Investigating the relative biological effectiveness of clinically relevant photon energies and the intrinsic radiosensitivity of human cancer cell lines towards biologically informed radiotherapy treatments
Notice bibliographique
Résumé
With more than half of cancer patients undergoing ionizing radiation at some point in their treatment, radiotherapy stands as a crucial and fundamental modality in cancer management. Despite technological advancements, the difference in effectiveness between photon sources with variable energies remains inadequately characterized. Current standards, such as those recommended by the International Commission on Radiological Protection (ICRP), assign relative biological effectiveness (RBE) of unity to all photon sources, a simplification that overlooks significant biological variability. The biological response to radiation quality is also influenced by a cancer’s inherent sensitivity to radiation, influenced by its proficiency in recovering from the damage incurred by the ionizing radiation. Therefore, this thesis aims to characterize the variable RBE for clinically relevant photon sources and explores DNA repair capacity as a biomarker for intrinsic radiosensitivity in cancer cells.In the first part of this thesis, the RBE of clinically relevant high and low photon energies was characterized in vitro for three human cancer cell lines: HCT116 (colorectal), HeLa (cervical), and PC3 (prostate). Cells were irradiated using 6 MV x-rays from a linear accelerator, an 192Ir brachytherapy source, and 225 kVp and 50 kVp orthovoltage x-rays. Cell survival post-irradiation was assessed using clonogenic assays, and survival fractions were fitted using the linear quadratic model. Our findings revealed that cell-killing efficiency increased with decreasing photon energy. Using 225 kVp x-rays as the reference, the RBEs for HCT116 with 6 MV x-rays, 192Ir, and 50 kVp x-rays were 0.89 ± 0.03, 0.95 ± 0.03, and 1.24 ± 0.04, respectively. For HeLa, the RBEs were 0.95 ± 0.04, 0.97 ± 0.05, and 1.09 ± 0.03, and for PC3, the RBEs were 0.84 ± 0.01, 0.84 ± 0.01, and 1.13 ± 0.02, respectively. In the second part of the thesis, we measured the DNA repair kinetics following sublethal damage in four human cancer cell lines (HCT116, HT29, HeLa, and PC3) to investigate molecular mechanisms for variable cell survival further. Cells were subjected to split-dose irradiations of 4 Gy of 225 kVp x-rays delivered in 2 × 2 Gy fractions at varying time increments (0 - 10 hours) between fractions. Resultant survival fractions assessed with clonogenic assays were plotted as a function of inter-fraction time and fitted with the Lea-Catcheside modified linear-quadratic model. The estimated repair half-lives for the four cancer lines corroborate the surviving fraction at 2 Gy (SF2Gy) measured in our RBE studies, with HT29 being most radioresistant (Trepair = 64 ± 21 min), followed by HeLa (Trepair = 118 ± 61 min), PC3 (Trepair = 120 ± 18 min), and HCT116 (Trepair = 215 ± 87 min) being the most radiosensitive. An observed correlation between repair half-lives and SF2Gy lends a viable possibility for using DNA repair kinetics as a new biomarker for intrinsic radiosensitivity.This research highlights the need to consider photon energy-specific RBEs and DNA repair capacities in radiotherapy planning. By refining our understanding of these factors, we can enhance the precision of cancer treatments, improve therapeutic ratios, and ultimately achieve better patient outcomes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».