Estimation of radiobiologic parameters and equivalent radiation dose of cytotoxic chemotherapy in malignant glioma.
OBJECTIVE
To determine the radiobiologic parameters for high-grade gliomas.


METHODS
The biologic effective dose concept is used to estimate the alpha/beta ratio and K (dose equivalent for tumor repopulation/d) for high-grade glioma patients treated in a randomized fractionation trial. The equivalent radiation dose of temozolomide (Temodar) chemotherapy was estimated from another randomized study. The method assumes that the radiotherapy biologic effective dose is proportional to the adjusted radiotherapy survival duration of high-grade glioma patients.


RESULTS
The median tumor alpha/beta and K estimate is 9.32 Gy and 0.23 Gy/d, respectively. Using the published surviving fraction after 2-Gy exposure (SF2) data, and the above alpha/beta ratio, the estimated median alpha value was 0.077 Gy(-1), beta was 0.009 Gy(-2), and the cellular doubling time was 39.5 days. The median equivalent biologic effective dose of temozolomide was 11.03 Gy(9.3) (equivalent to a radiation dose of 9.1 Gy given in 2-Gy fractions). Random sampling trial simulations based on a cure threshold of 70 Gy in high-grade gliomas have shown the potential increase in tumor cure with dose escalation. Partial elimination of hypoxic cells (by chemical hypoxic cell sensitizers or carbon ion therapy) has suggested that considerable gains in tumor control, which are further supplemented by temozolomide, are achievable.


CONCLUSIONS
The radiobiologic parameters for human high-grade gliomas can be estimated from clinical trials and could be used to inform future clinical trials, particularly combined modality treatments with newer forms of radiotherapy. Other incurable cancers should be studied using similar radiobiologic analysis.
Jones
Bleddyn
B
Birmingham Cancer Centre, University Hospital Birmingham, Birmingham, United Kingdom. b.jones.1@bham.ac.uk
Sanghera
Paul
P
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D009010:Monte Carlo Method; D011853:Radiobiology; D012062:Relative Biological Effectiveness; D000077204:Temozolomide; D013810:Therapeutic Equivalency
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide