Strahlentherapie最新文献

Fractionated precision high-dose proton radiotherapy has been carried out at the Harvard Cyclotron Laboratory (HCL) since 1973, in a collaborative effort with the Radiation Medicine Department of Massachusetts General Hospital (MGH) and the Retina Service of the Massachusetts Eye and Ear Infirmary (MEEI). This paper will discuss proton treatment in general, treatment planning procedures, and results to date in major patient categories. 846 patients have been treated with fractionated proton therapy at the Harvard Cyclotron, with normal tissue and tumor responses consistent with an RBE of 1.1 for the proton beam. Proton beam therapy is the treatment of choice for patients with uveal melanomas, and chordomas and chondrosarcomas involving the skull base and cervical spine. Improved dose distribution possible with protons have allowed greater doses than are given conventionally to be delivered to patients with prostatic carcinoma, head and neck malignancies, ano-rectal cancers, and retroperitoneal tumors. Doses employed have been usually 10 to 20% greater than normally would be delivered in our department to such tumors. Generally, local control rates have been good.

From 1957 to 1968, the 230-cm synchrocyclotron at the Gustaf Werner Institute was used for clinical tests with a 185 MeV proton beam. The radiotherapeutic research was part of an extensive research programme in physics, chemistry, biology and medicine. Only a small series of patients were treated. A brief review of the early development and clinical experience of the cyclotron activities at Uppsala from 1957 to 1968 is given. The former accelerator is now being converted. Beams are expected to be available in the new radiotherapy treatment rooms in 1986. Plans for the new facilities with special reference to alternative methods of proton acceleration and beam transport, i.e. fixed beams or an gantry system are presented. The corresponding activities at the Institute of Theoretical and Experimental Physics (ITEP) in Moscow are also referred to thanks to a bilateral research programme which has existed in the past and from which the Uppsala group has benefited greatly.

Part of the clinical results from the "EORTC Heavy-Particle Therapy Group" are reviewed (September 1984). Fast neutrons can bring a significant benefit, compared to conventional photon (or electron) techniques, in well defined patient series. A benefit for neutrons is observed, in Hammersmith and in Amsterdam, for locally extended salivary gland tumours. Soft tissue sarcomas can also be considered as a good indication for neutron therapy, especially when they are slowly growing and well differentiated, as shown in Essen, Hammersmith and Louvain-la-Neuve. Neutrons can bring an advantage in the treatment of some melanoma patients as shown in Hammersmith. For locally advanced prostatic carcinoma, better results for neutrons are shown in Hamburg and Louvain-la-Neuve. These data are similar to those observed in the United States from the RTOG studies. Due to a reduced differential effect between tissues after neutron treatment, irradiation of large volumes of normal tissues, at high neutron dose, should be avoided. Different possible combinations between neutrons and photons (boost, mixed schedule) are discussed.

In Hamburg since 1976 to 1980 we have treated 328 patients with fast neutron (DT, 14 MeV) and after reconstruction of the generator further 69 patients in 1984. The therapy with DT-neutrons had the best curative effect on high differentiated tumors. With the standard dose of 16 Gy in four weeks or--treating tumors in radiosensitive organs like brain and intestine--with a photon-neutron schedule, we have seen no necroses in normal tissues. The rate of medium or slight subcutaneous fibroses is not more than 10%. The local effect on tumors in our pilot study has been better than with megavoltage therapy in invasive thyroid cancer, prostate cancer stage C, soft tissue sarcoma and also in rectum-carcinoma. The best results have been achieved with neutrons only, but a photon-neutron schedule may be more effective as megavoltage therapy only. With our DT-neutrons we find some indications for better results than with megavoltage therapy if we use sophisticated treatment planning and if we strictly observe the tolerance dose of the different tissues and organs. The therapeutic index of our monoenergetic DT-neutrons is higher than with cyclotron-produced neutrons.

By means of positioning and fixation aids, the precision and reproducibility of irradiation fields in radiotherapy of malignant tumors of the head and neck can be considerably improved. Face masks made of different synthetic materials have proved to be a practicable solution of this problem. In our hospital we have developed and tested a simple and not expensive possibility of manufacturing the masks with "Baycast" (producer: Bayer AG Leverkusen). The material is generally well tolerated by the patients, and the head is sufficiently fixed. An increased incidence of radiogenic dermatitides is caused by the overlapping of the depth dose of the Co-60 gamma radiation due to additional secondary electrons emanating from the mask material. This effect can be partly prevented by cutting out the irradiation fields in the masks.

New possibilities for radiotherapy of bronchial carcinomas are provided by the combined application of the recently introduced afterloading method used hitherto in the treatment of stenosing processes of bronchial carcinomas and the neodyme-YAG laser which opens the stenosis in such a manner that the afterloading probe can be inserted. This new method allows to perform without complications or disadvantages further combined therapies such as percutaneous irradiation (telecobalt, linear accelerator or betatron). An irradiation scheme leading to a decisive tumor regression can be established due to the fast reventilation of the lung obtained by both methods. Surprisingly, three patients could be submitted despite the small-field radiotherapy to rather important lung operations such as lobectomy and pneumonectomy which were performed without complications or disadvantages. The patients were not operable without laser and afterloading therapy. This method was applied several times in the treatment of other diseases such as oesophageal cancer and stenosing cancer of the antrum. In these cases, a normal ingestion due to tumor regression was obtained rapidly.

Carcinoma of the common hepatic bile duct or common bile duct were treated by interstitial irradiation with gold seeds using the percutaneous transhepatic drainage partly boosted by external irradiation. The interstitial dose of 50 Gy was given in two applications and 40 Gy by linac. Twice histological examination showed wide tumor destruction of local irradiation, but also much more tumor extension than seen before by diagnostic investigation. Mostly the therapy is only palliative because of the infiltration of liver and lymph nodes.

By an irradiation of the neurocranium with doses from 12 to 30 Gy during the combined treatment of ALL in children, an essential reduction of the leukemic manifestation on the meninges as well as an improved curability have been achieved during the last few years. The precision of the irradiation technique is of vital importance, i.e. the occurrence of recurrences on the central nervous system during complete remission after skull irradiation are preponderantly due to a defective irradiation technique. The important factors are a daily reproducible positioning and fixation of the head in an irradiation mask and the adjustment within three dimensions by means of a laser light system. Only cobalt-60 gamma radiation or the ultrahard photons of a linear accelerator with an energy of 4 to 6 MV should be applied. The irradiation is performed with laterally opposite, coplanar and coaxial fields in an isocentric adjustment. The field shape is regulated by individual absorbers adjusted under visual control in a defined position to the patient on a plexiglas plate at the therapy simulator. In order to guarantee an homogeneic dose also to the meninges situated at the field borders and to prevent a "geographic miss", the field borders should exceed the cranial calotte by 1 to 2 cm at the frontal, vertical and occipital side. At the base of the skull, special consideration must be given to a sufficient irradiation of the retrobulbar spaces, the frontal meninges situated in the region of the lamina cribrosa and the temporal meninges situated in the region of the deep inner cranial fossae. The dose specification is made in the central ray in the center of the skull. Generally single doses of 2 Gy and weekly doses of 10 Gy are applied. The total dose depends on age, risk group, and treatment aim. Recent studies indicate that in case of simultaneous intrathecal administration of methotrexate, the single dose can be reduced from 1.8-2.0 Gy to 1.2-1.5 Gy and the total dose from 24 Gy to 18 Gy without any unfavorable effect on the rate of recurrences at the central nervous system and the survival rate. Within the scope of an aggressive combination therapy, this self-restraint of the radio-therapeutist is of great importance with regard to acute and chronic complications in the brain and the growing skeleton.

Monolayer cells of a Harding-Passey melanoma (HPM 73 cells) which were irradiated during the phase of exponential growth with an X-ray dose of 4 Gy of 8 Gy did not show any ultrastructural changes four days after 4 Gy, whereas cells irradiated with 8 Gy showed slight damages such as swollen mitochondria and vacuoles. As shown by the electron microscope, a sole addition of a sublethal quantity (6 X 10(-6) M) of quinacrine (Atebrin) or chloroquine (Resochin) did not lead to significant cell modifications. Those melanoma cells with were pre-irradiated with 8 Gy and then incubated during four days with 6 X 10(-6) M of quinacrine (Atebrin) or 6 X 10(-6) M of chloroquine (Resochin) showed severe damages. There was an increased rate of vacuoles and segregational structures in cytoplasm. The mitochondria were increased and swollen and the cellular surfaces had less microvilli. However, microtubules and microfilaments seemed more distinct. The melanin concentration increased under this treatment. The cell nuclei were increased in volume and seemed to be rather void of chromatin. These reactions of cells on quinacrine (Atebrin) and chloroquine (Resochin) are explained by the known inhibition effect exerted by these substances on DNA synthesis, especially as far as the processes of DNA reparation are concerned. The changes of the microtubule-microfilament system could be due to a correlation with the increase of digestive intracellular processes connected with the catabolism of radiation-damaged structures.