Efficacy of Feraheme as Lymphatic Contrast Agent in Prostate Cancer

CIO included several featured abstracts, and we had the opportunity to talk in more detail with one of the authors.

DattoliAuthors: M.J. Dattoli, S.M. Bravo, D.M. Kaplon, M. Hayes, A. Osorio, P.M. Dycus, D. Bostwick, J.M. Kaminski

Why did you decide to study Feraheme (ferumoxytol), and what sets your study apart from what is already in the literature?

Dr. Dattoli: In recent years, there has been an unprecedented expansion in the field of nanomedicine for both diagnostics and therapeutics. Current standard-of-care diagnostics for prostate cancer staging typically includes computed tomography (CT) and bone scans, both of which are insufficient, leading to unacceptably high false-positive and false-negative rates, especially in high-risk and recurrent disease. Previous studies using nanoparticle Ferumoxtran-10 (Combidex) demonstrated substantially increased rates of detecting lymphatic dissemination when coupled with magnetic resonance imaging (MRI), although Combidex is currently a non-FDA–approved reagent. Ferumoxytol is an FDA-approved ferromagnetic reagent with lymphotropic biokinetics similar to Combidex, which led to our interest in the current analysis.

Can you briefly describe your findings?

Dr. Dattoli: As expected, coupling Feraheme with MRI resulted in a 96% predictive accuracy in a cohort of patients comprised entirely of high-risk disease with results comparable to previous studies using Combidex.

Tell me about something surprising you encountered while doing this research.

Dr. Dattoli: Resolution of focal lymph node metastasis down to 2 to 3 mm was established in patients undergoing nodal dissection, setting a new lower limit of resolution using any molecular or functional imaging currently available. Independent of this study, patients having recurrent disease and low PSAs (<1 ng/mL) have also benefited, with Feraheme detection of malignant lymph nodes down to 2 to 3 mm.

How might your findings eventually affect clinical practice?

Dr. Dattoli: CT scans and bone scans must be challenged as tools for staging in patients with high-risk and recurrent disease. The inherent problem is the increased cost associated with advanced MRI/Feraheme imaging. Meanwhile, this imaging coupled with Sodium Fluoride F-18 PET would arguably be the most accurate staging possible, although F-18 PET adds even further cost. 

However, this increased cost must be weighed against the poor staging  associated with standard methods, the latter potentially leading to inappropriate treatment and increased future costs. Results using other advanced diagnostics, especially PSMA-PET scans, are promising, although also at increased cost when compared with current standard diagnostic testing.

What future studies would you like to see take place?

Dr. Dattoli: In view of the absence of toxicities at Feraheme infusions of 6 mg/kg along with increased rate of lymph node detection when compared to currently used diagnostics, we look forward to others duplicating our results.

What are you hoping that attendees take away from your presentation?

Dr. Dattoli: The improved accuracy of staging using MRI/Feraheme imaging could have significant therapeutic implications allowing for individual tailoring of treatment in the setting of high-risk and recurrent prostate cancer, which is simply not possible with current staging methods. 

 

Read the full abstract below:

Purpose: Ferumoxytol (Feraheme) is a ferromagnetic nanoparticle with lymphotrophic biokinetics. Feraheme is delivered to lymph nodes via normal macrophages. Magnetic resonance imaging (MRI) suppresses normal lymph nodes containing Feraheme. The objective is to validate the agent’s safety and efficacy in determining lymph node positivity in prostate cancer (PCa).

Materials and Methods: A nonrandomized prospective evaluation of 178 consecutive PCa patients at high risk for prostate lymph node dissemination were enrolled between February 2013 and March 2015. All patients received intravenous (IV) Feraheme. A total of 177 patients received a ferumoxytol infusion of 6 mg/kg administered over 20 minutes. One patient received a 3-mg/kg infusion. T2 MEDIC and T2* sequence imaging of the abdomen and pelvis were performed approximately 24 hours after infusion. Images were reviewed by two board-certified radiologists with consensus interpretations. Readers were blinded to clinical and histopathology information (pre-MRI TNM stage, PSA or Gleason score). Lymph nodes were deemed abnormal if they did not suppress after Feraheme infusion (group 1, 94 patients). Lymph nodes were deemed suspicious for malignancy by MRI if suppressed by Feraheme and satisfied usual size criteria with high signal intensity on diffusion-weighted imaging and decreased apparent diffusion coefficient map values and morphologic features (group 2, 84 patients). Eighty-three group 1 patients had computed tomography (CT) biopsies (77 pelvis, 6 retroperitoneum); 11 patients had open pelvic lymph node dissection (PLND). A total of 382 lymph nodes were sampled. Seventy-six group 2 patients had CT biopsies (73 pelvis, 3 retroperitoneum); 9 patients had open PLND. A total of 340 lymph nodes were sampled. Rad-path correlation was performed. Resected lymph nodes were stained and reviewed by a single pathologist with no knowledge of MRI findings. The histopathology results for each lymph node were catalogued for subsequent comparison with MRI findings.

Results: Ninety group 1 patients (96%) had metastatic PCa; 4 patients (4%) were normal. Sixty-eight group 1 patients (77%) contained malignant lymph nodes not fulfilling usual imaging criteria for malignancy. Thirty-nine 2 of 30 www.theiomeeting.com group 2 patients demonstrated metastatic PCa; 46 patients (53%) were normal. One group 2 patient had an allergic reaction hives; infusion was ceased at 3 mg/kg, and the patient was treated to complete resolution of symptoms with 50 mg of IV Benadryl.

Conclusions: Feraheme can evaluate lymphatic dissemination of metastatic disease in patients with PCa, with a lower limit of resolution of focal lymph node metastases of 2 to 3 mm. Better resolution carries implications for therapeutic radiation planning in the setting of newly diagnosed or recurrent or metastatic prostate carcinoma. Toxicity was very acceptable at 6 mg/kg. Feraheme may play a significant role as a lymphatic contrast agent in the early dissemination of lymphatic metastatic disease.