Today we are going to introduce one of our wonderful PhD graduates: Dr. Marco Marcello.
Marco started his Bachelor of Science (Physics) in 2010 and completed a Master of Medical Physics in three semesters, followed by a PhD at UWA.
Marco was awarded a PhD in May 2020 and soon after, he was accepted as a Radiation Oncology Medical Physics Registrar (TEAP Training Position) at Sir Charles Gairdner Hospital (SCGH).
His research project was on “Voxel-wise association of planned dose with measures of treatment failure and toxicity in prostate external beam radiotherapy” supervised by Adj/Prof. Martin Ebert and Dr. Pejman Rowshanfarzad.

Dr. Marco Marcello, UWA Medical Physics Graduate

Here is what Marco’s principal supervisor, Adj/Prof. Martin Ebert, had to say about his performance:

“I first supervised Marco’s research during his Masters program where he boldly ventured into the world of biostatistics, using the associated skills to discover what factors can influence the outcomes of prostate radiotherapy treatment. Marco was so adept that I was very pleased when he decided to pursue a PhD in the same area.
During his PhD, Marco invented a completely novel way of working out how radiotherapy treatments can lead to side-effects in patients. He collaborated with clinicians and researchers from around Australia and the United Kingdom to publish his results in major international journals. His work will now influence others and we are hopeful this will lead to new ways of planning patient treatments that minimise side-effects.
Marco’s mature approach to his research and excellent communication skills were essential ingredients for his success. I am very pleased that Marco is now able to undertake TEAP training towards clinical registration. With the knowledge he developed through his PhD and skills he will acquire in TEAP, I am confident Marco will go on to help many patients and continue to contribute to the practice of medical physics.”

And here are comments from Marco’s coordinating supervisor, Dr. Pejman Rowshanfarzad:

“It was a great pleasure to work with Marco as his coordinator supervisor and a friend. Marco was one of the few MSc graduates who managed to publish their Masters project results. As a student, Marco was very responsible and regularly presented his work progress to supervisors. He was an excellent communicator and very enthusiastic about his project. Towards the end of his PhD, he spent extra hours every day and over the weekends to provide high quality work while meeting deadlines. Marco was a high achiever and published the outcome of his PhD work in multiple peer reviewed journals and conferences.
He was also a student representative and helped with lots of arrangements for student activities. Marco was always kind and considerate, treated everyone with respect, took part in both social and scientific gatherings, and showed a great sense of mateship. He helped other students with their projects in areas where they were lacking skills, such as programming.
Marco worked in short term jobs for Genesis CancerCare WA and 5D Clinics, and voluntarily attended Physics QA sessions at SCGH. These gave him an idea of what to expect in a clinical work environment and prepared him for his current clinical training position.”

Marco kindly accepted to answer a few questions about his experience in our Medical Physics research Group.

  • Introduction and your current position and role: Hi there, my name is Marco and I’m currently a Radiation Oncology Medical Physics Registrar undertaking the TEAP program in the Medical Physics team at Sir Charles Gairdner Hospital.
  • What did you enjoy most about UWA, and Medical Physics research group?
    Although many aspects of research I found challenging, I enjoyed using MATLAB to perform the 3D statistical analysis required for my project and see some intriguing results emerge from it, and getting to know the other students and their projects and watching them make progress.
  • Can you give us your top three reasons to study Medical Physics?
  1. It connects physics to an important application in the real world. For example, you can use your physics skills to help provide safe and effective radiotherapy – a crucial service for the benefit of the community.
  2. You are able to work with some of the most sophisticated technology in medicine, such as linear accelerators, CTs and MRIs, and their associated software packages.
  3. It can lead to a secure and rewarding career.
  • How do you feel you have made a difference in your field of research?
    My research was exploratory and preliminary work, and so I feel I have laid a foundation for others to build upon in the future. Hopefully their work will be to translate my results to the clinic to help maximise tumour control and minimise complications from using statistically based models.
  • What is your best advice to current students and Medical Physics applicants?
    Get involved and ask lots of questions. I regret not volunteering in more clinical work early on in my studies and I also regret not asking questions and exploring answers where I had ambiguities. Most clinical physicists will be happy to take you along to much of their routine work. There’s no substitute for seeing how medical physics work is done in the clinic first hand, and it will even benefit your research.

Here is the abstract of Marco’s thesis:
External beam radiotherapy (EBRT) is a prominent treatment option for prostate cancer. The goal of all radiotherapy, including EBRT, is to deliver adequate radiation dose to the prostate tumour while minimising dose to the surrounding healthy organs at risk (OARs). Advancements in EBRT technology have enabled more spatially conformal treatments, reducing dose to OARs.
The reduced margins associated with these treatments risk inadequately treating microscopic cancer in the immediately periphery of the prostate. Understanding the relationship between dose coverage of microscopic disease and resulting treatment failure may help improve tumour control. No study to date has performed a comprehensive voxel-wise analysis relating dose and treatment failure throughout the entire pelvic anatomy, validated across multiple datasets. This formed the first aim of this study.
Although toxicity related symptoms associated with dose to healthy organs have decreased as a result of more conformal treatments, they still impact quality of life of prostate EBRT patients. Understanding the relationship between toxicity symptoms and the spatial distribution of dose at OAR sites and throughout the pelvic anatomy will help determine more optimal dose constraints which may reduce toxicity incidence. Voxel-wise studies have discovered correlation between spatial dose features and both gastrointestinal (GI) and genitourinary (GU) symptoms at surfaces and volumes of OARs, such as the rectum and bladder. These studies have not explored all OARs throughout the pelvic anatomy and have always assumed that dose-toxicity relationships occur at OARs. Therefore, a further aim of this study was to associate dose with GI and GU toxicity symptoms throughout the entire pelvic anatomy without this assumption.
Planned 3D dose distributions for 683 prostate EBRT patients from the RADAR TROG 03.04 trial were used as the primary dataset. 388 and 253 prostate EBRT patients from the RT01 and CHHiP trials respectively were used for validation. All dose distributions were deformably registered onto a single exemplar CT image, acting as a common anatomical template. RADAR dose distributions were registered onto two other CT image templates for registration validation. Three independent voxel-wise tests were performed to associate dose with measures of treatment failure (overall survival, PSA progression and local progression), GI (rectal bleeding and tenesmus) and GU (dysuria, haematuria, incontinence and frequency) toxicity throughout the pelvic anatomy. These were voxel-wise applications of a dose-difference permutation test, univariate Cox regression, and multivariate Cox regression with LASSO voxel selection. These tests were performed on the three trial datasets individually, as well as on a combined dataset comprised of all trial patients.
This was the first voxel-wise study to avoid the assumption that associations necessarily occur within the CTV or at traditional organ sites. It was also the first voxel-wise study to operate throughout the broader pelvic region, allowing dose-outcome relationships to be related to treatment technique as well as unexpected local anatomy.

Treatment failure
The voxel-wise tests revealed regions where reduced dose was correlated with measures treatment failure. The dominant pattern was an association between reduced dose at the prostate posterior and increased failure, across all three measures. Reduced dose to the seminal vesicle region was also associated with increased failure for the RADAR dataset. Adequately treating the posterior prostate and immediately surrounding posterior region may improve tumour control, acknowledging the increased risk of rectal toxicity with extended posterior margins.

Gastrointestinal toxicity
The voxel-wise tests determined anatomically localised dose-toxicity relationships. High doses (>55 Gy) in a small volume of the central rectum adjacent to the CTV were associated with rectal bleeding, while low-intermediate doses (~25 Gy) throughout the peri-rectal fat space (PRFS) at the posterior of the rectum were associated with tenesmus. The serial response of the rectum with respect to rectal bleeding and the parallel response of the PRFS with respect to tenesmus were demonstrated.

Marco’s publications are listed here:

  • Similarity clustering-based atlas selection for pelvic CT image segmentation
    Kennedy, A., Dowling, J., Greer, P. B., Holloway, L., Jameson, M. G., Roach, D., Ghose, S., Rivest-Henault, D., Marcello, M. & Ebert, M. A., May 2019, In : Medical Physics. 46, 5, p. 2243-2250 8 p.
  • Association between measures of treatment quality and disease progression in prostate cancer radiotherapy: An exploratory analysis from the TROG 03.04 RADAR trial
    Marcello, M., Ebert, M. A., Haworth, A., Steigler, A., Kennedy, A., Bulsara, M., Kearvell, R., Joseph, D. J. & Denham, J. W., 1 Apr 2018, In : Journal of Medical Imaging and Radiation Oncology. 62, 2, p. 248-255 8 p.
  • Association between treatment planning and delivery factors and disease progression in prostate cancer radiotherapy: Results from the TROG 03.04 RADAR trial
    Marcello, M., Ebert, M., Haworth, A., Steigler, A., Kennedy, A., Joseph, D. & Denham, J., 1 Feb 2018, In : Radiotherapy and Oncology. 126, 2, p. 249-256 8 p.
  • Spatial, Anatomically-Localized Mapping of Dose-Toxicity Associations Following Prostate Radiotherapy
    Marcello, M., Kennedy, A., Dowling, J., Haworth, A., Holloway, L., Gulliford, S., Dearnaley, D., Denham, J. & Ebert, M., Jun 2018, In : Medical Physics. 45, 6, p. E446-E446 1 p.

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