HYPo-fractionated Radiotherapy of Lymph Node Metastases guided by NanO-MRI in Prostate Cancer Patients: A Pilot Study (HYPNO-study)

In patients with biochemical recurrent prostate cancer after radical
prostatectomy early local salvage radiotherapy to the prostatic fossa offers a
second option for treatment with curative intent. However, in a substantial
number of patients a secondary biochemical recurrence occurs due to metastatic
disease, e.g. in regional lymph nodes or as distant metastases.
Recent developments in imaging of recurrent prostate cancer patients, such as
PSMA-PET/CT, enable earlier detection of a local and regional/distant
recurrence, thereby identifying patients who may benefit of local treatment and
those in which unnecessary local radiotherapy can be omitted. Although patients
with regional metastases have historically been regarded as incurable,
high-precision, high-dose-per-fraction radiotherapy techniques have shown to be
able to eradicate oligo-metastatic disease, thereby leading to a prolonged
progression-free survival and delay of systemic therapy or, in a subgroup of
patients, potentially cure. Several reports have mentioned the safety and
tolerability of this so-called stereotactic body radiotherapy (SBRT) to pelvic
lymph nodes. The introduction of dedicated treatment machines integrating
MR-imaging with linear accelerators (MR-linac) are expected to improve SBRT
accuracy even more by daily adaptive treatment planning based on online imaging
with high soft tissue contrast.
Nano-MRI has shown to be able to detect lymph node metastases down to a size of
2 mm, which may be well below the resolution of PSMA-PET/CT. Using the ability
of nano-MRI to detect such small lymph node metastases, lymphatic prostate
cancer recurrences could be detected at a very early stage making an early
local SBRT of the recurrent lymph nodes possible. The high-spatial resolution
of nano-MRI when used in combination with MR-Linac can enable very precise,
individually tailored SBRT options for oligometastatic lymph node spread in
prostate cancer patients. Also, implementation of nano-MRI may improve the
stratification of patients for local or regional therapy, thereby preventing
overtreatment of the prostatic fossa and undertreatment of small pathologic
lymph nodes.

To evaluate the feasibility and efficacy of MR-guided stereotactic body
radiotherapy (SBRT) to nano-MRI detected regional lymph node metastases in
patients with biochemical recurrent prostate cancer after radical
prostatectomy.

Single-arm, single-center prospective feasibility study, phase IIA according to
the R-IDEAL framework.

Participating patients will undergo nano-MRI imaging, including the infusion of
the ferumoxtran-10 contrast agent.

Patients who are eligible for stereotactic radiotherapy will be treated 5 x on
the MR-linac with an overall treatment time of 2 weeks (approximately 1 hour
per treatment). This replaces the 'standard' radiation treatment of the
prostatic fossa consisting of 26 fractions with an overall treatment time of
6.5 weeks (approximately 10 minutes per treatment).

Investigation and treatment:

Eight hospital visits in 5 weeks (approximately 1 hour per visit).
These visits consist of:

1) MRI of the prostatic fossa, followed by infusion of nano-contrast agent.
2) one day later nano-MRI for lymph node imaging.
3) one week later planning CT for preparation of the radiation treatment
(standard of care).
4) two weeks later start of radiation treatment: a total of 5 treatments (one
hour each). This replaces the standard radation treatment of the prostatic
fossa, consisting of 26 fractions (10 minutes each) with an overall treatment
time of 6.5 weeks.

Follow-up

Follow-up is mostly comparable to regular follow-up.
Following treatment the first follow-up visit will take place 6 weeks after
treatment and every 3 months until 1 year after treatment. Thereafter,
follow-up will be once every 6 months until 5 years after treatment. At every
follow-up PSA will be measured.
At 3, 12 and 24 months after treatment an extra nano-MRI will be performed
preceded by infusion of the contrast agent one day earlier. This will take 6
extra visits of approximately one hour each.