Browsing by Author "Quon, Harvey"

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    Application of Machine Learning in Prostate Cancer External Beam Radiation Therapy to Improve Biochemical Failure-Free Survival Prediction
    (2022-08-24) Sun, Lingyue; Smith, Wendy; Kirkby, Charles; Brown, Jo-Anne;; Quon, Harvey; McGeachy, Philip
    Curative external beam radiation therapy (EBRT) is a common treatment option for localized prostate cancer. The reported biochemical failure-free survival (BFFS) for prostate cancer patients post-EBRT varies significantly. The current, widely implemented clinical models that are used to predict treatment outcome for these patients have limited reliability. This thesis aims to examine the possible sources of influence on BFFS and improve EBRT treatment outcome prediction in terms of BFFS in particular using machine learning (ML) algorithms.Radiotherapy clinical trial protocols are adopted by different institutions due to their promising outcome(s) and/or superior efficiency. In this thesis, we first quantified the plan quality differences across four institutions in Alberta for PROstate Fractionated Irradiation Trial (PROFIT) plans. Despite the common guiding protocol, we observed statistically significant differences in dosimetric parameters between institutions; however, outcome modeling suggested such differences were of minimal clinical consequence.There is a need for more detailed understanding of the relationships between EBRT treatment planning and treatment delivery-related features and tumor control outcomes. We investigated the EBRT-related features that may be prognostic of BFFS using a random survival forest model. We found that the clinical target volume D99, pelvic irradiation, IGRT frequency, and planning target volume V98 were prognostic in addition to a set of tumor features.We then investigated whether ML-based models that incorporated additional EBRT treatment planning and delivery related features could perform better than the clinical models that were exclusively based on patient demographic and tumor features. We found that the two ML-based models outperformed the two clinical models on both the training and validation datasets, although all models’ performances deteriorated against the validation dataset.To further improve BFFS prediction, we investigated whether adding dosiomic features, which contains spatial information about the planned 3D dose distribution, could enhance the model performance. We did find improvement, and such improvement although relatively small was maintained when the model was validated with patients from other institutions. Additionally, we evaluated the impact of dose calculation variations on dosiomic features and found that most dosiomic features were stable against variations in dose calculation algorithms, versions, and dose grid.
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    Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial
    (2021-11-04) Kim, Julian O.; McDonald, Megan O.; Ong, Aldrich; Koul, Rashmi; Dubey, Arbind; Hunter, William; Ahmed, Shahida; Quon, Harvey; Yee, Don; Parliament, Matthew; Sivananthan, Gokulan; Danielson, Brita; Rowe, Lindsay; Ghosh, Sunita; Usmani, Nawaid
    Abstract Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.