Scenario:
     Since the first observation on the induction of chromosome aberrations in blood lymphocytes of patients received radiotherapy by I. M. Tough, K. E. Buckton, A. G. Baikie and W. M. Court Brown in 1960 (Tough et al., Lancet, ii:849-851, 1960), lymphocyte chromosome aberration analysis rapidly expanded in varying area of radiation cytogenetics of humans exposed to ionizing radiation. Chromosome aberration analysis provides not only a quantitative measure of the biological effects of radiation in humans (IAEA Technical Report 2011; ISCN 2016) but also an important information in establishing correct clinical management in radiotherapy and radiation accident. Currently, estimation of dage to lymphocytes during radiotherapy is made basing on the overall frequencies of chriomosome aberrations leading to equivalet hole-bady dose. However, there is a limitation in the use of such simple inference to in vitro dose-response curves because the doses are not homogeneous. Here, we attempt an alternative biodosimetry system, as refered to as "unforlding method", in which distribution of chromosome aberrations are decomboluted into dose distribution profiles (Sasaki, M. S. (2003): Int. J. Radiat. Biol., 79:83-97). The unfolding of aberration distribution into dose distribution was tested in radiotherapy for various degrees of dose homogeneity, loalized exposure (location and field size) and/or inhomegeneous hit to cells by heigh LET charged perticle. The information may be useful to the biological dosimetry in general, because the dose is usually inhomogeneous in radiation exposure in humans, in spatial as well as celluar aspect.

Commentary:
     Currently, whole body dose during radiotherapy has been estimated by direct comparison of aberration frequencies to the in vitro dose-response curve. The reference dose-response curve adopted is usually constructed based on linear-quadratic model. However, this model can only be applied to doses below 3-5 Gy-E. Above this dose limit, the dose-response starts to to be bent, and hence the interporated dose tend to be under estimated. To cope with this difficulty, more generalized dose-response curve available for doses up to 50 Gy has been proposed (Sasaki, Int. J. Radiat. Biol., 79:83-97, 2003). The model enable direct inference to doses up to 50 Gy ("direct inference") and also reconstruct dose distribution profile by decombolution of aberration distribution ("unfolding"). The former have been applied to the chromosome aberration analysis in literature (the last column of the table). However, this method does not include the modification of aberration frequencies by cell killing. The latter method provides equivalent whole body dose (EWBD) and dose distribution either with or without adjustment by cell killing. The dose distribution profiles after adjustment are presented at the end of chromosome aberration data. The adjustment was made by lymphocyte survival, S=D/D₀, in which D₀=3 Gy (Edwards et al., Int. J. Radiat. Biol., 38:83-91, 1980).

(a) Patient with Hodgkin lymphoma treated with 15 MeV X-rays.

Reference
     Diener, A., Stephan, G., Vogl, Th. and Lissner, J. (1988): The induction of chromosome aberrations during the course of radiation therapy for Morbus Hodgkin. Radiat. Res., 114:528-536.

No. of Dose to tumor Cells Distribution of cells with indicated number of dicentrics Chromosomally estimated dose, Gy-E fraction (Gy) scored 0 1 2 3 4 5 6 7 8 10 Ave (95% CI) 1 1.8 1,001 949 42 10 0.846 (0.664, 1.065) 3 5.4 613 492 91 24 5 1.907 (1.625, 2.244) 6 10.8 604 433 116 45 9 1 2.490 (2.168, 2.879) 10 18.0 200 116 44 18 10 4 2 1 3.574 (3.081, 4.156) 12 21.6 200 89 58 21 17 6 1 1 1 4.240 (3.702, 4.880) 21 37.8 400 221 65 54 26 7 4 4 3 1 1 4.075 (3.621, 4.623)

(b) Relatively large irradiation field: Breast cancer patients (9 patients) treated with ⁶⁰Co gamma-rays.

Reference
     Rigaud, O., Guedeney, G., Duranton, I., Leroy, A., Doloy, M. T. and Magdelenat, H. (1990): Genetoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. I. Chromosome aberrations induced in vivo. Mutation Res., 242:17-23.

(c) Relatively small irradiation field: Cervical cancer patients (29 patients) treated with ⁶⁰Co gamma-rays.

Reference
     Venkatachalam, P., Paul Solomon, F. D., Karthikeya Prabhu, B., Monhankumar, M. N., Gajendiran, N. and Jeevanram, R. K. (1999): Estimation of dose in cancer patients treated with fractionated radiotherapy using translocation, dicentrics and micronuclei frequency in peripheral blood lymphocytes. Mutation Res., 429:1-12.

(4) Relatively localized irradiation field: Cervical cancer patients (8 patients) treated with carbon ion beams (350-400 MeV) at HIMAC. Treatment consisted of a fixed total number of fractions and treatment time of 24 fractions over 6 weeks with 4 fractions per week. The treatment covered cervical tumor and pelvis lymph nodes. The initial fraction was 2.2 Gy-E, which was followed by progressive increase of dose per fraction, giving a total dose of 52.8 Gy-E to 72.8 Gy-E (see, Nakano et al. Clin. Cancer Res., 12:2185-2190, 2006).

Reference
Unpublished data. Data scored by I. Hayata (National Institute of Radiological Sciences, Chiba) and M. S. Sasaki (Radiation Biology Center, Kyoto University, Kyoto).