Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Kouris Panagiotis
Dissertation committee:
Ευάγγελος Παντελής, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βασίλειος Κουλουλίας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παντελής Καραΐσκος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σεϊμένης Ιωάννης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παναγιώτης Παπαγιάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Λουκάς, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργία Λυμπεροπούλου, Λέκτορας, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μελέτη της επίδρασης του ρυθμού χορήγησης της θεραπευτικής δόσης στον θεραπευτικό λόγο σύγχρονων κλινικών εφαρμογών ακτινοθεραπείας
Translated title:
Study of the dose rate effect on the therapeutic scheme of modern radiotherapy clinical applications
Summary:
In the first part of the doctoral dissertation the dose rate distributions delivered to 55 prostate and head & neck (H&N) cancer patients treated with a helical TomoTherapy (HT) system were resolved and assessed with regard to pitch and field width defined during treatment planning. Potential loss in the bio-effectiveness of HT treatments due to sublethal repair mechanisms triggered during dose delivery was estimated using the concept of biologically effective dose (BED) and acknowledging two independent, equally contributing repairing mechanisms with repair halftime of 0.19 h and 2.16 h. Statistical analysis of the studied cases showed that the median treatment delivery time was 4.4 min and 6.3 min for the prostate and H&N cases, respectively. Dose rate volume histogram data for the studied cases showed that the 25% and 12% of the volume of the planning target volumes of the prostate and H&N cases are irradiated with a dose rate of greater or equal to 1 Gy/min. Quartile dose rate (QDR) data confirmed that in HT, where the target is irradiated in slices, most of the dose is delivered to each voxel of the target when it travels within the beam. Analysis of the planning data from all cases showed that this lasts for 68 s (median value). QDRs showed that using the 2.5 cm field width, 75% of the prescribed dose is delivered to target voxels with a mean dose rate of at least 3.2 Gy/min and 4.5 Gy/min, for the prostate and H&N cases, respectively. Systematically higher dose rates were observed for the H&N cases due to the shallower depths of the lesions in this anatomical site. Delivered dose rates were also found to increase with field width and pitch setting, due to the higher output of the system which, in general, results in accordingly decreased total treatment time. BED results for finite (clinical) dose rate delivery accounting for sublethal repair were found in agreement with corresponding calculations for instantaneous treatment delivery, suggesting negligible loss in treatment bio-effectiveness both for the prostate and H&N cases. Ιn IMRT appears to be no effect of treatment time and consequently dose rate on bio-effectiveness when the treatment time is of the same order of magnitude or less than the repair half-time. However, an effect is expected on radiotherapy techniques with fairly longer treatment time such as stereotactic radiosurgery.
The diversity in technical configuration among the clinically available radiosurgery systems, results in accordingly diverse treatment times for the same physical dose prescription, spanning from several min to more than 1h. This, combined with evidence supporting the impact of dose delivery temporal pattern on the bio-effectiveness of low LET radiation treatments, challenges the assumption of acute dose delivery commonly employed to estimate the clinical outcome using the concept of Biologically Effective Dose (BED). In the second part of the doctoral dissertation, the treatment plans of 30 patients underwent CyberKnife radiosurgery for Vestibular Schwannomas (VS), prescribing a marginal dose of 13 Gy to the tumor in a single fraction, were retrospectively reviewed and the derived dose distributions were resolved in the temporal domain. It was demonstrated that CyberKnife radiosurgery greatly departs from the assumption of acute exposure, delivering highly inhomogeneous dose rate distributions in the temporo-spatial domain, even for single fraction treatments. This influences the delivered BED due to alterations in the sublethal damage repair (SLR) occurring within the treatment session. The net effect on BED of SLR alterations becomes considerable for treatments lasting longer than the faster repair component half time. Using a BED model involving SLR effects, it was shown that each physical dose iso-surface is associated with a BEDslr range which can be represented by the corresponding mean value and standard deviation (1σ). The range of BEDslr values per isosurface depends on the plan optimization steps. For the studied VS cases cohort, a typical range of 2%, with respect to the mean BEDslr value was found at 1σ. The marginal BEDslr delivered to the VS tumors through the prescription dose iso-surface was found to deteriorate with treatment time, involving both beam-on time and beam-off gaps. Using linear regression fitting models, the marginal BEDslr for 13 Gy prescription can be estimated with reasonable uncertainty. Compared to the acute exposure approach, a BED “loss” of 21% is associated with the delivery of 13 Gy to the VS tumor in 35 min.
Main subject category:
Health Sciences
Keywords:
Medical physics, Radiotherapy, Radiobiology, Intensity Modulated Radiation Therapy, Stereotactic Radiosurgery
Number of references:
216
