Hyperthermia Is Now Included in the NCCN Clinical Practice Guidelines for Breast Cancer Recurrences: An Analysis of Existing Data.

BACKGROUND: Hyperthermia has been included in the 2013 National Comprehensive Cancer Network (NCCN) guidelines as an option for the treatment of breast recurrences. The purpose of this article is to demonstrate the important role of hyperthermia as a therapeutic modality by presenting clinical trials on this subject carried out in the last decades. MATERIALS AND METHODS: All relevant trials published since 1987 were retrieved from Medline and reviewed. RESULTS: Results show that the addition of hyperthermia to radiotherapy and/or chemotherapy for the treatment of breast cancer enhances treatment response and can increase local control. CONCLUSION: Further studies are required to evaluate potential benefits of hyperthermia in the treatment of other kinds of superficial tumors.

Multinational assessment of some operational costs of teletherapy.

BACKGROUND AND PURPOSE: Decisions in planning radiotherapy facilities in countries with limited financial resources require information on economic factors to make provision for sustainability. This study aims at acquiring data on some of these factors involved in delivery of teletherapy in 11 countries of different economic status. PATIENTS AND METHODS: Representatives of three European, one African, three Latin American and four Asian countries, were identified from radiation oncology institutions that operated both cobalt and linac teletherapy machines. Productivity data were prospectively collected for the year 2002. A detailed log was recorded for each machine over an arbitrary two-week period. Data on quality assurance (QA), maintenance, the capital costs of each machine, and the source replacement costs for the cobalt units were also recorded. RESULTS: Both linear accelerators and cobalt machines treat more than 10,000 fractions per year per machine with 2.5 and 2.3 fields per fraction, respectively. The capital costs of the machines vary considerably, with a factor of more than 10 for linear accelerators. Cobalt sources show a huge variation in price. The median costs of QA and maintenance of a linac was US$ 41,000 compared to US$ 6000 for cobalt machines. This results for the economic factors considered in median costs per fraction of US$ 11.02 for linear accelerators and US$ 4.87 for cobalt machines. These figures do not include the costs for physicians. CONCLUSIONS: The variation of the costs per fraction is more due to the result of differences in machine usage and costs of equipment than of national economic status. A treatment fraction on a linac with functionality comparable to cobalt, costs 50% more than cobalt therapy. This project shows that it is possible to collect data on economic factors prospectively as well as retrospectively.

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro.

Malignant gliomas are angiogenesis dependent and present a remarkable degree of resistance to radiotherapy. In the present work, we studied the effect of irradiation of C6 glioma cells on their proliferation and activation in vitro and on glioma cell-induced angiogenesis in vivo and in vitro. Irradiation of C6 glioma cells decreased cell proliferation in a dose-dependent manner. Interestingly, metalloproteinase-2 and -9 expression and secretion, as well as integrin alpha(v) expression, increased with elevated doses of X rays 48 hr after irradiation and was mostly evident at the higher doses used. When pre-irradiated C6 cells were implanted on nonirradiated chicken embryo chorioallantoic membranes (CAMs), there was a significant dose-dependent increase in tumor induced angiogenesis, compared to angiogenesis induced by nonirradiated cells. Similar results were obtained when C6 cells were irradiated 48 hr after their inoculation onto nonirradiated CAMs. In the same line, conditioned medium from irradiated C6 cells significantly increased endothelial cell proliferation and migration in vitro, in a manner dependent on the dose of X rays. These results explain at least in part the low effectiveness of radiation therapy of malignant gliomas and support the notion that inhibition of angiogenesis in parallel with radiotherapy may represent a new therapeutic approach.

Amifostine inhibits angiogenesis in vivo.

Amifostine (WR-2721) is an inorganic thiophosphate-cytoprotective agent developed to selectively protect normal tissues against the toxicity of chemotherapy and radiation. We have previously shown that amifostine protects both chicken embryo chorioallantoic membrane (CAM) vessels and cells from the effects of X-rays. In the present work, we studied the effect of amifostine on angiogenesis in vivo, using the CAM model. Amifostine decreased the number of CAM vessels in a dose-dependent manner, without being toxic for the tissue. It also decreased the mRNA levels of both vascular endothelial growth factor (VEGF) isoforms VEGF(165) and VEGF(190), 6 and up to 48 h after its application onto the CAM. Similarly, it decreased the mRNA levels of inducible nitric-oxide synthase, 24 and 48 h after drug application. Furthermore, amifostine decreased the deposited amounts of laminin and collagen I 24 h after its application, without affecting the expression of the corresponding genes. The protein amounts and activity of matrix metalloproteinase-2 were not affected, whereas the expression of the corresponding gene was decreased up to 48 h after drug application. Finally, the activity of plasmin was increased 6 h after amifostine application and remained increased at later time points. These findings suggest that amifostine alters the expression of several molecules implicated in the angiogenesis process and affects the composition of the extracellular matrix in a way that leads to inhibition of angiogenesis. Such an antiangiogenic action of amifostine, together with its radioprotective effects, further supports its use in combination with radiotherapy for increased therapeutic efficacy.

Amifostine protects blood vessels from the effects of ionizing radiation.

Amifostine (WR-2721) is a well-known radioprotective drug, selective for normal cells. The purpose of the present study was to define whether amifostine protects the vascular network from the effects of X-rays. We used the in vivo system of chicken embryo chorioallantoic membrane (CAM) as a model of angiogenesis. Amifostine reversed the early X-rays- induced decrease in the number of CAM blood vessels and reversed the early radiation-induced apoptosis of CAM cells. It also inhibited the increase in tyrosine nitration of actin and a-tubulin, which was observed 6 hours after CAM irradiation, when there was a significant decrease in non-protein SH groups. Furthermore, C6 rat glioma cells were inoculated on CAM and tumor growth, as well as tumor-induced angiogenesis, was estimated on haematoxylin-eosin-stained paraffin sections. Amifostine inhibited the post irradiation increase of C6 tumor-induced angiogenesis. These data suggest that amifostine protects CAM cells and blood vessels from the effects of X-rays, through mechanisms that do not depend solely on its free radical scavenging properties.