Irradiation of the microvasculature with fast neutrons.

Single- and split-dose irradiation of the eyes of dogs was performed with cyclotron-produced polyenergetic neutrons at a rate of about 0.2 Gy (20 rad) per minute. Neovascularization was subsequently induced surgically in the avascular corneas and stimulated for 7 days to study the response of slowly proliferating capillary endothelial cells. Corneal tissue samples were evaluated quantitatively by morphometric methods. A dose-response curve was drawn by plotting per cent capillary volume versus dose. D0 was 2 Gy (200 rad), and the recovery ability was determined to be equivalent to 1.3 Gy (130 rad). Depending on the level of damage, relative biological effectiveness (RBE) values were 1.9 to 2.3.     

Clinical experience with fast neutrons in Amsterdam.

Since November 1972 a pilot study of fast neutron therapy has been carried out in Amsterdam at the Antoni van Leeuwenhoek Hospital (the Netherlands Cancer Institute). With a d + T machine almost 200 patients were treated in 2 years. In this paper the preliminary results will be discussed.     

How to draw irregular radiation beams in 3-D treatment plans

We describe a general method for computing the outline which an irregular field originating from some arbitrary angle makes on a plane which may be oriented obliquely within the patient. We describe the mathematical theory of the method, which is based on coordinate transformations expressed as matrix multiplications. Then we describe the implementation of the method in the Pascal programming language, emphasizing language-independent optimizations which ensure fast interactive response. Finally, we describe a systematic program testing procedure that is derived from the mathematical theory, which improves our confidence that the method is coded correctly.     

Chemical composition identification using fast neutrons.

Measurements of characteristic gamma ray spectra resulting from A(n, n'gamma)A reactions induced by 14 eV neutrons on different bulk samples (graphite, water, melamin) were performed. Of particular importance are results of experiments with objects buried in the soil. It has been shown that samples of graphite can be identified when buried under 10 m of soil. NaI(Tl) and BaF(2) scintilators were used as gamma ray detectors. Background radiation was reduced by the associated alpha particle technique.     

Radiography and tomography with fast neutrons at the FRM-II--a status report.

For the basic instrumentation of the new research reactor FRM-II, Munich, a radiography/tomography facility using fast neutrons is under construction. The main features of the facility and results of simulation studies on characteristic parameters are presented.     

The role of fast neutrons in radiooncology--a critical appraisal.

The contribution of fast neutrons to local tumour control has been investigated worldwide since the mid-60's in more than 20 institutions. The high expectations anticipated from the promising results of experimental studies could not be adequately realized in the clinic. The late normal tissue damage was unacceptable due to poor depth dose characteristics and further technical limitations of the first generation low-energy machines. Even with sophisticated therapy planning systems and high-energy cyclotrons as well as comparable late normal tissue damage as witnessed after photons, only a few tumour entities have responded superiorly to fast neutrons. These particularly include macroscopic tumours of the salivary glands, prostate and, potentially, soft and osseous tissues. The role of fast neutrons for head and neck cancer has not yet been definitely proved. For bladder-, cervical- and rectal carcinomas, non-small cell lung-, pancreatic- and breast cancers as well as malignant gliomas, no therapeutic benefit as compared with photons was observed in the case of macroscopic residual or inoperable recurrent tumours.     

The generation of fast neutrons in a cyclotron using helium-3 ions

In order to use the fast neutron flux of a cyclotron for applied purposes, the energy spectrum of the fast neutrons produced during the irradiation of a thick beryllium target with 32 MeV helium-3 ions was measured. The spectrum of the neutrons with an energy of 0.5 MeV < E_n < 17 MeV was measured at the angle 0 = 0° using a scintillation spectrometer with a stilbene crystal. The absolute neutron flux with an energy of E_n > 0.05 MeV, in the spatial angle 1 steradian, was measured by activation using In and Al detectors and was found to be 1.2 × 10⁹n/μA·sec. The neutron yields produced by irradiating a beryllium target with deuterons, α-particles and helium-3 ions are compared.     

CT-image-based conformal brachytherapy of breast cancer. The significance of semi-3-D and 3-D treatment planning.

PURPOSE: To compare the conventional 2-D, the simulator-guided semi-3-D and the recently developed CT-guided 3-D brachytherapy treatment planning in the interstitial radiotherapy of breast cancer. PATIENTS AND METHODS: In 103 patients with T1-2, N0-1 breast cancer the tumor bed was clipped during breast conserving surgery. Fifty-two of them received boost brachytherapy after 46 to 50 Gy teletherapy and 51 patients were treated with brachytherapy alone via flexible implant tubes. Single, double and triple plane implant was used in 6, 89 and 8 cases, respectively. The dose of boost brachytherapy and sole brachytherapy prescribed to dose reference points was 3 times 4.75 Gy and 7 times 5.2 Gy, respectively. The positions of dose reference points varied according to the level (2-D, semi-3-D and 3-D) of treatment planning performed. The treatment planning was based on the 3-D reconstruction of the surgical clips, implant tubes and skin points. In all cases the implantations were planned with a semi-3-D technique aided by simulator. In 10 cases a recently developed CT-guided 3-D planning system was used. The semi-3-D and 3-D treatment plans were compared to hypothetical 2-D plans using dose-volume histograms and dose non-uniformity ratios. The values of mean central dose, mean skin dose, minimal clip dose, proportion of underdosaged clips and mean target surface dose were evaluated. The accuracy of tumor bed localization and the conformity of planning target volume and treated volume were also analyzed in each technique. RESULTS: With the help of conformal semi-3-D and 3-D brachytherapy planning we could define reference dose points, active source positions and dwell times individually. This technique decreased the mean skin dose with 22.2% and reduced the possibility of geographical miss. We could achieve the best conformity between the planning target volume and the treated volume with the CT-image based 3-D treatment planning, at the cost of worse dose homogeneity. The mean treated volume was reduced by 25.1% with semi-3-D planning, however, it was increased by 16.2% with 3-D planning, compared to the 2-D planning. CONCLUSION: The application of clips into the tumor bed and the conformal (semi-3-D and 3-D) planning help to avoid geographical miss. CT is suitable for 3-D brachytherapy planning. Better local control with less side effects might be achieved with these new techniques. Conformal 3-D brachytherapy calls for new treatment planning concepts, taking the irregular 3-D shape of the target volume into account. The routine clinical application of image-based 3-D brachytherapy is a real aim in the very close future.     

Clinical results with fast neutrons (DT, 14 MeV)

In Hamburg, the therapy with DT-neutrons had the best curative effect on highly differentiated tumors. With the standard dose of 15.6 Gy in four weeks with fast neutrons only or--in treating tumors in radiosensitive organs such as brain and intestine--with a photon-neutron schedule, we have seen no necroses in normal tissues. The rate of medium or slight subcutaneous fibroses has been no 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 rectal 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 DT-neutrons is higher than with cyclotron-produced neutrons.     

Metal ions protect DNA against strand breakage induced by fast neutrons.

Single and double strand breaks (SSB and DSB) are induced by fast neutrons in plasmid (pBR322) DNA in 1 mM potassium phosphate buffer (pH 7.25). Increasing the concentration of monovalent (Na+, Cs+, Li+), divalent (Mg2+, Ca2+) and trivalent (Al3+, Co3+ (NH3)6) metal cations strongly decreases the yield of DSB. The extent of the observed protection depends on the valence of the cation. The production of SSB is only slightly decreased, except for Al3+ and Co3+ (NH3)6, whose effects are particularly large (complete protection at 1 and 0.1 mM respectively). Circular dichroism spectra show that Al3+ induces an important structural change of DNA at the ion concentration where the protection becomes total. This change is probably a condensation (collapse), as in the well-known case of Co3+ (NH3)6. Our results suggest two mechanisms of protection by metal ions: (i) the induction of structural changes of DNA, that render less accessible the critical sites of attack by OH. radicals; and (ii) the stabilization of the double helical regions between two close-set nicks on opposite strands, that hinders the effective double strand breakage of DNA.