Klaas Breur

Observations on Pulmonary Metastases in Patients After Single Doses and Multiple Fractions of Fast Neutrons and Cobalt-60 Gamma Rays

Abstract Pulmonary metastases have been irradiated with single and fractionated doses of fast neutrons and cobalt-60 gamma rays. The response to radiation was measured on volume changes of the lesions and thus RBE values could be derived. A correlation was found between grading of the tumour and volume doubling time and also between RBE and volume doubling time. This suggests an advantage for high LET radiation of slowly growing, well differentiated tumours. Furthermore the RBE for multiple fractions tends to be higher than for single doses. Calculation of the N exponent of the Ellis formula indicated that hardly any shoulder exists when neutrons are applied.

The value of postoperative radiotherapy as an adjuvant to radical neck dissection

In this study the results of combined radiotherapy and surgery are compared with the results of surgery alone in patients with neck node metastases from squamous cell carcinomas of the head and neck region. Postoperative radiotherapy decreases the recurrence rate in the neck, especially in cases with histologically established extranodal spread. Results of preoperative radiotherapy were similar to those of irradiation after surgery. Postoperative radiotherapy is favored, because it allows a selection of patients for extra treatment on the base of prognostic information, provided by the histologic characteristics of the neck dissection specimen.

Growth rate and radiosensitivity of human tumours. II. Radiosensitivity of human tumours.

Pulmonary metastases from different types of tumour in Man show constant growth rates when measured accurately on successive roentgenograms of the chest. The influence of ionizing radiation on these metastatic tumours could be shown very clearly. Fractionated irradiation resulted in a concentric reduction in the size of the metastases, the outlines of which remained remarkably well defined. This made it possible to calculate the percentage of reduction in volume by measuring the change in diameter. Data on such pulmonary metastases in sixteen of our patients were suitable for quantitative analysis. It was found that volume reduction became evident a few days after the first dose was administered. Repetition of the same daily dose caused percentages of reduction, giving an exponential survival curve. After the last dose of a series was given, the tumour resumed in growth immediately, or at least within a few days, at approximately the same rate as before irradiation. The surviving fractions found in these cases did not conflict with the assumption of an exponential survival curve, as constructed by Elkind for fractionated irraditions of cell cultures. In this way, the mean lethal dose D37 defined as the dose leaving 37 per cent of the original volume capable of resuming growth, could be calculated for these irradiations, in which daily doses of 100–150 rads were applied using 250 kV roentgen and Cobalt-60. The results showed wide variations in radiosensitivity amongst tumours of different types (Table 1). Values of D37 extending from 300 up to 2550 rads were encountered. These differences, which correspond to a factor of 8·5 cannot be explained by the assumption that all cells have the same intrinsic radiosensitivity and that all differences observed are caused by differences in oxygen tension in tissues. Good correlation was found to exist between the radiosensitivity (D37) and the growth rate of a tumour, expressed in terms of the doubling time, T2. For all cases, the equation log D37 = 1·780 + 0·652 log T2 fits the data within fair limits. Excluding the value of D37 for two tumours, i.e. those with the lowest growth rate (T2 > 150 days), all value s of D37 fitted well in a linear correlation according to the equation, D37 = 220 + 10 T2. Possible explanations of the phenomena found are discussed, taking into account the concepts of modern experimental radiobiology. The significance of these relationships for clinical radiobiology and the practice of radiotherapy is considered. The possibility of estimating the lethal dose for a tumour if its volume and growth rate are known is of particular interest. Many additional investigations in various fields will be required to reach this goal, however.

Radiotherapy of lymph node metastases in patients with squamous cell carcinoma of the head and neck region

The results of radiotherapy alone in 233 patients with lymph node metastases of squamous cell carcinoma in the head and neck region were examined. It appeared that the recurrence rate in the neck was mainly related to: localization of the primary tumor; the recurrence of the primary tumor; the radiation dose; and the presence of a residual palpable tumor mass in the neck 6 weeks after radiation. The optimum radiation dose was about 2000 ret. An isoeffect curve was calculated, which differed only slightly with the nominal standard dose (NSD) formula. Elective irradiation of the contralateral neck appeared to diminish the outgrowth of neck node metastases at the side. Changes in the radiation treatment in the last treatment period, such as a higher radiation dose and a larger treatment area, resulted in a lower recurrence rate for the neck node metastases, and also in a higher survival rate.

Results of fast neutron teletherapy for locally advanced head and neck tumors

Abstract An analysis is given of the results of fast neutron therapy for locally advanced tumors of the head and neck region. All patients were treated five times per week with a 14 MeV d+T neutron beam and received dosages of about 19 Gy nγ . The persisting complete regression rate was 61 % (32/52). However, as only inoperable patients with advanced tumors were treated in this pilot study, the survival time is rather short for most patients. Only 8 patients are alive at the time of writing. The results of treatment for inoperable malignancies of the major salivary glands are very promising, as initial complete regression was achieved in over 90% (12/13).

RBE values of 15 MeV neutrons for responses of pulmonary metastases in patients

Abstract Pulmonary metastases in 13 patients have been irradiated with single doses of 15 MeV neutrons or 60 Co gamma rays. Volume changes were measured from chest radiographs. In patients with multiple metastases, doses of neutrons and gamma rays were applied to different metastases. In patients with metastases in one lung only, the response to neutrons was evaluated first and gamma rays were given after the metastases had regrown to the pre-irradiation volume. From the measured volume changes for different types of tumours, the effectiveness of both radiations was evaluated and RBE values of 15 MeV neutrons were derived. RBE values ranged from 1·2 to 4·0 and showed a correlation with the growth rate of the lung metastases. These data indicate that 15 MeV neutrons could provide an advantage for slowly growing tumours.

Fast neutron therapy for locally advanced sarcomas

Abstract In this paper preliminary results of 22 patients irradiated with d + T fast neutrons for advanced sarcomas are described. The results were disappointing as only 8 patients achieved local tumor control and 6 patients had severe radiation damage. These results are compared with data described by other authors.

POSSIBLE CLINICAL MODELS FOR QUANTITATIVE COMPARISON OF EFFECTS OF DIFFERENT RADIATIONS ON TUMOURS.

Abstract It cannot be expected that the use of fast neutrons instead of conventional radiation, will cause large improvements in cure rate of human tumours. Therefore controlled clinical trials of different types of tumours, requiring many years of observation will be necessary to assess possible gains. In addition to values from experiments with animal tumours, there is a need for clinical models which can provide quantitative data on the direct effects and on the RBE of fast neutrons in human tumours. The possibilities and properties of some of these models are discussed. Pulmonary metastases presumably offer the best possibilities for a comparative study of effects of photons and fast neutrons.

Present state and prospects of fast particle therapy in Europe

Abstract Apart from the Hammersmiths group in London, clinical experience with fast neutrons is still very limited in Europe. Since 1972 a periodically available beam from a cyclotron in Dresden was used for treating patients by Prof. Elebborn in Berlin (G.D.R.), in which about one third of the total dose was applied by means of neutrons. In this combination a favourable effect of the addition of neutrons was seen. Efforts to construct a neutron machine for clinical use in the hospital, resulted in the installation of D-T generators in Manchester, Glasgow, Amsterdam and Hamburg. Treatment of patients started in Amsterdam in August 1973 and in Hamburg early this year. Recently a D-T generator has been installed for this purpose in Heidelberg. Clinical application of fast neutron beams from cyclotrons will be effected during the next year in Louvain (Belgium), Essen (F.D.R.) and Edinburgh (U.K.). In a couple of years pi-mesons from a synchrotron near Zurich and heavy ions from a synchrotron in France probably will become available for therapeutic studies. A European Study Group will try to coordinate the efforts in the various centers. More detailed information is now described with regard to clinical experience up to now and the planning for the future in various centers.

International cooperation with regard to clinical trials of fast neutron radiotherapy

Abstract A review is presented of various problems which require international cooperation between radiotherapy centres in order to derive insight into the value of fast neutron radiotherapy within the shortest time and with the smallest expenditure of money and effort possible.