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Title: Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma

Abstract

Purpose: To determine the radiobiologic parameters for high-grade gliomas. Methods and Materials: 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 (SF{sub 2}) data, and the above {alpha}/{beta} ratio, the estimated median {alpha} value was 0.077 Gy{sup -1}, {beta} was 0.009 Gy{sup -2}, and the cellular doubling time was 39.5 days. The median equivalent biologic effective dose of temozolomide was 11.03 Gy{sub 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 tumormore » control, which are further supplemented by temozolomide, are achievable. Conclusion: 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.« less

Authors:
 [1];  [2]
  1. Birmingham Cancer Centre, University Hospital Birmingham, Birmingham (United Kingdom). E-mail: b.jones.1@bham.ac.uk
  2. Birmingham Cancer Centre, University Hospital Birmingham, Birmingham (United Kingdom)
Publication Date:
OSTI Identifier:
20951663
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.12.025; PII: S0360-3016(06)03650-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; CLINICAL TRIALS; DOSE EQUIVALENTS; FRACTIONATED IRRADIATION; GLIOMAS; PATIENTS; RADIATION DOSES; RADIOBIOLOGY; RADIOSENSITIZERS; RADIOTHERAPY

Citation Formats

Jones, Bleddyn, and Sanghera, Paul. Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.025.
Jones, Bleddyn, & Sanghera, Paul. Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma. United States. doi:10.1016/j.ijrobp.2006.12.025.
Jones, Bleddyn, and Sanghera, Paul. Fri . "Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma". United States. doi:10.1016/j.ijrobp.2006.12.025.
@article{osti_20951663,
title = {Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma},
author = {Jones, Bleddyn and Sanghera, Paul},
abstractNote = {Purpose: To determine the radiobiologic parameters for high-grade gliomas. Methods and Materials: 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 (SF{sub 2}) data, and the above {alpha}/{beta} ratio, the estimated median {alpha} value was 0.077 Gy{sup -1}, {beta} was 0.009 Gy{sup -2}, and the cellular doubling time was 39.5 days. The median equivalent biologic effective dose of temozolomide was 11.03 Gy{sub 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. Conclusion: 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.},
doi = {10.1016/j.ijrobp.2006.12.025},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}
  • Purpose: To estimate a plausible set of radiobiologic parameters such as {alpha}, {alpha}/{beta} values, from clinical outcomes for biologically based radiation treatment planning of brain tumors. Methods and Materials: Linear-quadratic (LQ) formalism and the concept of equivalent uniform dose were used to analyze a series of published clinical data for malignant gliomas involving different forms of radiation therapy. Results: A plausible set of LQ parameters was obtained for gliomas: {alpha} = 0.06 {+-} 0.05 Gy{sup -1}, {alpha}/{beta} = 10.0 {+-} 15.1 Gy, the tumor cell doubling time T{sub d} = 50 {+-} 30 days, with the repair half-time of 0.5more » h. The present estimated biologic parameters can reasonably predict the effectiveness of most of the recently reported clinical results employing either single or combined radiation therapy modalities. Different LQ parameters between Grade 3 and Grade 4 astrocytomas were found, implying the radiosensitivity for different grade tumors may be different. Smaller {alpha}, {beta} from in vivo was observed, indicating lower radiosensitivity occurred in vivo as compared with in vitro. Conclusions: A plausible set of radiobiologic parameters for gliomas was estimated based on clinical data. These parameters can reasonably predict most of the clinical results. They may be used to design new treatment fractionation schemes and to evaluate and optimize treatment plans.« less
  • Purpose: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. Methods and Materials: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. Results: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of thosemore » with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Conclusion: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively.« less
  • The size of the thyroid glands was analyzed for 10% of the patients in a selected group that had been exposed to diagnostic doses of /sup 131/I. The mean thyroid gland weight +- SD was 50 +- 33 g for patients 20 or more years of age and 10 +- 5 g for patients less than 20 years of age. With the present follow-up, diagnostic doses of /sup 131/I appeared not to be associated with an increased risk for later development of malignant thyroid tumors. Possible reasons for the difference between the observed number of such tumors and the numbermore » expected (47 to 124) on the basis of risk estimates of the United Nations Scientific Committee on the Effects of Atomic Radiation are discussed.« less
  • Purpose: Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional dose distributions for each individual patient. These data open up new possibilities for more precise estimates of secondary cancer incidence rates in the irradiated organs. We report a new method to estimate organ-specific radiation-induced cancer incidence rates. The concept of an organ equivalent dose (OED) for radiation-induced cancer assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer incidence. Methods and Materials: The two operational parameters of the OEDmore » concept are the organ-specific cancer incidence rate at low doses, which is taken from the data of the atomic bomb survivors, and cell sterilization at higher doses. The effect of cell sterilization in various organs was estimated by analyzing the secondary cancer incidence data of patients with Hodgkin's disease who were treated with radiotherapy in between 1962 and 1993. The radiotherapy plans used at the time the patients had been treated were reconstructed on a fully segmented whole body CT scan. The dose distributions were calculated in individual organs for which cancer incidence data were available. The model parameter that described cell sterilization was obtained by analyzing the dose and cancer incidence rates for the individual organs. Results: We found organ-specific cell radiosensitivities that varied from 0.017 for the mouth and pharynx up to 1.592 for the bladder. Using the two model parameters (organ-specific cancer incidence rate and the parameter characterizing cell sterilization), the OED concept can be applied to any three-dimensional dose distribution to analyze cancer incidence. Conclusion: We believe that the concept of OED presented in this investigation represents a first step in assessing the potential risk of secondary cancer induction after the clinical application of radiotherapy.« less
  • Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell killmore » as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.« less