The Study of Connective-Tissue Reaction to Radiation. The Sieve or Chess Method

Abstract

THE focusing of attention on the malignant cell in the study of tumour tissue reactions to radiations and growth inhibitory substances has not brought us nearer the state of affairs where both practical and theoretical issues of oncology and treatment of tumours can be studied with a better understanding and fairer prospects of success. The importance of the stroma reaction to tumour and stromal reaction to radiation has been accepted for a long time, but only with generalizations on changes in "blood supply" and "tumour bed," leaving the whole problem of connective tissue reaction in a hazy state. As regards tumour tissue reaction to radiation, much stress has been laid in the past on the changes following irradiation in the cells alone, but very little attention has been paid to the intercellular tissue components. Although recent advances in cytology and genetics have enhanced the importance of the cellular nucleus, it must not be forgotten that evidence, both experimental and clinical, is available to show that the effect of ionizing radiations on cells alone "is not the whole story of the events leading to the destruction of proliferating tissues and that other factors come into play" (Muller, 1940). The great importance of connective-tissue reactions to X-rays in radiotherapeutics has been raised by Windeyer (1942), Ellis (1942), Windholz (1947). The preservation of the connective-tissue structures which contribute to repair and recovery has been taken into account in a quantitative biological control of optimal and effective dose levels in X-ray and interstitial radium therapy, and the importance of the peripheral neighbouring regions which exercise an influence on the reaction in the irradiated areas or volumes of tissues has been stressed (Jolles, 1946a, b; 1947; 1948). Conceptions of indirect action and effects on tumour cells are coming more and more to the forefront, and a clear definition of aims and avoidance of terms borrowed from radiochemistry seems of great importance. In the study of the tissue reactions to ionizing radiations several effects have to be gone into separately: (1) The direct effect of radiations on cells (intracellular effect (Koller and Smithers, 1946)). (2) The direct effect on the intercellular elements. (3) The effects on cells caused by the stroma (stromal effect). (4) The effects on cells and stroma in the irradiated tissues caused by the neighbouring tissues (external effect, Jolles).

Measurement of neutron dose equivalent outside and inside of the treatment vault of GRID therapy

“…[1][2][3][4][5] GRID therapy was initially used with orthovoltage radiation and showed its advantages in cancer treatment. 6,7 Several possible mechanisms have been proposed to explain the success of GRID therapy. 3 For patients given GRID therapy followed by conventional fractionated radiation therapy, reoxygenation is expected to improve during the subsequent conventional radiotherapy after the high local cell kills from a single, high-dose fraction.…”

Therapeutic advantage of grid irradiation for large single fractions

“…The advantages of grid use in large-dose radiotherapy (RT) have been well known since the era of orthovoltage irradiation (1,2). It was found then that when small areas of the irradiated skin and subcutaneous tissues were shielded, such as with a grid, these protected areas served as centers for regrowth of the normal tissues overlying the target.…”

Effective spatially fractionated GRID radiation treatment planning for a passive grid block

“…While the existing clinical studies 1,5 suggest improved tumour control especially for resistant tumours to conventional radiation, such as melanomas and soft tissue sarcomas, the radiobiological mechanisms of grid therapy are not fully explored. Many studies have been undertaken in order to understand the radiobiological effects of the grid treatment on tumour cells.…”

“…However, with larger tumours, especially those adjacent to critical organs, both our ability to target them and the dose that can be safely delivered could be severely compromised. The experience with megavoltage SFGRT 1,4,5 shows that the treatment mimics the dose rate pattern of high-dose brachytherapy and allows safe delivery of doses similar to stereotactic body radiation therapy (15-20 Gy, Figure 1). The technique itself has been used extensively with orthovoltage radiation until the 1970s but was not utilized with the advent of megavoltage linear accelerators.…”