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Bladder Fiducial Markers and Diffusion-MRI to Optimize Bladder Chemo-Radiotherapy

Funder: National Cancer Institute

Funding period
USD 1.6 M
Funding amount
? DESCRIPTION (provided by applicant) PROJECT ABSTRACT : Management of localized muscle-invasive bladder cancer (MIBC) with radical cystectomy is associated with risk of significant morbidity, perioperative mortality, and decreased quality of life- especially among the growing number of elderly. A less invasive and morbid, but equally effective means of treatment is needed. Multi-modal treatment of MIBC (maximal trans-urethral resection, followed by combined chemo and radiotherapy) is, for well-selected patients, associated with survival outcomes comparable to cystectomy and lower morbidity and mortality, but also offers bladder preservation. However, in the U.S., multi-modal therapy is not common for 3 reasons: First, there is uncertainty among referring urologists as to whether all tumor is visible at time of resection. Second, no currently available radiographic technologies allow reliable visualization of the bladder tumor site and its margins. Furthermore, the bladder is a deformable, mobile structure, whose location, size and shape vary depending on bladder and bowel fullness. This makes it very possible that the whole bladder and tumor site are not consistently treated, and that collateral radiation occurs. Third, we lack a non-invasive (e.g. imaging-based) means by which to assess for local control after treatment. Emerging data suggests that multi-parametric diffusion- weighted and contrast enhanced MRI can detect occult disease, but this has not been robustly validated because imaging findings, to date, could not be definitively correlated with histology of the same bladder site. We describe a means to reliably mark the bladder margins and tumor site to resolve these limitations of multi-modal therapy. To date, no means of marking the bladder walls has proven effective and reliable. We developed a novel fiducial marker design and placement protocol, initially to simply improve targeting of the tumor-site with high-dose radiotherapy. These ultra-small 24K gold markers are placed endoscopically in submucosa around the tumor site at time of pre-treatment maximal resection, and, at the anatomic boundaries of the bladder, to optimize image-guided bladder radiotherapy. To date, we have placed our markers into 32 patients with MIBC at UCSF. They are visible with any imaging modality, including all on- table imaging. They are safe and easy to place, appear not to migrate, and are durable. We propose that our fiducial markers serve to increase high-dose radiotherapy targeting accuracy and lower collateral radiation. The goals of the work proposed here are to (1.) Assess the efficacy, treatment benefit, and generalizability of our markers and placement technique among a larger sample of patients with MIBC; 2. Use our fiducial markers to assess the degree to which urologists may miss occult tumor outside of the main resection area; and 3. Use our markers to assess the positive and negative predictive value (PPV, NPV) of diffusion-MRI to detect occult tumor pre and post-treatment. To accomplish these goals, we will perform 2 separate but complementary studies at UCSF--one in collaboration with Harvard/MGH.

USD 291.4 M
Aggregated funding amount
USD 716 K
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
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Defining NRF2 induced tumor invasion in bladder cancer

Bladder Cancer Advocacy Network to Yuki Kita, William Youngkwan Kim, Bernard Weissman

USD 50,000
2020 - 2021
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Alpha1H: A Unique Bladder Cancer Therapeutic, Acting with Great Precision

European Commission

USD 2,452,885
2020 - 2022
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer


USD 703,400
2020 - 2025
Project list item
SGLT-2 Inhibitors and Early Bladder Cancer Events: An International Multi-Centre Study

Canadian Institutes of Health Research to Elisabetta Patorno, Laurent Azoulay, Devin Abrahami, Lysanne Campeau, Blanaid Hicks, Robert William Platt, Sebastian Schneeweiss, Oriana Hoi Yun Yu

USD 88,269
2020 - 2022
Project list item
Implication of neutrophil extracellular traps in the efficacy of bladder-sparing therapy in muscle invasive bladder cancer

Canadian Institutes of Health Research to Wassim Kassouf, Ciriaco A. Piccirillo, Jonathan David Spicer

USD 138,878
2020 - 2025
Project list item
Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer

National Cancer Institute to HUI LI

USD 205,913
2020 - 2025
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Analysis of the effect of IDO inhibition on activation of the aryl hydrocarbon receptor pathway in bladder cancer

São Paulo Research Foundation to Humberto Dellê

2020 - 2021
Project list item
A new bladder cancer model based on tissue reprogramming and gene targeting

National Cancer Institute to FLAMINIA TALOS, DAIFENG WANG

USD 203,843
2020 - 2021
Project list item
Identification and analysis of early prognostic markers of bladder cancer using generated nanobodies

Russian Science Foundation to Sergei Tillib

2020 - 2022
Project list item
Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020
Project list item
Platform Selection for Biomarker Directed Radiotherapy for Bladder Cancer

NIHR Evaluation Trials and Studies Coordinating Centre to Catharine West

USD 51,871
2020 - 2020
Project list item
Chemotherapy plus PD-1 blockade as bladder-sparing treatment for muscle-invasive bladder cancer

V Foundation for Cancer Research to Matthew D Galsky

USD 600,000
2019 - 2022
Project list item
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

2019 - 2023
Project list item
Bladder cancer chemotherapy potentiation with a multiprong arachidonic acid pathway modulator

National Cancer Institute to PAUL THOMAS HENDERSON

USD 300,000
2019 - 2020
Project list item
Implementing Risk-aligned Bladder Cancer Surveillance

United States Department of Veterans Affairs to FLORIAN R SCHROECK

2019 - 2023
Project list item
[The association between SORL1 and advanced bladder cancer] - Original in Japanese

Japan Society for the Promotion of Science to Takanobu UTSUMI

USD 26,335
2019 - 2021
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