Fibrotic Response to Neoadjuvant Therapy Predicts Survival in Pancreatic Cancer and Is Measurable with Collagen-Targeted Molecular MRI.
Clin Cancer Res
; 26(18): 5007-5018, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32611647
ABSTRACT
PURPOSE:
To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC. EXPERIMENTALDESIGN:
Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101.RESULTS:
In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (-) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P < 0.05) and increased tumor fibrosis by collagen staining (P < 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging.CONCLUSIONS:
In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Páncreas
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Neoplasias Pancreáticas
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Terapia Neoadyuvante
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Carcinoma Ductal Pancreático
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Quimioradioterapia Adyuvante
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Recurrencia Local de Neoplasia
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Año:
2020
Tipo del documento:
Article