Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

doi:10.1016/j.ijrobp.2010.10.032

International Journal of Radiation OncologyBiologyPhysics

Volume 82, Issue 1, 1 January 2012, Pages 159-166

https://doi.org/10.1016/j.ijrobp.2010.10.032 Get rights and content

Purpose

To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases.

Methods and Materials

In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests.

Results

Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r_s = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r_s = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r_s = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r_s = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm.

Conclusions

MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

Introduction

Colorectal cancer is one of the leading causes of cancer-related mortality in men and women each year (1). During follow-up, as many as 50% to 70% of patients diagnosed with colorectal cancer present liver involvement, which in half of these patients is the only site of recurrence (2).

Surgery is nowadays accepted as curative treatment option for colorectal liver metastases but the majority of patients are not eligible for resection because of technical or medical reasons (2). When resection is not possible, radiofrequency ablation (RFA) is currently the most widely used treatment method (3). However, the location of metastases close to the large vessels, the main bile ducts, or the gallbladder poses a problem for adequate delivery of RFA.

Over the past 20 years, stereotactic body radiation therapy (SBRT) has evolved as another local treatment option for primary and metastatic liver tumors. Local control rates have been increased by dose escalation protocols while acceptable levels of toxicity have been maintained 4, 5. Nevertheless, to further optimize the treatment, the definition of the target volume should be improved. It is agreed that in SBRT for liver metastases, a safety margin should be added to the tumor visible in computed tomography (CT) and/or magnetic resonance imaging (MRI) to compensate for residual respiratory tumor motion and setup inaccuracies. However, there is still debate about the need for an extra margin to compensate for microscopic extension (ME), and a range of margins between 0 and 10 mm have been described in the literature 4, 5, 6, 7, 8. Neither has it been decided whether pretreatment with chemotherapy might influence the ME of the metastases. Similarly, to precisely define the limits of the target volume, the correlation between macroscopic tumor dimensions visible in medical images and pathology should be evaluated. To our knowledge, literature reports on these subjects are scarce 9, 10, 11, 12.

The aims of this prospective study were to correlate pathology macroscopic tumor dimensions with MRI measurements and to establish the microscopic tumor extension in a cohort of 20 patients with colorectal liver metastases.

Section snippets

Study design

Candidates for this prospective cohort study were diagnosed with colorectal liver metastases, planned for surgery and eligible to undergo an MRI. Patients with an insufficient renal function or estimated creatinine clearance <50ml/min were excluded. In total, 20 colorectal liver metastases were estimated to be included in a period of approximately one year, 10 treated preoperatively with chemotherapy and 10 not. The study was approved by the Ethical Commission of Erasmus MC. Written informed

Study population

Between February 2009 and January 2010 we enrolled 16 patients with colorectal liver metastases. Three patients were excluded from the analyses; two because of the lack of specimen photographs, and one because of a too thick slicing of the specimen. Patient characteristics of the 13 remaining patients with 21 metastases are presented in Table 1. The chemotherapy regimen administered as treatment before surgery included oxaliplatin, capecitabine and bevacizumab.

For all 21 metastases preoperative

Discussion

SBRT applied to unresectable colorectal liver metastases has demonstrated a good local control rate (17). To further optimize the treatment, we designed this study to compare pathology macroscopic tumor dimensions with MRI measurements, and to establish the microscopic tumor extension. MRI volumes and effective radii correlated well with macroscopic pathology (correlation close to 1 for all sequences). However, mean MRI volumes and effective tumor radii were statistically significant enlarged

Conclusions

Our study demonstrated a good agreement between the tumor dimensions measured by MRI and the macroscopic pathology, suggesting that MRI can be used for accurate tumor delineation. However, ME found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

Acknowledgments

The authors thank Rob van Os, M.Sc., Anne van der Pool, M.D., Wouter Wunderink M.Sc., Paulette Prins, PhD, and Hans Joosten for their contributions.

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: Conflict of interest: none.

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Clinical InvestigationComparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Study design

Study population

Discussion

Conclusions

Acknowledgments

Surg Oncol

Eur J Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Phase I study of individualized stereotactic body radiotherapy of liver metastases

J Clin Oncol

Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases

J Clin Oncol

Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies

J Clin Oncol

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution Phase I-II study

Acta Oncol

Stereotactic radiotherapy of primary liver cancer and hepatic metastases

Acta Oncol

Comparison of liver metastases volumes on CT, MR and FDG PET imaging to pathological resection using deformable image registration [abstract]

Int J Radiat Oncol Biol Phys

Clinical Investigation
Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases