RAMPART - RAdiomics and Modeling for ProstAte RadioTherapy


The general objective of the project is to generate new methods and tools allowing the exploitation of the very large amount of available heterogeneous data (mostly imaging, and also contextual and biological data) for toxicity and tumor recurrence prediction within the context of prostate cancer radiotherapy. “Radiomics” is a concept in which high-throughput extraction of quantitative imaging features is used aimed at creating mineable databases from radiological images, which might reveal quantitative predictive or prognostic associations between images and medical outcomes. Such an approach could also allow improving the predictive models of both tumor response and organs-at-risk (OAR) toxicity. The final objective is to better adapt radiotherapy for individuals suffering from prostate cancer, by fully taking advantage of the most recent irradiation techniques, such as intensity modulated and guided adaptive radiotherapy (IMRT, ART, IGRT).

A large amount of heterogeneous data from 2500 prospective patients coming from different observation modalities will be integrated: i) Image data such as computed tomography (CT), cone beam CT (CBCT), MRI and PET; ii) patient clinical history, presented toxicity and recurrence events; iii) Therapy records, such as dosimetric data (dose volume histogram and 3D dose distribution) and iv) biological markers of radio-induced lethality (apoptosis, genetic polymorphism) and inflammation. Hence, by integrating all the available data, the aim of the project is the establishment of new statistical predictive models of digestive and urinary toxicities and recurrence following prostate cancer radiotherapy.

The major breakthrough of the present project is the original integration of dosimetric/imaging and biological data within the models, which is currently rare in the literature, especially for large cohorts. The complex urinary toxicity will be particularly explored. The design of these models will also allow identifying highly sensitive sub-volumes within the whole urinary and digestive structures, as well as dominant intraprostatic tumor, and could be used for tailoring of personalized adaptive radiotherapy treatments . Personalized treatments are expected to have a strong impact on patients outcome by significantly decreasing side effects and simultaneously increasing curability following prostate cancer radiotherapy.



Geniturinary Toxicity after Prostate Radiotherapy

Urinary toxicity in prostate cancer patients after high dose  radiation therapy (RT) is recognized as the the most important long term problem. With dose escalation aiming at  higher locoregional control, at least half of all patients require symptomatic management of acute toxicities. However, urinary symptoms are usually versatile, and their correlation with underline dose-volume characteristics is not yet fully understood.  In fact, genitourinary symptoms can originate in any part along the genitourinary tract, including the prostate, bladder, and the prostatic urethra, and thus it is difficult to identify which regions are related to a given toxicity. Especially prostatic urethra and the bladder neck, which are unavoidably included in the target volume, are possibly responsible for a number of urinary symptoms. Given the difficulty to separate the bladder and urethra - related toxicities, the contribution of prostatic urethral inflammation to the development of symptomatic acute and late urinary toxicity has not been sufficiently quantified.

It is our belief that a modeling approach addressing all relevant urinary structures (e.g. bladder trigone and prostatic urethra) would better elucidate the dose-volume relationship regarding urinary toxicity. There are isolated reports emphasizing the value of delineating the  urethra as a volume at risk with the possibility of improving genitourinary  toxicity. However, the computation of urethral doses is not simple; as the organ lies within the prostate, it is not visible on planning CT images and consequently, its identification for dose assessment has been a challenging task.

In order to address this issue, our study aims to i) segment the urethra from planning CT scans based on an in-house developed atlas based method (as depicted in figure 1) ii) to quantify the dose received by the urethra (figure 2) and iii) determine clinical and dosimetric predictors for urethral-related symptoms after prostate radiotherapy.




Figure 1 : Prostatic urethra segmentation




Figure 2 : DVH



A possible relationship between urinary toxicities and dose to prostatic urethra is expected to lead to recommendations for precise assessment of these doses, in order to better predict radiation-induced toxicities and to allow for development of techniques that minimize genitourinary symptoms.