Why and How does Fractionation introduces a "waste in dose", which is more pronounced for beams with a wide shoulder than for beams with a narrow shoulder in the survival curve??
It depends on the possible repair of multiple defects in subletal damaged cells for low LET radiation like gammas or betas.
In 1957, Jacobson first reported sublethal damage (SLD) in Chlamydomonas. Then, in 1959, Elkind and Sutton first reported SLD repair (SLDR) in Chinese hamster cell lines V79 and CHO. Split-dose recovery (also called Elkind recovery) has been believed to result from SLDR, although its mechanistic underpinnings remain incompletely understood.
https://www.ncbi.nlm.nih.gov/pubmed/13485385
https://www.ncbi.nlm.nih.gov/pubmed/13819951
In chicken B-lymphocyte DT40 cells, SLDR depends on homologous recombination repair where RAD54 especially plays a more important role than RAD52, XRCC2,XRCC3, RAD51C and RAD51D.
https://www.ncbi.nlm.nih.gov/pubmed/11302764
https://www.ncbi.nlm.nih.gov/pubmed/17229998
In mammalian cells, SLDR depends on Ku-dependent (classical) non-homologous end-joining (NHEJ) repair. SLDR occurs after exposure to low-LET radiation, but not that to high-LET radiation.
https://www.ncbi.nlm.nih.gov/pubmed/26189733
https://www.ncbi.nlm.nih.gov/pubmed/23746696
In mammalian cells, SLDR occurs after exposure to low-LET radiation, but not that to high-LET radiation. One explanation is that high-LET radiation inhibits Ku-dependent NHEJ.
https://www.ncbi.nlm.nih.gov/pubmed/808829
https://www.ncbi.nlm.nih.gov/pubmed/16392963
https://www.ncbi.nlm.nih.gov/pubmed/18325854
In addition to tumors refractory to conventional photons, carbon ion radiotherapy utilizes hypofractionation regimens for radioresponsive tumors, e.g., delivery of 40 or 50 Gy in 2 to 16 fractions for lung cancer, prostate cancer, and hepatocellular carcinoma.
https://www.ncbi.nlm.nih.gov/pubmed/25638685
https://www.ncbi.nlm.nih.gov/pubmed/27376030
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