Results of clinical applications of fast neutrons in Japan

New Radiation Oncology Optimization Principles Based On In-Vivo Predictive Assay and Recent Developments in Molecular Radiation Biology

“…In retrospect, there is actually a clinical demonstration of the value of using low-LET dose delivery in addition to high-LET treatments in the interesting US clinical trials of neutron therapy. Not only was it shown that the first ever gantry-mounted about 1m thick pure electrolytic iron multileaf collimator (to minimize neutron activation) in Seattle provided much less normal tissue damage than the ordinarily used block collimation inserts (grade 3 and 4 cumulative late normal tissue toxicity rates was reduced from 39% >10% [71]) but also the use of mixed beam treatments where a photon addition was found to be quite advantageous, as discussed in detail elsewhere [8,49,[73][74][75][76][77][78][79][80][81][82]. The above discussion was not too well understood at that time, and the results could most likely have been improved even further, as discussed here, but it is not excluded that the somewhat better dose delivery with photons may also have contributed to the improvements even if a small net survival advantage was seen with neutrons for prostate cancer [79].…”

“…Because more ions per unit dose and cell kill are needed at medium to low ionization densities, more effective apoptotic and senescent responses are obtained at ionization densities of 20 eV/ nm to 40 eV/nm, as shown theoretically and experimentally [1,2,7,39]. Interestingly, helium, lithium and beryllium combine a high local apoptotic and senescent tumor cell inactivation only a few mm around their Bragg peaks and can thus be regarded as the ultimate stereotactic, conformal and even molecular radiation therapy modalities [6,49,55,87] Interestingly, by combining lithium and boron or carbon, a uniform biological effect, survival, and absorbed dose can be obtained both for uniform tumors and with an optimal biological effect modulation for heterogeneous tumors [36,48,60,[76][77][78].…”

“…Figure 4 and [1][2][3]). The high-dose loss in cell survival is most likely due to PRIMA-1-induced augmented toxicity through the increasing associated ROS production (PRIMA-1 inhibits the enzyme thioredoxin reductase 1/Trx1 and thioredoxin and decreases cellular glutathione/GSH levels) and increasing HDA and senescence [36,48,60,[76][77][78]. The mean error!…”

Expanding Options in Radiation Oncology: Neutron Beam Therapy

“…1979) and soft tissue sarcomas (Catterall & Bewley 1979, Cohen & Awschalom 1982, Tsunemoto et al 1979). These observations suggest that it is precisely those tumour types which are resistant to conventional radiation which tend to be most responsive to high LET (linear energy transfer) radiations, in which case the availability of neutron beams could have a very significant impact on radiotherapeutic practice.…”

51. Perioperative Radiotherapie von Knochen- und Weichgewebetumoren

“…In Japan [23,25] sind mit der kombinierten Anwendung von Chemotherapie und schnellen Neutronen gute Ergebnisse erzielt worden; in Hamburg verffigen wir fiber positive Erfahrungen nur in Einzelf~illen. Diese Ergebnisse sprechen dafiir, daB bei Osteo-Sarkomen der kombinierte Einsatz von Chemotherapie, schnellen Neutronen und konservativen chirurgischen MaBnahmen zur GliedmaBenerhaltung an Bedeutung gewinnen k6nnen.…”