence of residual tumour is 63.8% compared with 30.9% for the group of patients with measurable tumour volume at the beginning of radiotherapy (p = 0.002). The survival rates according to grading are 52% for patients with G1 tumours (n = 44), 54% for G2 tumours (n = 130) and 36% for G3 tumours (n = 25). The morbidity rate of 22% after full neutron irradiation was reduced to 15% by the introduction of a neutron boost. At the present time, the results of this modified treatment are not inferior to a full neutron course. The effectiveness of neutron or neutron boost irradiation in the postoperative treatment of soft tissue sarcomas will be evaluated in a forthcoming EORTC trial.

Neutron therapy started in Orleans in January 1981, after a period of radiobiological investigations [5,6]. Up to December 1984, 437 patients have been irradiated with neutron beams produced by 34 MeV protons on beryllium.

Between March 1978 and October 1983, 65 patients with locally advanced soft tissue sarcomas were treated at the cyclotron of Louvain-la-Neuve. 46 patients are analysed, 19 patients with intraabdominal or intrathoracic lesions are excluded. After "radical surgery" (no "gross tumour" present at the time of neutron therapy), a local control rate of 93% was achieved (25/27 patients) and the survival was 74%. In a second group of 19 patients with incompletely resected, or recurrent, or inoperable tumour, a local control was obtained in four cases (21%), and 13 patients were alive (69%). The follow-up ranged from three to 65 months (mean: 25,9 months). Ten severe complications were observed (22%); they were related to the field sizes, which reflected the local tumour extent.