Stereotactic MR-guided Adaptive Radiation Therapy (SMART) for localized prostate cancer; a phase II study

External beam radiotherapy (EBRT) is the treatment of choice in a substantial
proportion of patients with localized prostate cancer (cT1c-T3N0M0).
Total doses and dosage per fraction plays an important role in the treatment of
prostate cancer and the side effects of treatment. Several studies have proven
these hypofractionated schemes to be equally efficient and tolerated as well as
conventionally fractionated treatments, with the advantage that treatment can
be delivered within two weeks [King et al, Radiother Oncol, 2013, Katz et al,
Front Oncol, 2014, Henderson et al, Clin Oncol, 2015].

The clinical introduction of stereotactic MRI-guided adaptive radiation therapy
(SMART) using the MRIdian treatment machine will enable visualisation of target
volume and adjacent normal organs such as the rectum and bladder prior to- and
during treatment delivery. Online imaging allows to deliver *gated* treatment,
enabling the use of small uncertainty margins, which can potentially limit
clinical toxicity. One further advantage of the SMART approach for prostate
cancer is the ability to perform adaptive treatment planning for each delivered
fraction. This means that the original treatment plan can be optimized
immediately prior to treatment delivery, especially optimized with respect to
the position and size of the adjacent normal organs such as the rectum and
bladder.

The main objective of this phase II observational study is to investigate the
early and early-delayed toxicity in 100 patients with localized prostate cancer
(cT1c-T3bN0M0) that is observed in the first year following after stereotactic
MRI-guided adaptive radiation therapy (SMART) using the MRIdian treatment
machine of the adjacent normal organs, after daily adapting the treatment plan
before every fraction on the anatomy of that day.




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The study is a prospective phase II observational trial

This novel SMART approach could set a new standard of care for patients with
localized prostate cancer by limiting radiation doses to surrounding normal
organs and thereby potentially radiation-induced toxicity. Also, implantation
of gold markers would become unnecessary using MR-guided *gated* radiotherapy.
Disadvantages for patients include the need to be positioned within the MRI
bore during radiation delivery, and a prolonged time per treatment fraction
(estimated at 30 minutes per fraction), which has to be weighed against the use
of a total of only five fractions. As the radiation fractionation scheme that
is used in this study has been evaluated in prior trials, no further
patient-related risks are anticipated.


Patients will be followed-up with the frequency according to Dutch guidelines
for localized prostate cancer.The extra time for filling in the questionnaires
will be around 5-10 minutes.