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Multiparametric MRI for prediction of treatment response to neoadjuvant FOLFIRINOX therapy in borderline resectable or locally advanced pancreatic cancer

  • Hepatobiliary-Pancreas
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Abstract

Objectives

To identify multiparametric MRI biomarkers to predict the tumor response to neoadjuvant FOLFIRINOX therapy in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).

Methods

From May 2016 to March 2018, adult patients with BR or LA PDAC were prospectively enrolled in this study. They received eight cycles of FOLFIRINOX therapy and underwent multiparametric MRI twice (at baseline and after the second cycle). MRI evaluations included dynamic contrast-enhanced MRI, intravoxel incoherent motion diffusion-weighted imaging, and assessment of T2* relaxivity (R2*) and the change in T1 relaxivity (ΔR1, equilibrium phase R1 minus non-enhanced R1) of the tumors. Factors to predict the responders determined by the best overall response during FOLFIRINOX therapy and those to predict progression-free survival (PFS) and overall survival (OS) were evaluated using multivariable logistic regression and the Cox proportional hazard model.

Results

Forty-one patients (mean age, 60.3 years ± 9.3; 24 men) were included. Among the clinical and MRI factors, the baseline ΔR1 (adjusted odds ratio, 31.07; p = 0.008) was the only independent predictor for tumor response. The baseline ΔR1 was also an independent predictor for PFS (adjusted hazard ratio, 0.40; p = 0.033) along with R0 resection. The use of a cutoff ΔR1 value of ≥ 1.31 s-1 enabled prognostic stratification (median PFS, 16.0 months vs.10.0 months; p = 0.029; median OS, 34.9 months vs. 16.6 months; p = 0 .023, respectively).

Conclusions

The baseline tumor ΔR1 value may be useful to predict tumor response and survival in patients with BR or LA PDAC receiving FOLFIRINOX neoadjuvant therapy.

Key Points

• Baseline ΔR1 was an independent predictor for tumor response (adjusted odds ratio, 31.07; p = 0.008) and progression-free survival (adjusted hazard ratio, 0.40; p = 0.033) in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant FOLFIRINOX therapy.

• The criterion of baseline ΔR1 value ≥ 1.31 s -1 allowed for the prediction of favorable tumor response and survival outcome after neoadjuvant FOLFIRINOX therapy.

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Abbreviations

ADC:

Apparent diffusion coefficient

AUC:

Area under the receiver operating characteristic curve

BR:

Borderline resectable

CAIPIRINHA-VIBE:

Volume-interpolated breath-hold examination with controlled aliasing in parallel imaging results in higher acceleration

CI:

Confidence interval

CR:

Complete response

DCE:

Dynamic contrast-enhanced

D fast :

Fast diffusion coefficient

D slow :

Slow diffusion coefficient

f :

Perfusion fraction

HR:

Hazard ratio

iAUC:

Initial area under the curve in 60 s

ICC:

Intraclass correlation coefficient

IVIM-DWI:

Intravoxel incoherent motion diffusion-weighted imaging

k ep :

Rate constant between extracellular extravascular space and plasma

K trans :

Volume transfer coefficient

LA:

Locally advanced

OR:

Odds ratio

OS:

Overall survival

PD:

Progressive disease

PDAC:

Pancreatic ductal adenocarcinoma

PFS:

Progression-free survival

PR:

Partial response

R1:

T1 relaxivity

R2*:

T2* relaxivity

RECIST:

Response evaluation criteria in solid tumors

ROI:

Region-of-interest

SD:

Stable disease

TE:

Echo time

v e :

Fractional extracellular extravascular space volume

ΔR1:

Change in T1 relaxivity

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (No. 2020R1F1A1048826).

Author information

Author notes

  1. Ji Hun Kang

    Present address: Department of Radiology, Hanyang University College of Medicine, Hanyang University Guri Hospital, Guri-si, Gyeonggi-do, Republic of Korea

Authors and Affiliations

  1. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea

    Ji Hun Kang, Seung Soo Lee, Jin Hee Kim, Jae Ho Byun & Hyoung Jung Kim

  2. Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea

    Changhoon Yoo, Kyu-pyo Kim & Baek-Yeol Ryoo

  3. Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea

    Song Cheol Kim

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Correspondence to Seung Soo Lee.

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The scientific guarantor of this publication is Seung Soo Lee.

Conflict of Interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

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Written informed consent was obtained from all subjects (patients) in this study.

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Institutional Review Board approval was obtained.

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• Prospective

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• Performed at one institution

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Kang, J.H., Lee, S.S., Kim, J.H. et al. Multiparametric MRI for prediction of treatment response to neoadjuvant FOLFIRINOX therapy in borderline resectable or locally advanced pancreatic cancer. Eur Radiol 31, 864–874 (2021). https://doi.org/10.1007/s00330-020-07134-8

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  • DOI: https://doi.org/10.1007/s00330-020-07134-8

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