Radiobiological basis for cancer therapy by total or half-body irradiation

Abstract

The tumor control effects by total-body irradiation (TBI) or half-body irradiation (HBI) on tumor-bearing mice and human cancer were investigated. In fundamental studies using a murine experimental system, mice that received 10 or 15 cGy of TBI showed a high value of TD(50) (number of tumor cells required for successful transplantation to a half group of injected sites) compared with nonirradiated control mice. The combination of low doses of TBI and local irradiation on tumor-bearing mice demonstrated enhanced tumor cell killing compared with only local irradiation, but this tumor-cell killing effect was not observed following 10 or 15 cGy of TBI alone. However, the suppression of distant metastasis of tumor cells was observed following low doses of TBI alone. Immunological studies on these effects suggested that TBI or HBI caused immunopotentiating effects. In clinical studies, malignant lymphoma (non-Hodgkin's lymphoma) was selected as the first disease for clinical trial. The results were promising for tumor control applications, except for advanced cases and very aged patients.

Keywords: TD50; murine squamous carcinoma; non-Hodgkin’s lymphoma; total-body irradiation; tumor immunology.

FIGURE 1

Changes of TD50 value with dose in WHT/Ht mice inoculated with epithelioma cells, 30 min after TBI (K. Sakamoto, unpublished data).

FIGURE 2

Change of TD50 value in WHT/Ht mice inoculated with epithelioma cells at different times after 10cGy of TBI (Sakamoto et al., 1987a).

FIGURE 3

Survival curves of epithelioma cells exposed to graded dose of X-rays locally to the tumor, with or without TBI of 10cGy (Sakamoto et al., 1987b): •, high-dose local irradiation; ▵, combined method of TBI and high-dose local irradiation.

FIGURE 4

Regrowth curve of tumors exposed to 35 Gy locally or to combined treatment (Miyamoto and Sakamoto, 1987): • tumors irradiated locally; ○, tumors irradiated locally, 12 h after TBI; ▴ tumors irradiated locally after five TBI treatments spaced 8 h apart; –·– nonirradiated control mice.

FIGURE 5

IL-2 response of spleen cells in tumor-bearing WHT/Ht mice. IL-2 response estimated by ³H-TdR uptake. Symbols in right corner are control values (non-tumor-bearing mice; Sakamoto et al., 1987b).

FIGURE 6

IL-2 response of spleen cells in C57 black mice bearing B16 melanoma; symbols at right-hand side are control values (Sakamoto et al., 1987b).

FIGURE 7

Change in immunoresponse of splenocytes in tumor-bearing mice (from response in non-tumor-bearing mice) without TBI and after TBI (Miyamoto and Sakamoto, 1987).

FIGURE 8

Change of phenotype of spleen cells in tumor-bearing mice caused by 10 cGy of TBI (Sakamoto et al., 1987b).

FIGURE 9

Change of phenotype of spleen cells in non-tumor-bearing mice due to 10 cGy of TBI (Sakamoto et al., 1987b).

FIGURE 10

Relative values of lung colonies in mice versus exposed dose of X-ray given 9 h before tumor-cell injection into tail vein (Hosoi and Sakamoto, 1993);p ≤ 0.05.

FIGURE 11

Effect of 15 cGy of TBI on artificial lung-colony formation: TBI given at various times before or after tumor-cell injection into tail vein (Hosoi and Sakamoto, 1993);p ≤ 0.05, ** p ≤ 0.01.

FIGURE 12

Effect of TBI dose on spontaneous lung metastasis: TBI given 12 days after tumor-cell transplantation into groin (Hosoi and Sakamoto, 1993); p ≤ 0.05.

FIGURE 13

Survival of stage I and II non-Hodgkin’s lymphoma patients treated by the combined treatment of low-dose TBI and high-dose local irradiation only (Takai et al., 1991; Sakamoto et al., 1997).

FIGURE 14

Cause-specific survival for non-Hodgkin’s lymphoma: stage I, patients treated by the combined treatment or by local irradiation only, and for stage II patients (Takai et al., 1991; Sakamoto et al., 1997).

FIGURE 15

Cause-specific survivals for histologically low-grade patients with non-Hodgkin’s lymphoma, stage I and II, treated by the combined treatment or by local irradiation only, and for intermediate, high-grade patients (Takai et al., 1991; Sakamoto et al., 1997).

FIGURE 16

Survivals of patients with non-Hodgkin’s lymphoma of stage I and II and with histologically intermediate and high-grade tumors, treated by the combined treatment or by local irradiation (Takai et al., 1991; Sakamoto et al., 1997).

FIGURE 17

Survivals of non-Hodgkin’s lymphoma patients, stage I and II, treated by the combined therapy of TBI and local irradiation compared with patients treated by the combined therapy of local irradiation followed by chemotherapy (Takai et al., 1991; Sakamoto et al., 1997); there are no significant differences in disease-free survivals between two groups.