Thesis

3D nanodosimetry for proton therapy treatment planning

• Call:

  ProtoTera Call 2020

• Academic Year:

  2020/2021

• Supervisor:

  Ana Belchior

• Co-Supervisor:

  Reinhard Schulte

• Host Institution:

  C2TN - Centro de Ciências e Tecnologias Nucleares

• Granting Degree Institution:

  Instituto Superior Técnico (Universidade de Lisboa)

• Typology:

  Mixed

• Abroad Institution:

  Instituto Superior Técnico (Universidade de Lisboa)

• Abroad Supervisor:

• Abstract:

  Radiation therapy requires absorbed dose verification to guarantee accurate delivery of a carefully planned and optimized treatment scheme. In modern radiation therapy, the solution of an "optimal" plan is usually found by mathematically solving an inverse problem, where the physician prescribes the minimum required dose to the tumour and maximum allowed doses to healthy tissues (organs at risk) and a mathematical algorithm finds a solution in the fluence vector space. Each individual of many pencil beams is delivered with the required fluence such that the desired prescribed dose distribution is obtained. This method works not only well for intensity-modulated photon radiotherapy (IMRT) but also for intensity-modulated proton therapy (IMPT). The precalculated dose distribution still needs to be validated before treatment with a patient-specific QA procedure, which requires a 3D ionization chamber matrix. For charged particle therapy using protons or ions, verification of the absorbed dose is not sufficient. We need to plan and verify the microscopic, or better, the nanoscopic dose distribution. On very small (nanometer) spatial scales, the energy imparted to a given microscopic volume, e.g., a DNA segment of 1-2 helical turns, is a stochastic quantity. Since ionization is considered the most consequential form of energy deposition in radiobiology, ionization cluster size distributions are fundamental for nanodosimetry. Certain quantities, such as the cumulative frequency of more than j ionizations (Fj), where j could be 2, 3, 4, etc., can characterize the biological effect and serve as upper and lower bounds in a constrained dose optimization problem. We are proposing to replace the problem-loaded concept of relative biological effectiveness (RBE) with a nanodosimetric concept of ionization detail (ID), a physical quantity that can be calculated, optimized, and measured using a compact gas-based nanodosimeter, just like macroscopic dose during treatment planning is calculated and then verified. Nanodosimetry started many years ago, initially with large, mostly stationary nanodosimeters built in several laboratories in Europe and at Loma Linda University (LLU) in the U.S. In recent years, investigators at LLU have built prototypes of a more compact nanodosimeter that needs to be further developed and optimized but could eventually be used to do point measurements of nanodosimetric distributions in a matrix-like 3D nanodosimeter. The PhD activities will be developed at C2TN and at LLU in the U.S. to test the next-generation prototype of a compact nanodosimeter. For the planned experiments, we will utilize a modern proton therapy centre (Northwestern Medicine Proton Therapy Center in Warrenville, Illinois). The project investigators will jointly direct the research at C2TN and LLU. They will meet weekly on Zoom. The LLU supervisor (Professor Reinhard Schulte) is a leading expert in nanodosimetry. The supervisors at C2TN (Ana Belchior) features robust and mature understanding of nanodosimetry and its relation to radiobiology, biological dosimetry, and cytogenetics, as well as a sustained level of international collaborations. Over the years, they have participated in projects and networks of excellence and have published in the scientific domains of relevance. The balance and synergies between the supervisors' expertise will be an added value to attain the proposal's objectives. Access to state-of-the-art irradiation facilities, laboratories, and equipment will be available at the institutions mentioned above.