Image-guided Focal Brachytherapy Utilizing Combined 18F-DCFPyl PET/CT
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Prostate Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 4/6/2019 |
| Start Date: | April 2019 |
| End Date: | April 2029 |
| Contact: | Daniel Song, MD |
| Email: | dsong2@jhmi.edu |
| Phone: | (410) 502-5875 |
Image-guided Focal Brachytherapy Utilizing Combined 18F-DCFPyl PET/CT and Dynamic Dosimetry With Registered Ultrasound and Fluoroscopy for Localized Prostate Cancer
The Principal Investigator's (PI) working hypothesis is that the PI can utilize the high
predictive value of 18F-DCFPyl PSMA to identify clinically significant tumors in patients who
will undergo brachytherapy, as well as areas which are uninvolved or contain only clinically
insignificant disease.
In the PI's clinical trial, the uninvolved regions (as defined by combined PET-MR-biopsy
data) will not be targeted and receive only fall-off dose, which we have shown to be
associated with reductions in toxicity.
predictive value of 18F-DCFPyl PSMA to identify clinically significant tumors in patients who
will undergo brachytherapy, as well as areas which are uninvolved or contain only clinically
insignificant disease.
In the PI's clinical trial, the uninvolved regions (as defined by combined PET-MR-biopsy
data) will not be targeted and receive only fall-off dose, which we have shown to be
associated with reductions in toxicity.
Current conventional prostate cancer (PCa) imaging modalities (computed tomography, bone
scan, magnetic resonance imaging, ultrasound) have limited accuracy in the initial staging
and for determining prognosis of PCa. Prostate-specific membrane antigen (PSMA) is a cell
surface antigen which is highly expressed in PCa and correlates with prognostic factors such
as Gleason score. High PSMA expression in prostate tumor has been significantly associated
with lethality of disease, allowing specific identification of tumors most in need of
treatment. Combined PET and computed tomography (PET-CT) imaging using small molecules
targeting PSMA-expressing cells have been developed and tested clinically, and have shown
superiority when compared with conventional imaging.
An added advantage of PET compared to MRI is the ability to identify both distant metastatic
disease as well as intraprostatic disease with one imaging modality. PSMA-radiotracers have
continued to evolve since their initial development, with successive improvements in imaging
and diagnostic characteristics. One such second-generation PSMA-binding compound, 18F-DCFPyl,
has been developed and characterized at our institution, and offers superior imaging
qualities compared to prior PSMA-based radiotracers.
In realization of the toxicity of current therapies, there is substantial interest throughout
the urologic oncology community in utilizing focal therapy to mitigate such toxicities. The
rationale for focal therapy is based upon the recognition that whole gland treatment is
associated with unacceptable toxicity rates, while concurrently it is also realized that
patient morbidity and mortality is due to the progression of major foci of high-grade
disease, i.e. the index lesion.
Planning studies have shown that focal brachytherapy is feasible and results in significant
reductions of dose to critical structures. In a historic cohort of patients treated at Johns
Hopkins, the investigators have demonstrated that a modest reduction in dose results in
clinically meaningful reductions in urinary toxicity. Al-Qaiseh et al. found that focal plans
resulted in >50% reductions in dose to urethra and rectum. However, focal plans were highly
sensitive to seed positioning errors, and focal targeting made seed positioning more
critical. This highlights the key utility and importance of the investigators' iRUF system
(integrated Registered Fluoroscopy and Ultrasound) in delivering focal therapy.
The investigators have developed a system of true dynamic intraoperative dosimetry which
utilizes fluoroscopy for seed cloud reconstruction and fusion to transrectal ultrasound
imaging. The investigators previously confirmed this method in a pilot trial of 6 patients
with encouraging results. Further refinement of the system was followed by a Phase II
clinical trial of this integrated platform on a larger group of patients. The investigators
confirmed the primary endpoint to compare intraoperative dosimetric predicted values using
iRUF method vs standard ultrasound-based seed tracking. The iRUF Phase II cohort had
statistically significant improvements in prostate coverage parameters, as well as lower
rates of rectal doses exceeding prescribed tolerance limits when compared to a historical
group of patients. Importantly, there was no trend toward higher prostate V200 doses,
indicating that excellent coverage did not come at the expense of excessive dose within
prostate.
This study will test the combination of PSMA-imaging with iRUF dynamic dosimetry to treat
prostate cancer with a focal approach.
scan, magnetic resonance imaging, ultrasound) have limited accuracy in the initial staging
and for determining prognosis of PCa. Prostate-specific membrane antigen (PSMA) is a cell
surface antigen which is highly expressed in PCa and correlates with prognostic factors such
as Gleason score. High PSMA expression in prostate tumor has been significantly associated
with lethality of disease, allowing specific identification of tumors most in need of
treatment. Combined PET and computed tomography (PET-CT) imaging using small molecules
targeting PSMA-expressing cells have been developed and tested clinically, and have shown
superiority when compared with conventional imaging.
An added advantage of PET compared to MRI is the ability to identify both distant metastatic
disease as well as intraprostatic disease with one imaging modality. PSMA-radiotracers have
continued to evolve since their initial development, with successive improvements in imaging
and diagnostic characteristics. One such second-generation PSMA-binding compound, 18F-DCFPyl,
has been developed and characterized at our institution, and offers superior imaging
qualities compared to prior PSMA-based radiotracers.
In realization of the toxicity of current therapies, there is substantial interest throughout
the urologic oncology community in utilizing focal therapy to mitigate such toxicities. The
rationale for focal therapy is based upon the recognition that whole gland treatment is
associated with unacceptable toxicity rates, while concurrently it is also realized that
patient morbidity and mortality is due to the progression of major foci of high-grade
disease, i.e. the index lesion.
Planning studies have shown that focal brachytherapy is feasible and results in significant
reductions of dose to critical structures. In a historic cohort of patients treated at Johns
Hopkins, the investigators have demonstrated that a modest reduction in dose results in
clinically meaningful reductions in urinary toxicity. Al-Qaiseh et al. found that focal plans
resulted in >50% reductions in dose to urethra and rectum. However, focal plans were highly
sensitive to seed positioning errors, and focal targeting made seed positioning more
critical. This highlights the key utility and importance of the investigators' iRUF system
(integrated Registered Fluoroscopy and Ultrasound) in delivering focal therapy.
The investigators have developed a system of true dynamic intraoperative dosimetry which
utilizes fluoroscopy for seed cloud reconstruction and fusion to transrectal ultrasound
imaging. The investigators previously confirmed this method in a pilot trial of 6 patients
with encouraging results. Further refinement of the system was followed by a Phase II
clinical trial of this integrated platform on a larger group of patients. The investigators
confirmed the primary endpoint to compare intraoperative dosimetric predicted values using
iRUF method vs standard ultrasound-based seed tracking. The iRUF Phase II cohort had
statistically significant improvements in prostate coverage parameters, as well as lower
rates of rectal doses exceeding prescribed tolerance limits when compared to a historical
group of patients. Importantly, there was no trend toward higher prostate V200 doses,
indicating that excellent coverage did not come at the expense of excessive dose within
prostate.
This study will test the combination of PSMA-imaging with iRUF dynamic dosimetry to treat
prostate cancer with a focal approach.
Inclusion Criteria:
- Adenocarcinoma of the prostate
- Performance Status < 2
- Clinical stages (not radiographic stage) T1c - T2a, Nx or N0, Mx or M0
- Gleason 6-7 cancer
- Prostate volume < 60 cc (if MRI and TRUS have conflicting values, then MRI value will
be utilized)
- International Prostate symptom score (IPSS) 20 or less
- Ability to undergo DCF-Pyl PSMA PET as part of pretreatment staging
- Signed study-specific consent form prior to registration
Exclusion Criteria:
- Prior history of pelvic radiation therapy
- Major medical or psychiatric illness which, in the investigator's opinion, would
prevent completion of treatment and would interfere with follow up.
- Implanted device or apparatus which obstruct visibility of the implanted sources on
fluoroscopy
- Metallic implants, claustrophobia not amenable to medication, or known
contraindications to undergoing MR scanning
- History of other malignancy diagnosed within the past 3 years
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