Response of the Rat Dunning R3327-AT1 Prostate Tumor to Treatment with Fractionated Fast Neutrons

Abstract

Reports indicate that cancer of the prostate, soft tissue sarcomas, salivary gland tumors, and melanomas respond well to fast-neutron treatment. To better understand the action of fast neutrons on such tumor tissues, we have begun studies with the versatile Dunning rat prostate tumor system. In our initial studies with the R3327-AT1 subline we observed a relative biological effectiveness (RBE) of approximately 3 for single doses of 14-meV fast neutrons. As a continuation of those studies the present report discusses our findings following fractionated treatments with 10 equal fractions of 14-MeV fast neutrons or 60Co gamma rays at several dose levels per fraction. After either fractionated neutron or photon treatment the volume of the tumors continued to increase for 2 weeks and then reached a plateau, the level of which was dose dependent. Tumor growth resumed and no local control was observed. Analysis of the data using growth delay as biological end point yielded an RBE of approximately 4.2 +/- 1.3.

Differential effects of CLDR and PDR brachytherapy on cell cycle progression in a syngeneic rat prostate tumour model

“…A previous study revealed a statistically significant reduced efficacy (tumour growth delay) of PDR compared to CLDR treatment after application of 20 Gy and 30 Gy, respectively (Harms et al 2002a), whereas no such difference was found for a dose range of 40 -50 Gy. Given the presumed equivalence of these treatments modalities with respect to sublethal damage recovery phenomenon (Brenner & Hall 1991, Fowler & Mount 1992) and, even more, the only modest sensitivity of this tumour model towards changes in fractionation (Peschke et al 1992(Peschke et al , 1998, have led to the postulation of possible differential effects on cell cycle progression of a continuous versus a pulsed irradiation schedule (Harms et al 2002b). This was tested in the present investigation.…”

“…The volume doubling time is 2.7 days up to tumour volumes of 500 mm 3 which then increases to 5.2 -5.6 days (Isaacs & Coffey 1983, Lohr et al 1993. Earlier studies revealed only a modest sensitivity of the AT1 subline to changes in fractionation suggesting a high a/b ratio (Peschke et al 1992(Peschke et al , 1998.…”

Assessment of tumor response to oxygen challenge using quantitative diffusion MRI in an animal model

“…This study was approved by the Institutional Animal Care and Use Committee. A well-characterized Dunning R3327-AT1 rat prostate cancer line 24,25 was implanted subcutaneously via a small incision in the right thigh of male Copenhagen rats ($270 g, Charles River, TX), as described in detail previously. 26 MRI was performed when tumors reached approximately 1.5-2 cm in diameter.…”

“…Materials and Methods: A well-characterized Dunning R3327-AT1 rat prostate cancer line was implanted subcutaneously in the right thigh of male Copenhagen rats (n 5 8). Diffusion-weighted images (DWI) with multiple b values (0,25, 50, 100, 150, 200, 300, 500, 1000, 1500 s/mm 2 ) in three orthogonal directions were obtained using a multishot FSEbased Stejskal-Tanner DWI sequence (FSE-DWI) at 4.7T, while rats breathed medical air (21% oxygen) and with 100% oxygen challenge. Stretched-exponential and intravoxel incoherent motion (IVIM) models were used to calculate and compare quantitative diffusion parameters: diffusion heterogeneity index (a), intravoxel distribution of diffusion coefficients (DDC), tissue diffusivity (Dt), pseudo-diffusivity (Dp), and perfusion fraction (f) on a voxel-by-voxel basis.…”

Changes in RBE of 14-MeV (d+T) neutrons for V79 cells irradiated in air and in a phantom: Is RBE enhanced near the surface?

“…Dunning R3327-AT1 prostatic tumors in Copenhagen rats was approximately 3 for single doses in the range 6-10 Gy and 4.2_+ 1.3 for fractionated irradiation with 1.2-1.5 Gy/fraction [14,31]. For late-reacting normal tissues with c~/[3 ratios for photons in the range of 2 to 4 [11,36], the dependence of RBE on dose per fraction would be expected to be even more pronounced.…”