**6. Our observations suggest certain studies are needed to design protocols to exploit the VR radiosensitivity phenotype observed in some glioblastoma cell lines**

Our research suggests several studies would improve selection of radiotherapy protocols that could improve therapeutic results from specific protocols.

#### **6.1 Better markers are needed to define the VR radiosensitivity phenotype from tumor biopsies**

Our studies overall suggest there is no single protocol that would be predicted to provide maximum improvement in tumor radiotherapy for all variations in the radiosensitivity phenotypes that we have observed in cells believed to be "glioblastoma" cells.

#### **6.2 The data base on the VR radiosensitivity phenotype need to be extended to include more cells presumed to be glioblastoma cells**

It seems clear from our work and that of others that a larger number of presumed glioblastoma cells need to be examined for their radiosensitivity phenotype including response to high dose-rate, to low dose-rate and their response as xenograft tumors to selected protocols.

#### **6.3 The mechanisms that underlay increased in vivo response of tumors comprised of U-251 glioblastoma cells needs to be extended to other glioblastoma cells**

Our data show this is a significant increase in radiosensitivity and the mechanisms that underlay it need to be studied in detail. The data we have presented offers a useful range of responses in different genotypes to study the role of genotype, fraction-size and total dose on this effect.
