The role of CD95 and CD95 ligand in cancer.

CD95 (Fas/APO-1) and its ligand, CD95L, have long been viewed as a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. In addition, these molecules are important in the immune elimination of virus-infected cells and cancer cells. CD95L was, therefore, considered to be useful for cancer therapy. However, major side effects have precluded its systemic use. During the last 10 years, it has been recognized that CD95 and CD95L have multiple cancer-relevant nonapoptotic and tumor-promoting activities. CD95 and CD95L were discovered to be critical survival factors for cancer cells, and were found to protect and promote cancer stem cells. We now discuss five different ways in which inhibiting or eliminating CD95L, rather than augmenting, may be beneficial for cancer therapy alone or in combination with standard chemotherapy or immune therapy.

A comparison of two planning techniques for radiotherapy of high grade astrocytomas.

The purpose of this study was to compare two planning techniques for the delivery of radical localized postoperative radiotherapy in the treatment of high grade astrocytomas. Conventional orthogonal plain film planning (CONP) was compared with CT planning (CTP) in terms of the size of the target volumes treated, the amount of normal brain irradiated and the accuracy of localization. Twenty consecutive adults with high grade astrocytomas, who were treated with radiotherapy between March and October 1996, were planned with CONP and CTP, using postoperative, contrast-enhanced CT scans to define the tumour volume. The planning target areas, volumes and the 100%, 80% and 50% isodose areas produced using the two planning methods were measured and compared using Student's paired t-test. The target volume length was also measured and compared as an independent factor. The difference between entry points of the central axis of the lateral fields was noted. Nineteen of 20 patients had a reduction in planning target volumes using CTP compared with CONP. The difference between the mean volumes was clinically relevant, with 288 cm3 representing a 25% reduction, and statistically significant at the P<0.001 level. The planning target volumes were reduced in 18/20 patients (mean 24 cm2, 23%, P<0.001). Similarly, there were highly significant reductions in the 100%, 80% and 50% isodose areas. The target volume lengths were not found to be significantly different. When considering the accuracy of localization, the entry point of the CONP lateral field deviated by a mean distance of 1.6 cm relative to CTP (superiorinferior 1.3 cm; anteriorposterior 0.8 cm; range 04.1 cm). In two patients, this would have led to a geographical miss of macroscopic disease. In patients with high grade astrocytomas, CTP is preferred to conventional planning. It leads to appreciable reductions in the size of the planning target areas and volumes receiving radical doses of radiation, it significantly reduces the amount of normal brain tissue being irradiated and is more accurate in terms of tumour localization. These differences are likely to lead to a reduction in treatment morbidity. We recommend CTP for all patients receiving radical radiotherapy.