Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models.

We examined the effect of radiotherapy after hyperbaric oxygen (HBO) breathing in experimental tumors using a tumor growth delay assay. Tumor models used were SCCVII (radiobiological hypoxic fraction: approximately 10%) and 9L tumors (containing less hypoxic cells) subcutaneously transplanted into C3H/He mice and Fisher 344 rats, respectively. Irradiation using X-rays was locally administered to the tumors immediately after decompression. HBO breathing enhanced the radiation response in SCCVII tumors but not in 9L ones. In the next experiment using SCCVII tumors, irradiation was administered 5, 15, 30, and 90 min after decompression. A significant growth delay was seen in the treated animals within 30 min after HBO breathing, and the tumor growth delay time was prolonged 1.61 times as long as that in radiotherapy alone. We concluded that: (1) radiotherapy after HBO breathing is effective for tumors with hypoxic cells; and (2) the time lapse from decompression to irradiation is an important factor in improving radiosensitivity. Radiotherapy after HBO breathing can be used to enhance the efficacy of clinical treatments.

Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging.

Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the dissolved molecular oxygen in tissue. Using a non-invasive magnetic resonance imaging (MRI) technique, we monitored the changes in MRI signal intensity after HBO exposure because dissolved paramagnetic molecular oxygen itself shortens the T1 relation time. SCCVII tumour cells transplanted in mice were used. The molecular oxygen-enhanced MR images were acquired using an inversion recovery-preparation fast low angle shot (IR-FLASH) sequence sensitizing the paramagnetic effects of molecular oxygen using a 4.7 tesla MR system. MR signal of muscles decreased rapidly and returned to the control level within 40 min after decompression, whereas that of tumours decreased gradually and remained at a high level 60 min after HBO exposure. In contrast, the signal from the tumours in the normobaric oxygen group showed no significant change. Our data suggested that MR signal changes of tumours and muscles represent an alternation of extravascular oxygenation. The preserving tumour oxygen concentration after HBO exposure may be important regarding adjuvant therapy for cancer patients.

Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas.

The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression.

Modification of radio-thermo-chemotherapy by AK-2123 and hydralazine in tumor bearing mice.

The effects of chemical modifiers of hypoxic radiosensitizer, a 3-nitrotriazole derivative AK-2123 (200 mg/kg) before treatment, and vasodilator of hydralazine (HDZ; 5.0 mg/kg) after treatment on tumor growth of SCCVII of mice were investigated in the radio-thermotherapy combined with mitomycin C (MMC; 2.0 mg/kg) or adriamycin (ADM; 3 mg/kg). The tumor treated by 10 Gy alone (tumor doubling time = 7.5 days), MMC alone (6.9 days), and hyperthermia (43 degrees C, 30 min; HT) alone (8.0 days) showed a slight growth delay (control: 5.6 days). Prolonged growth delay (23.2 days) was observed by MMC-radio-thermotherapy (MMC-10Gy/HT) than that (12.4 days) by 10 Gy/HT. The modification of MMC-radio-thermotherapy by HDZ administered between 10 Gy and HT (MMC-10 Gy/HDZ/HT) resulted in the significant prolongation of tumor growth delay (31.7 days). AK-2123 administration before this treatment, (MMC-AK-2123)-10 Gy/HDZ/HT), enhanced a further tumor growth delay (37.6 days) which is equal to that by 50 Gy alone and resulted in the highest dose modifying factor (DMF) of 5.2. While modification of ADM-radio-thermotherapy by AK-2123 and HDZ, (ADM-AK-2123)-10 Gy/HDZ/HT, gave the equal tumor growth delay to that by 30 Gy alone (DMF = 3.1). These high efficacies of radio-thermo-chemotherapy modified by AK-2123 and HDZ may be caused by tumor blood flow reduction.

[Combined radiotherapy and hyperthermia for Pancoast tumor].

Thirteen patients with Pancoast tumor were treated with combined radiotherapy and hyperthermia from April 1987 to December 1992. Radiotherapy was performed using 10 MV X-rays, and all patients received a total dosage of 40-118 Gy with conventional fractionation. Hyperthermia was performed once or twice a week within 30 minutes after each irradiation, using 8 MHz RF capacitive heating equipment (Thermotron RF-8). Partial response, defined as 50% or more regression of the tumor, was observed in 7/13 (54%) patients, and the median survival time was 25.2 months. Results of 14 patients treated with irradiation alone from July 1980 to December 1992 were also evaluated, and were used as a historical control. The partial response was 4/14 (29%) and the median survival time was 7.3 months. Radiotherapy combined with hyperthermia is an effective modality for treating Pancoast tumors.

[Thermal distribution in the agar phantom by a new intracavitary RF applicator for prostate gland].

Some studies suggest that the prostate gland is one of the most difficult portions of the body to heat up even by radio frequency (RF) capacitive heating, which is well established as a useful means for deep regional hyperthermia because of its non-uniform power absorption. We have developed a new type of intracavitary applicator for RF capacitive heating which can be connected to an 8 MHz RF heating device (Thermotron-RF8). The applicator is a balloon-type catheter which is filled with electrolyte, such as physiological saline, 3% saline or 3% ferrous sulfate solution, and then put between a pair of regular RF capacitive heating electrodes. The heating characteristics of the applicator were examined by using an agar phantom that is electrically equivalent to muscles. When the applicator was connected to the electrode of the RF generator with a copper cord, the balloon filled with electrolyte operated as an inner electrode. The effective hot area around the balloon of the catheter was observed, and the size of the hot area was changed by the kinds of electrolytes used and their concentration. With this adaptive technique, it is possible to maintain an adequate thermal distribution at a tumor in the uterus, urinary bladder and rectum, as well as the prostate gland.

Pancoast tumour treated with combined radiotherapy and hyperthermia--a preliminary study.

Six patients with Pancoast (superior sulcus) tumours were treated with combined radiotherapy and hyperthermia from April 1986 to December 1989. Radiotherapy was performed using 10 MV X-ray, and all patients received total doses of 60-74 Gy, in five fractions per week, during 5.5-15 weeks. Hyperthermia was performed once or twice a week within 30 min after each irradiation, using 8 MHz RF capacitive heating equipment (Thermotron RF-8). Partial response, defined as 50% or more regression of the tumour, was observed in four of the six patients. Three patients are alive 30, 28, and 14 months after their treatments. Radiotherapy combined with hyperthermia appears to be a promising and effective means for treating Pancoast tumours.

Biological assessment of the enhancement of tritium excretion by administration of diuretics and excessive water in mice.

This study was undertaken to determine whether or not the administration of diuretics and excess water after tritium exposure would have any positive reducing effect not only on the retention of tritium but also on the radiation damage of hematopoietic tissue in mice. When mice were treated with diuretics and excess water for a few days after injection of tritiated water (HTO), radioactivity within the body fluid and tissues was reduced, and the number of CFU-s, clonability of splenic T cells and proliferative activity assayed by Con-A blastogenesis were increased in comparison with those in the controls. When the mice were injected with a large dose of HTO (811 MBq/mouse) to assay survival, no mice treated with diuretic and excess water died 80 days after injection, while 80% of the controls died during the first month. The final committed dose in the mice treated early with diuretics was calculated to be 60% of that in the controls. These results suggest that treatment with diuretics and excess water is useful for practical purposes when a human is accidentally exposed to tritium.