This thesis investigates the cytotoxic hierarchy of three radiotherapy modalities carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon radiation therapy (XRT) in head and neck cancer (HNC) cell models, with a focus on the role of linear energy transfer (LET). Clonogenic survival assays revealed that CIRT achieved the strongest tumor cell suppression, characterized by steep linear survival curves, low LD₅₀ values (<1 Gy), and relative biological effectiveness (RBE) values approaching or exceeding 2.0. Proton therapy provided moderate radiosensitization, reducing LD₅₀ values while permitting partial DNA damage repair, whereas photon therapy was the least effective, producing survival curves shaped by repairable damage. Cell-line-specific differences were observed: SCCNC1 cells exhibited inherent sensitivity to high-LET radiation, reflected by strictly linear survival curves and limited repair capacity; SCCNC4, initially resistant to photons, displayed the most pronounced gain in sensitivity under carbon ion exposure; and ITAC-3 showed intermediate but consistent benefit from both proton and carbon ion treatments. Overall, these findings highlight the superiority of CIRT in overcoming intrinsic or acquired radioresistance, particularly in aggressive HNC subtypes. The results provide preclinical evidence for LET-guided personalized radiotherapy strategies, supporting the integration of carbon ion therapy into treatment protocols for tumors refractory to conventional photon-based approaches.
This thesis investigates the cytotoxic hierarchy of three radiotherapy modalities carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon radiation therapy (XRT) in head and neck cancer (HNC) cell models, with a focus on the role of linear energy transfer (LET). Clonogenic survival assays revealed that CIRT achieved the strongest tumor cell suppression, characterized by steep linear survival curves, low LD₅₀ values (<1 Gy), and relative biological effectiveness (RBE) values approaching or exceeding 2.0. Proton therapy provided moderate radiosensitization, reducing LD₅₀ values while permitting partial DNA damage repair, whereas photon therapy was the least effective, producing survival curves shaped by repairable damage. Cell-line-specific differences were observed: SCCNC1 cells exhibited inherent sensitivity to high-LET radiation, reflected by strictly linear survival curves and limited repair capacity; SCCNC4, initially resistant to photons, displayed the most pronounced gain in sensitivity under carbon ion exposure; and ITAC-3 showed intermediate but consistent benefit from both proton and carbon ion treatments. Overall, these findings highlight the superiority of CIRT in overcoming intrinsic or acquired radioresistance, particularly in aggressive HNC subtypes. The results provide preclinical evidence for LET-guided personalized radiotherapy strategies, supporting the integration of carbon ion therapy into treatment protocols for tumors refractory to conventional photon-based approaches.
In Vitro Survival Analysis of Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines
AGHAJANI, FATEMEH
2024/2025
Abstract
This thesis investigates the cytotoxic hierarchy of three radiotherapy modalities carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon radiation therapy (XRT) in head and neck cancer (HNC) cell models, with a focus on the role of linear energy transfer (LET). Clonogenic survival assays revealed that CIRT achieved the strongest tumor cell suppression, characterized by steep linear survival curves, low LD₅₀ values (<1 Gy), and relative biological effectiveness (RBE) values approaching or exceeding 2.0. Proton therapy provided moderate radiosensitization, reducing LD₅₀ values while permitting partial DNA damage repair, whereas photon therapy was the least effective, producing survival curves shaped by repairable damage. Cell-line-specific differences were observed: SCCNC1 cells exhibited inherent sensitivity to high-LET radiation, reflected by strictly linear survival curves and limited repair capacity; SCCNC4, initially resistant to photons, displayed the most pronounced gain in sensitivity under carbon ion exposure; and ITAC-3 showed intermediate but consistent benefit from both proton and carbon ion treatments. Overall, these findings highlight the superiority of CIRT in overcoming intrinsic or acquired radioresistance, particularly in aggressive HNC subtypes. The results provide preclinical evidence for LET-guided personalized radiotherapy strategies, supporting the integration of carbon ion therapy into treatment protocols for tumors refractory to conventional photon-based approaches.| File | Dimensione | Formato | |
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Thesis Fatemeh Aghajani.docx.pdf
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Descrizione: This experimental thesis investigates the biological effects of three radiotherapy modalities: carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon radiation therapy (XRT) in head and neck cancer (HNC) cell models
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https://hdl.handle.net/20.500.14239/31624