Thesis

Radiobiological effects of photons and protons in glioblastoma multiforme: preclinical studies

• Call:

  ProtoTera Call 2023/1

• Academic Year:

  2023

• Supervisor:

  Antero Abrunhosa

• Co-Supervisor:

  Francisco Alves

• Host Institution:

  ICNAS - Instituto de Ciências Nucleares Aplicadas à Saúde

• Granting Degree Institution:

  Universidade de Coimbra

• Typology:

  Mixed

• Abroad Institution:

  Universidade de Coimbra

• Abroad Supervisor:

• Abstract:

  Glioblastoma multiforme (GBM) is the most common of brain tumors in adults. It is a primary lesion with very aggressive, invasive and undifferentiated characteristics, associated with a poor prognosis. The standard treatment relies on surgical tumor resection followed by combined radiation therapy (RT) and chemotherapy. The average survival is only 15 months and the majority of the patients has a recurrence of disease and eventually dies in a short period of time. The introduction of new approaches for the treatment of GBM is of great importance, and novel therapies are currently under research. The idea of using proton therapy (PT) as a RT alternative in GBM has gain great attention within the scientific community due to the small amount of dose the proton beam delivers when entering the patient’s body and to the dose fall-off after reaching the Bragg peak. The proton beam can be manipulated so that the Bragg peak falls within the tumor site, leading to a higher dose in the lesion while sparing the surrounding healthy tissues. This project aims to evaluate the potential of proton therapy as a therapeutic approach in the treatment of GBM. We will compare the radiobiological effects of X-rays and protons on GBM. For this purpose, a PET-cyclotron-based set-up for proton irradiation will be established at the ICNAS facility. The first stage of radiobiological studies will include the evaluation of viability and survival in human GBM cell lines U87 and U373 when exposed to X-rays. Animal models on GBM will be developed at ICNAS preclinical facility. GBM xenografts will be irradiated with X-rays at CNC and with protons at ICNAS to quantify the effects of radiation in the tumors. In vitro and in vivo studies will be reproduced with a clinical proton beam with energy up to 200 MeV at MD Anderson Cancer Center (MDACC).