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Improving physical dosimetry and developing biologically-relevant metrology for spot-scanned proton therapy beams

Final Report Summary - PROTONSPOTSCANMET (Improving physical dosimetry and developing biologically-relevant metrology for spot-scanned proton therapy beams)

Proton therapy is an advanced form of radiotherapy which has the potential to deliver a dose map that closely matches the tumour volume. This project sought to resolve some of the unanswered questions surrounding quality assurance in spot-scanned proton therapy. The research performed can be divided into two main categories: physical and biological dosimetry.

PHYSICAL DOSIMETRY: This part of the project focused on the metrology of individual proton tracks. We irradiated a series of Fluorescent Nuclear Track Detectors (FNTDs) at Massachusetts General Hospital, using a mono-energetic proton beam. In parallel, we simulated the proton energy depositions down to the nanometre scale, using the TOPAS-nBio Monte Carlo platform. Together with collaborators from MD Anderson we set up a protocol to image the FNTDs using a confocal laser scanning microscope. We developed an analysis pipeline to extract imaged parameters for proton tracks at different positions along the proton beam’s path.

Outcomes: using FNTDs we were able to experimentally replicate the trends that we observed in our TOPAS-nBio simulations. Our results represent an important first step towards the experimental validation of Monte Carlo simulations on the sub-cellular scale and demonstrate that FNTDs enable experimental study of the microdosimetric properties of individual protons.

Dissemination reference: Underwood TSA et al, doi: 10.1088/1361-6560/aa6429

BIOLOGICAL DOSIMETRY: Here our focus was to better understand the uncertainties associated with the biological effectiveness of proton beams. Initially, we performed radiobiological modeling for patients with prostate cancer. We then sought to perform a clinical investigation of proton radiobiology via quantitative analysis of breast cancer patient images taken after treatment.

Radiobiological modelling: There exists strong clinical motivation to treat patients with a small number of proton beams. However, published models predict that proton beams have an elevated relative biological effectiveness (RBE) at their distal edge, so that proton beam angles must be selected carefully. In this work we combined TOPAS Monte Carlo simulations with radiobiological modelling for prostate patients. We considered patient cohorts treated with and without rectum spacer gel insertion (a novel protocol designed to better spare the rectum during radiotherapy).
Outcomes: for the cohort without rectum spacer gels, our research indicated that use of anterior proton beams was not appropriate. However, for the second cohort, we found that the rectum spacer gels suitably mitigated the biological uncertainties associated with such beams.

Dissemination references: Underwood TSA et al doi: 10.1080/0284186X.2016.1275781 Underwood TSA et al doi: 10.1016/j.ijrobp.2016.01.018 Underwood TSA et al doi: 10.1016/j.ijrobp.2015.10.006 Underwood TSA et al doi: 10.1259/bjr.20180004

Clinical investigation of proton radiobiology: Clinically, proton therapy centres assume a fixed RBE of 1.1. Many radiobiological models have been develop to elucidate distal edge RBE variation, but these are typically based on data from cell experiments. In-vivo validation of such modelling has so far proved challenging. In this work we performed an analysis of CT scans taken after proton therapy, to consider the biological effects of protons upon healthy lung tissue.

Outcomes: Our results indicated that clinically relevant proton relative biological effectiveness exceeds 1.1 under certain circumstances. Our published study (referenced below) is one of only two which have studied proton RBE within patients.

Dissemination reference: Underwood TSA et al doi: 10.1016/j.ijrobp.2018.03.037

Overall impacts of the project
Our work has:
• contributed to the validation of computer simulations which have the potential to underpin new developments in proton therapy
• guided treatment planning protocols for prostate patients treated using proton therapy
• provided important clinical evidence that distal edge RBE effects are important within patients as well as in cellular experiments

In addition, the project has enabled the research fellow to develop her own career by:
• gaining clinical experience of proton therapy within a leading U.S. department
• advancing her scientific skills by working with world-leaders in her field

Students and members of the public have also benefitted from outreach schemes which the fellow was involved in, including:
• “The Art of Talking Science”, a presentation event organised as part of HUBweek, a Boston-wide initiative designed to engage the public in science, technology and art
• The Dana-Farber / Harvard Cancer Center CURE program. A mentorship scheme which introduced cancer research to high school and college students from under-represented populations