A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.
Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space f...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4252029?pdf=render |
| _version_ | 1819047013825642496 |
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| author | Simon D Angus Monika Joanna Piotrowska |
| author_facet | Simon D Angus Monika Joanna Piotrowska |
| author_sort | Simon D Angus |
| collection | DOAJ |
| description | Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy. |
| first_indexed | 2024-12-21T10:53:37Z |
| format | Article |
| id | doaj.art-745c36ac2daa4186836065f6832dc120 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T10:53:37Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-745c36ac2daa4186836065f6832dc1202022-12-21T19:06:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11409810.1371/journal.pone.0114098A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.Simon D AngusMonika Joanna PiotrowskaMulti-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy.http://europepmc.org/articles/PMC4252029?pdf=render |
| spellingShingle | Simon D Angus Monika Joanna Piotrowska A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. PLoS ONE |
| title | A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. |
| title_full | A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. |
| title_fullStr | A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. |
| title_full_unstemmed | A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. |
| title_short | A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search. |
| title_sort | matter of timing identifying significant multi dose radiotherapy improvements by numerical simulation and genetic algorithm search |
| url | http://europepmc.org/articles/PMC4252029?pdf=render |
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