A pilot study of diffusion-weighted MRI in patients undergoing neoadjuvant chemoradiation for pancreatic cancer

Kyle C Cuneo, Thomas L Chenevert, Edgar Ben-Josef, Mary U Feng, Joel K Greenson, Hero K Hussain, Diane M Simeone, Matthew J Schipper, Michelle A Anderson, Mark M Zalupski, Mahmoud Al-Hawary, Craig J Galban, Alnawaz Rehemtulla, Felix Y Feng, Theodore S Lawrence, Brian D Ross, Kyle C Cuneo, Thomas L Chenevert, Edgar Ben-Josef, Mary U Feng, Joel K Greenson, Hero K Hussain, Diane M Simeone, Matthew J Schipper, Michelle A Anderson, Mark M Zalupski, Mahmoud Al-Hawary, Craig J Galban, Alnawaz Rehemtulla, Felix Y Feng, Theodore S Lawrence, Brian D Ross

Abstract

Purpose: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation.

Methods: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response.

Results: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10(- 5) mm(2)/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10(- 5) mm(2)/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders.

Conclusions: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.

Figures

Figure 1
Figure 1
ADC maps obtained from patients on the study. The region of interest (tumor) is outlined. Representative tumors with a low (A, 119 x 10− 5 mm2/s) and high (B, 168 x 10− 5 mm2/s) mean ADC are shown.
Figure 2
Figure 2
Relationship between pretreatment mean tumor ADC and subsequent histopathologic response after chemoradiation therapy. The percentage of tumor cell destruction was converted from the grading system described by Evans DB et al. (19) to a numerical scale. Pearson correlation coefficient was calculated to describe the relationship between ADC and percent tumor cell destruction.
Figure 3
Figure 3
Pretreatment ADC histograms generated for each tumor with the corresponding amount of tumor cell destruction (percentage listed) seen after chemoradiation therapy and surgical resection. A shift towards a higher ADC value was associated with improved pathologic response to chemoradiation.
Figure 4
Figure 4
Comparison of pretreatment ADC and change in size on CT scan in patients showing a pathologic response (> 90% tumor cell destruction) and in nonresponding patients (> 10% viable tumor). Mean pretreatment tumor ADC was significantly higher in responding patients compared to nonresponding patients. Whereas, tumor size did not change on CT imaging after treatment with neoadjuvant chemoradiation.
Figure 5
Figure 5
One stainless steel and two nitinol (nickel titanium alloy) stents were placed in fixed diameter plastic cylinders to simulate a bile duct. Stents were scanned in a water phantom with T2 and diffusion weighted MRI sequences. High levels of artifact were seen in the diffusion sequence with the stainless steel stent but not with the nitinol containing stents.

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