A Logarithmic Formula to Describe the Relationship between the Increased Radiosensitivity at Low Doses and the Survival at 2 Gray (original) (raw)
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Journal of Biomedical Physics and Engineering
Background: Establishing a predictive assay of radiosensitivity (as an appropriate, practical and cost-effective method) has been challenging. Objective: The purpose of this study is to evaluate the capability and relationship of various endpoints, including GammaH2AX, micronuclei; and apoptosis in determining the human tumor cell lines radiosensitivities compared with clonogenic survival. Material and Methods: In an experimental in-vitro study, the response of carcinoma cell lines of HN5 and HeLa to 2 Gy of 6 MV photon beam was investigated via various assays. Results: Survival fraction at 2 Gy (SF2) of HeLa and HN5 was indicated as 0.42 ± 0.06 and 0.5 ± 0.03 respectively, proposing more radioresistance of HN5. This finding was confirmed with "2 Gy apoptosis enhancement ratio" which was 1.77 and 1.42 in HeLa and HN5. The increased levels of DNA DSBs were observed after irradiation; significant in HeLa with enhancement rate of 19.24. The micronuclei formation followed an ascending trend post irradiation; but with the least difference between two cells. Although the relationship between micronuclei and clonogenic survival was moderate (R 2 = 0.35), a good correlation was observed between apoptosis and clonogenic survival (R 2 = 0.71). Conclusion: The results of studied endpoints agreed with the SF2, highlighting their capabilities in radiosensitivity prediction. In terms of the enhancement ratio, gammaH2AX foci scoring could be a valid indicator of radiosensitivity but not the exact surrogate marker of survival because no correlation was observed. Moreover, considering the chief determents comprising lack of time and money, the apoptotic induction might be an appropriate indicator with the best correlation coefficient.
International Journal of Radiation Oncology*Biology*Physics, 2003
Purpose: New insights into the kinetics of late complications occurring after radiation therapy indicated that all patients have a constant risk of developing late tissue complications. These observations might have a great impact on studies relating normal tissue complications to individual radiosensitivity. Methods and Materials: Data previously published by Peacock et al. were used for analysis. In this study, 39 breast cancer patients with severe reactions (responders) were compared with 65 matched patients showing no reactions (nonresponders). Cellular radiosensitivity as measured in vitro in terms of D 0.01 did not show significant differences between the two groups, both for high-dose-rate (5.84 ؎ 0.06 vs. 5.85 ؎ 0.07 Gy) and low-dose-rate (7.44 ؎ 0.10 vs. 7.56 ؎ 0.09 Gy) irradiation. Results: A theoretical distribution was calculated for the individual radiosensitivity of patients with Grade < 1, Grade 2, or Grade 3 reactions under the following assumptions: (1) The variation of the individual radiosensitivity is described by a normal distribution. (2) All patients and not only a subgroup have a risk of developing late complications. Based on the normal distribution of low-dose-rate data (mean value [MV] ؍ 7.56 Gy, standard deviation [SD] ؍ 0.5 Gy), a total of 200 hypothetical patients were divided into three groups: a resistant group with a sensitivity >(MV ؉ , a normal group with a sensitivity between MV ؊ SD and MV ؉ SD, and a sensitive group <(MV ؊ SD), the relative fractions being 16%, 68%, and 16%, respectively. It was assumed that these groups differed in the risk of developing late complication; for Grade 3 the annual incidence rate was set at 1%, 2%, and 4% and for Grade 2 at 5%, 10%, and 20% per year, respectively. It was shown that the mean cellular sensitivity calculated for Grade 3 (7.39 ؎ 0.10 Gy) or Grade 2 patients (7.46 ؎ 0.06 Gy) was slightly but not significantly lower than that of Grade < 1 patients (7.65 ؎ 0.04 Gy). This result demonstrated that even if the risk was assumed to depend clearly on the individual radiosensitivity, significant differences in the mean cellular sensitivity between responders and nonresponders were not expected, just as found by Peacock et al. It was shown that a significant correlation between these two parameters could be detected only when the risk was analyzed separately for each group of patients. Conclusion: Most data published so far aiming at establishing a relationship between cellular radiosensitivity and the risk of late complications might need to be reevaluated, because the questions asked up to now were inadequate to arrive at a meaningful answer.
International Journal of Radiation Biology, 2013
Purpose: To ask whether dose-rate influences low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon carcinoma PRO and REG cells. Methods: Clonogenic survival was applied to tumourigenic PRO and non-tumourigenic REG cells irradiated with 60 Co -rays at 0.0025-500 mGy.min-1. Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min-1 with 75 kV X-rays only. Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (t HRSmax and t IRRmax) were independent of dose-rate. The t HRSmax and t IRRmax values were 23±5s and 66±7s [mean±standard error of the mean (SEM), n=7), in agreement with literature data. Repair data show that t HRSmax may correspond to exposure time during which NHEJ is deficient while t IRRmax may correspond to exposure time during which NHEJ is complete. Conclusion: HRS response may be maximal if exposure times are shorter than t HRSmax irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.
International Journal of Radiation Oncology Biology Physics, 2009
Purpose: We tested whether the chromosomal radiosensitivity of in vitro irradiated lymphocytes could be used to predict the risk of acute reactions after radiotherapy. Methods and Materials: Two prospective studies were performed: study A with 51 patients included different tumor sites and study B included 87 breast cancer patients. Acute reaction was assessed using the Radiation Therapy Oncology Group score. In both studies, patients were treated with curative radiotherapy, and the mean tumor dose applied was 55 Gy (40-65) ± boost with 11 Gy (6-31) in study A and 50.4 Gy ± boost with 10 Gy in study B. Individual radiosensitivity was determined with lymphocytes irradiated in vitro with X-ray doses of either 3 or 6 Gy and scoring the number of chromosomal deletions. Results: Acute reactions displayed a typical spectrum with 57% in study A and 53% in study B showing an acute reaction of Grade 2-3. Individual radiosensitivity in both studies was characterized by a substantial variation and the fraction of patients with Grade 2-3 reaction was found to increase with increasing individual radiosensitivity measured at 6 Gy (study A, p = 0.238; study B, p = 0.023). For study B, this fraction increased with breast volume, and the impact of individual radiosensitivity on acute reaction was especially pronounced (p = 0.00025) for lower breast volume. No such clear association with acute reaction was observed when individual radiosensitivity was assessed at 3 Gy. Conclusion: Individual radiosensitivity determined at 6 Gy seems to be a good predictor for risk of acute effects after curative radiotherapy. Ó
International Journal of Radiation Oncology*Biology*Physics, 2012
This study assessed the benefit of adding a radiosensitizer to hypofractionated radiation treatment, using in-vitro clonogenic survival data. It concludes that the recently described 'generalized linear quadratic model' makes the most faithful predictions and that the additional cell kill achieved when a radiosensitzer is added to hypofractionated treatment is of a similar magnitude to that achieved when standard fractionation is used.
Overview of Radiosensitivity of Human Tumor Cells to Low-Dose-Rate Irradiation
International Journal of Radiation Oncology*Biology*Physics, 2008
We measure radiosensitivity to low-dose-rate (LDR) irradiation in 27 cell lines that vary in genotype and in radiosensitivity to high-dose-rate (HDR) irradiation. We define susceptibility to LDR-induced redistribution in the cell cycle in 15 of these cell lines.
International journal of oncology, 2013
The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction Sd/S₀ following a radiation dose d (Gy) is described by an inverse exponential approximation: Sd/S₀ = e-(αd+βd²), wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase‑1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, in...
A Short Synthesis Concerning Biological Effects and Equivalent Doses in Radiotherapys
Journal of Radiology and Oncology, 2017
It has long been known that radiation biology plays an important role and it is necessary for radiotherapy treatments. The radiation effects on normal and malignant tissues after exposure range from a femtosecond to months and years thereafter [1,2]. Therefore, to optimize treatment, it is crucial to explain and understand these mechanisms [3-5]. Providing a conceptual basis for radiotherapy and identifying the mechanisms and processes that underlie the tumor and normal tissue responses to irradiation can help to explain the observed phenomena [6]. Examples include understanding hypoxia, reoxygenation, tumor cell repopulation, or the mechanisms of repair of DNA damage [3,7,8]. The different biological effects of radiation should be divided into several phases: physical (interaction between charged particles and tissue atoms), chemical (the period during which the damaged atoms and molecules react with other cellular components in rapid chemical reactions), and biological (impact of the generated lesions on the biological tissue [4]). The following section describes the models most often used in radiotherapy. These are simplistic models that actual treatments are based, and that are validated and approved [9-12]. REFERENCE MODELS Numerous models exist to evaluate the biological equivalent dose, but the two most common are the nominal standard dose (NSD [13]) and linear quadratic (LQ [9]) models. The NSD uses the power law described in equation 1 below (D tol is the tolerance dose of the tissue, NSD is a constant, n and t , N the number of fractions, and T the overall treatment time). However, this model has been often criticized [14]. In short, some researchers consider and have even shown that the NSD formula is not a valid description for all tumors and normal tissues; instead, they maintain that the model incorrectly describes the effects of fraction number and treatment duration.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 1994
There is a wide variation in normal tissue reactions to radiotherapy and in many situations the severity of these reactions limits radiotherapy dose. Clinical fractionation studies carried out in Gothenburg have demonstrated that a large part of the spectrum of normal tissue reactions is due to differences in individual normal tissue sensitivity. If this variation in normal tissue reactions is due to differences in intrinsic cellular radiosensitivity, it should be possible to predict tissue response based on measurement of cellular sensitivity. Here we report the initial results of a study aimed at establishing whether a direct relationship exists between cellular radiosensitivity and tissue response. Ten fibroblasts strains, including four duplicates, were established from a group of patients in the Gothenburg fractionation trials who had received radiotherapy following mastectomy. Skin doses were measured and both acute and late skin changes were observed following radiotherapy. R...