Interaction of irradiation and microwave-induced hyperthermia in the Dunning R3327G prostatic adenocarcinoma model.

Abstract

The interaction of radiation and hyperthermia was systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when they had reached a volume of about 1 cm3, which occurred about 3 weeks after implantation. With the use of a randomized complete factorial design, four factors were examined. Each agent was used at one of three dose levels. For radiation, these were 5, 15, and 25 Gy; for hyperthermia, 42 degrees C for 15 minutes, 43 degrees C for 30 minutes, and 44 degrees C for 60 minutes. Two sequences (hyperthermia plus irradiation and irradiation plus hyperthermia) and five time delays between agents (0, 12, 24, 48, and 120 hours) were used. The growth delay (the time it took for the initial tumor volume to double) of subcutaneously implanted tumor served to quantitate treatment effect. Significant (P less than .05) statistical interactions were observed for several combinations of factors and individual factors. Hyperthermia plus irradiation was more effective than irradiation plus hyperthermia except at the delay time between treatments of 0 hours. Peak growth delay occurred when the time between treatments was 0-24 hours and depended on agent doses. Many combinations produced therapeutic synergy.

Heat shock protein response in a prostate tumor model to interstitial thermotherapy: Implications for clinical treatment

“…A representative heating curve illustrating the adjacent tissue temperature heated by intersitial needles vs. time is shown in Figure 1 Hours post treatment 10 12 16 24…”

The Dunning model

“…Pyrotherapy, a method which destroys tissue by heating implanted, metal-coated seeds with an external oscillating magnetic field, has also been explored as a treatment modality using this model [58,59]. Studies using the Dunning model have suggested that the combination of hyperthermia and irradiation may have an additive or synergistic effect [59][60][61]. Another form of pyrotherapy which employs high-energy ultrasound that is generated extracorporeally and focused on the target tissue has also been evaluated in this model [63][64][65].…”

“…The use of radiation in conjunction with localized hyperthermia has also been explored, as previously mentioned. Several groups have examined the synergistic effects of hyperthermia and radiation treatment, examined at several different dosages and treatment designs, and in several morphologically distinct Dunning tumors [61,62].…”

Improved therapeutic response by distinct timing of multiple heat treatments during interstitial radiation in the Dunning R3327 prostate tumor model

“…The temperature in these small s.c. tumors equilibrates within 5 min with the temperature of the waterbath. While most of the murine tumor models are rather heat-sensitive (Moorthy et al 1984;Gottlieb et al 1988;Jones et al 1989;van Geel et al 1994) the R3327-AT1 subline showed marked heat resistance. This holds not only for the application of multiple treatments (1±7 within 12 days) at 43.5°C for 35 min but also for dierent doses of heat produced by either varying the temperature applied (42.5±44.5°C) or the time (20±65 min).…”

“…The treatment modality that combines hyperthermia with radiation is one such approach and its eectiveness has been demonstrated in numerous experimental studies (Gottlieb et al 1988;Jones et al 1989;Nishimura and Urano 1993;Ryu et al 1996) as well as in several randomized clinical trials (Engin 1996;Overgaard 1989;Vernon et al 1996). The biological rationale for using such a combined modality is based on (1) a cytotoxic eect of hyperthermia, which preferentially damages acidic and nutritionally deprived cells that are considered to be hypoxic and radioresistant, and (2) on a radiosensitizing eect of hyperthermia due to its interaction with repair of radiation-induced damage.…”