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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 1044-1049

Evaluation of computed tomography morphologic criteria in gastrointestinal tract hepatic metastases patients treated by chemotherapy


1 Department of Radiodiagnosis, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Radiodiagnosis, Ministry of Health, Menoufia, Egypt

Date of Submission27-Feb-2017
Date of Acceptance14-May-2017
Date of Web Publication31-Dec-2018

Correspondence Address:
Hanem A Metwally
Department of Radiodiagnosis, Ministry of Health, Berket El Sabaa, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_149_17

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  Abstract 


Objectives
The objective of this study was to evaluate morphologic and response evaluation criteria in solid tumors (RECIST) criteria in gastrointestinal tract (GIT) liver metastases patients as regards tumor marker and clinical response of patients.
Background
To evaluate morphological response criteria which detect tumor density changes on contrast enhanced computed tomography (CECT) in GIT liver metastases patients. These criteria will help to detect response to treatment by chemotherapy early before tumor size changes.
Patients and methods
We included in this study 40 patients already diagnosed with GIT liver metastases by physical examination, tumor marker assessment, and CECT. The patients received three to six cycles of chemotherapy followed by repeated physical examination, CECT, and tumor marker assessment. The lesions in the liver were then evaluated by RECIST and response criteria depending on morphology.
Results
There is a significant statistical relationship between morphological response and tumor marker response of patients (P = 0.002). However, the relationship between morphological response and clinical response is not statistically significant (P = 0.087). There is no significant statistical relationship between morphological response and RECIST (P = 0.281).
Conclusion
Morphologic criteria had significant statistical association with tumor marker response in patients with GIT liver metastases treated by different types of chemotherapy.

Keywords: contrast enhanced computed tomography, gastrointestinal tract cancer, hepatic metastases, morphologic criteria, response evaluation criteria in solid tumor


How to cite this article:
Mohammed HH, Abdullah MS, Alhanafy AM, Metwally HA. Evaluation of computed tomography morphologic criteria in gastrointestinal tract hepatic metastases patients treated by chemotherapy. Menoufia Med J 2018;31:1044-9

How to cite this URL:
Mohammed HH, Abdullah MS, Alhanafy AM, Metwally HA. Evaluation of computed tomography morphologic criteria in gastrointestinal tract hepatic metastases patients treated by chemotherapy. Menoufia Med J [serial online] 2018 [cited 2019 Feb 20];31:1044-9. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/1044/248723




  Introduction Top


The liver is considered the most common site of distant metastases from the gastrointestinal tract (GIT)[1]. There is limited survival in patients with GIT liver metastases if there is no treatment, with a median of 7.4–11 months[2].

Imaging has the main role in detecting response to treatment and survival after treatment in GIT hepatic metastases patients[3]. There have been advances in radiological imaging such as development of different imaging methods, functional imaging techniques, contrast media, and new response criteria of tumor because of the improvements in the treatment of GIT hepatic metastases[4].

Computed tomography (CT) is considered a common imaging method for hepatic imaging in evaluating hepatic metastases patients, among the different imaging modalities available[3].

The response to treatment by chemotherapy was usually detected by changes in tumor size, as known by the response evaluation criteria in solid tumors (RECIST)[5].

Different response criteria depending on tumor density changes on contrast enhanced computed tomography (CECT) was described in gastrointestinal stromal tumors. These changes were also detected in patients under systemic therapy for renal cell carcinoma or liver metastases of colorectal origin[5].

The response of tumor by morphological criteria and by RECIST was correlated with clinical response and survival of patients[6].

The aim of this study is to evaluate morphologic and RECIST criteria in GIT liver metastases patients as regards tumor marker and clinical response of patients.


  Patients and Methods Top


We included 40 patients with GIT liver metastases in this study. The study was performed between April 2015 and December 2016. The study was conducted in Menoufia University Hospital. The study was approved by Ethical Committee of Menoufia Faculty of Medicine, and informed consent was taken from each patient.

The patients were chosen for the study and reviewed against inclusion and exclusion criteria.

Inclusion criteria

GIT cancer patients having liver metastases (stage IV) by American Joint Committee on Cancer staging criteria who are candidates for chemotherapy were included in this study.

Exclusion criteria

The exclusion criteria were as follows:

  1. Patients with life expectancy less than 6 months
  2. Patients with liver metastasis smaller than 1 cm in diameter.


All patients underwent complete physical examination, baseline tumor markers CEA and CA19.9 in serum using Access 2 (Beckman Coulter, 250 South Kraemer Boulevard, Brea, CA, 92821-6232, United States) and CECT.

The patients were treated by chemotherapy (three to six cycles) followed by repeated physical examination, CECT, and tumor marker assessment. The hepatic lesions were then evaluated by RECIST criteria and morphological response criteria.

Contrast enhanced computed tomography imaging

Triphasic liver protocol following a noncontrast study of the liver or a single-phase technique was performed using Toshiba Alexion, Japan a multidetector row CT scanner with 16 detector rows. For the triphasic liver protocol, the patients were imaged using bolus tracking technique; the imaging begins when 110 HU is reached and then 60 s from the beginning of intravenous injection with a rate of 3–5 ml/s. The third scan obtained was 6–10 min after the start of injection. For the technique of single phase, the patients were imaged 60–70 s from the beginning of injection with a rate of 2–3 ml/s.

Response evaluation

The response to treatment by chemotherapy was evaluated by using morphological criteria, classifying each metastasis to one of three groups:

  1. Group 3 metastasis had a poorly defined interface between tumor and liver and heterogeneous attenuation
  2. Group 1 metastasis showed homogeneous attenuation with a thin, sharply defined tumor–liver interface
  3. Group 2 metastasis could not be classified morphologically as 3 or 1.


  4. The morphological response criteria were classified as follows:

    1. Optimal response if the lesion characteristics changed from group 3 or 2 to group 1
    2. Incomplete if the lesions characteristics changed from group 3 to group 2
    3. No response if the group did not show any change or increase in pattern.


In the patients who had multiple tumors, the morphologic criteria response was obtained by detecting the most common response seen in most of tumors.

The response by RECIST criteria was defined as follows:

  1. Complete response: if all tumors disappeared
  2. Partial response (PR): decrease in more than 30% in the sum of the longest diameter of the target tumor
  3. Progressive disease (PD): increase in more than 20% in the sum of the longest diameter of the target tumor
  4. Stable disease (SD): cannot be classified as complete response, PR, or PD.


Statistical analysis

Data were statistically described in terms of mean ± SD, median and range, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups was done using χ2-test. P values less than 0.05 were considered statistically significant. All statistical calculations were done using computer program statistical package for the social science (SPSS Inc., Chicago, Illinois, USA) release 15 for Microsoft Windows (2006).


  Results Top


The final study consisted of 40 patients. The patient's age ranged from 28 to 76 years, with a mean age of 57.55 years. There were 25 (62.5%) men and 15 (37.5%) women [Table 1].
Table 1: Baseline patient characteristics

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There is a significant statistical relationship between the response by RECIST and tumor marker response of patients post chemotherapy (P = 0.022) [Table 2].
Table 2: Correlation between response evaluation criteria in solid tumors response and tumor marker response of patients post chemotherapy

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There is a significant statistical relationship between morphological response and tumor marker response of patients (P = 0.002) [Table 3].
Table 3: Correlation between morphological response and tumor marker response of patients postchemotherapy

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There is a significant statistical relationship between the response by RECIST and clinical response (P = 0.043) [Table 4].
Table 4: Correlation between response evaluation criteria in solid tumors response and clinical response of patients postchemotherapy

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There is no significant statistical relationship between morphological response and clinical response (P = 0.087) [Table 5].
Table 5: Correlation between morphological response and clinical response of patients post chemotherapy

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The statistical relationship between morphological response and RECIST response is not significant, with no association between best morphologic response and RECIST response (P = 0.281) [Table 6] and [Figure 1],[Figure 2],[Figure 3],[Figure 4].
Table 6: Correlation between morphologic response and response evaluation criteria in solid tumors response

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Figure 1: Female patient aged 50 years old having pancreatic cancer with liver and lymph nodes (LN) metastases. Contrast enhanced computed tomography (CECT) before chemotherapy (a): multiple lesions (red arrows) are seen at both hepatic lobes of heterogeneous attenuation, with no peripheral rim of enhancement with partially defined tumor–liver interface (black arrow) (pattern 2); CECT after three cycles of Gemzar (b) shows that the lesions (blue arrow) increased in size but still of heterogeneous attenuation, with no peripheral rim of enhancement with partially defined tumor–liver interface (black arrow) (pattern 2).

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Figure 2: Male patient aged 56 years old having rectal cancer with liver metastases. Contrast enhanced computed tomography (CECT) before chemotherapy. (a) A single target lesion is seen at the left hepatic lobe (segment 3) (red arrow) showing mixed attenuation, with no peripheral rim of enhancement with partially defined tumor–liver interface (black arrow) (pattern 2); CECT after four cycles of Folfri. (b) The target lesion (blue arrow) had the same size and still had mixed attenuation with thin, partially defined tumor–liver interface (black arrow) and no peripheral rim of enhancement (pattern 2).

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Figure 3: Female patient aged 40 years old having cancer colon with liver metastases. Contrast enhanced computed tomography (CECT) before chemotherapy. (a) A single target lesion is seen at the right hepatic lobe (segment 6) (red arrow) showing homogenous attenuation, with no peripheral rim of enhancement with partially defined tumor–liver interface (black arrow) (pattern 2); CECT after three cycles of Folfox. (b) The target lesion (blue arrow) had the same size and had homogeneous attenuation with thin, well-defined tumor–liver interface (black arrow) and no peripheral rim of enhancement (pattern 1).

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Figure 4: Male patient aged 65 years old having cancer duodenum with liver metastases. Contrast enhanced computed tomography (CECT) before chemotherapy. (a) Two target lesions are seen at segment 2 (red arrow) and segment 4 (yellow arrow) showing heterogeneous attenuation, with thin peripheral rim of enhancement with ill-defined tumor–liver interface (black arrow) (pattern 3); CECT after three cycles of 5FU-Ca leucovorin. (b) The target lesions (blue arrow) decreased in size and had mixed attenuation with partially defined tumor–liver interface (black arrow) and resolution of peripheral rim of enhancement (pattern 2).

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  Discussion Top


GIT cancer is classified as the third one among most common cancers. In all, 20% of GIT cancer patients have hepatic metastases at the time of diagnosis[1]. The latest few years had advances in the management of metastatic GIT cancer, leading to a significant increase in overall survival for these patients[7].

Although survival and clinical results are the main indicators of the good effect of chemotherapy, alternative objective methods depending on imaging measurements are introduced to evaluate the treatment effect of anticancer agents[8].

Different approaches to measure the response to chemotherapy have been used, such as WHO criteria[9], the RECIST[10], and the revised RECIST guideline (version 1.1) to optimize the original criteria[11].

All of these criteria detect tumor size reduction following chemotherapy to evaluate the response[12]. With the appearance of new types of chemotherapy that cause inhibition of growth instead of tumor regression, limited response rates according to RECIST have been observed, although with improvement in survival[13].

Llovet et al.[14] used other criteria to measure response instead of RECIST in patients with hepatocellular carcinomas: the viable tumor only should be measured to detect response of target hepatic lesions – that is, the area of the tumor that shows enhancement during the arterial phase.

Choi[3] showed that in GIST patients treated with chemotherapy tumor size decrease is not the main indicator to evaluate the response rate.

Smith et al.[15] proposed the use of CT criteria depending on the attenuation and size of MASS (morphology, attenuation, size, and structure) criteria for the metastases from renal cell carcinoma.

In a previous study of 59 patients having liver metastases of colorectal origin treated by chemotherapy with (n = 30) or without (n = 29) bevacizumab, Chung et al.[16] found that using modified CT criteria (≥10% size decrease or ≥15% attenuation decrease) is better than using RECIST 1.1 criteria.

Chun et al.[6] described three patterns of morphologic response in hepatic metastases in 50 patients having liver metastases of colorectal origin. The authors found the correlation between the three patterns of morphologic response and the pathologic response is statistically significant.

In our study, 40 cases with GIT liver metastases were included to evaluate CT morphological and RECIST criteria correlating with clinical response and tumor marker response.

In this study, the studied group age ranged from 28 to 76 years, with a mean age of 57.55 years.

This is in agreement with the study by Greenberger et al.[17], which states that GIT cancer is a disease of older patients, with peak incidence in the seventh decade. However, the disease can occur at any age and may be seen in patients in their twenties and thirties. In addition, similar results were noticed by Nishioka et al.[18], where the median of their studied group age was 61.5 years (range, 28–83 years).

In our study, cases distributed according to sex was follows: 62.5% were male and 37.5% were female. This is similar to the result of the study by Chun et al.[6], in which the percentage of male patients (55%) was higher than that of the female patients (45%). Also, this was similar to the result of the study by Nishioka et al.[18], in which the percentage of male patients (57%) was higher than the percentage of female patients (43%).

In this study, the most common site for GIT tumor having hepatic metastases was the pancreas (47.5%), followed by the rectum (17.5%).

This is in agreement with the study by Halldórsdóttir et al.[19], which states thatin two-thirds of the cases of hepatic metastases of unknown origin the primary tumor was later discovered. Most of the primary tumors were cancers in the pancreas, lung, and colon/rectum.

In this study, multiple hepatic metastases (85%) were more than solitary liver metastases (15%).

This is similar to the result of the study by Chun et al.[6], in which the percentage of hepatic metastases that are multiple (95%) was more than solitary liver metastases (5%). Also, this was similar to the result of the study by Nishioka et al.[18], in which 65 (76%) patients had multiple hepatic metastases, and is in agreement with the study by Dietrich et al.[20], which states that most hepatic metastases are multiple. In only 10% of cases metastasis is solitary.

In the current study, hepatic with extrahepatic metastases (57.5%) was more than hepatic metastases only (42.5%).

This is in agreement with the study by Dietrich et al.[20], which states that most tumors that metastasize to the liver, such as lung and breast cancers, spread to other sites at the same time.

Different result was noticed by Chun et al.[6], where hepatic metastases (55%) were more than hepatic with extrahepatic metastases (45%). Also, different result was noticed in the study by Nishioka et al.[18], where 45% of patients had extrahepatic lesions.

This result occurred as cases in the studies by Chun et al.[6] and Nishioka et al.[18] were colorectal only, whereas our cases were heterogeneous and 47% of cases were of pancreatic origin with more aggressive nature.

In this study, the statistical relationship between RECIST and clinical response of patients is significant (P = 0.043), whereas the relationship between morphologic and clinical response of patients is not statistically significant (P = 0.087).

This is in disagreement with the study by Smith et al.[15], which states that the most accurate response for detecting patients with better clinical outcome was MASS Criteria.

This may be because of dependence of improvement of patients' symptoms (upper quadrant pain and other GIT symptoms such as nausea) on tumor size. Therefore, if tumor morphology criteria changed but size of the tumor was the same, symptoms may not improve.

In this study, there is a higher statistically significant relationship between morphologic response and tumor marker response of patients (P = 0.002) compared with that with RECIST response (P = 0.022).

This is in agreement with the result of Shindoh et al.[5], who stated that when comparing the two response criteria, the morphological and RECIST criteria, the morphological response was better than RECIST in predicting the pathologic response of lesions.

In this study, discordance occurs between the morphological response and RECIST response (P = 0.281).

This is in agreement with the result of Shindoh et al.[5], who stated that, when correlating between morphological and RECIST response, the optimal response in morphologic criteria was seen in 39% of patients with RECIST PR and 26% of patients with RECIST SD or PD (P = 0.06).

Also, this disagrees with the result of Nishioka et al.[18], who stated that the optimal morphological response was seen in 28% of the patients with PR according to RECIST and in 18% of the patients with SD or PD. There was no significant statistical relationship between the morphologic and RECIST response (P = 0.42).


  Conclusion Top


Morphologic changes, identifiable on single-phase and triphasic CECT, form the basis for the morphological response criteria and had a statistically significant association with tumor marker response in GIT liver metastases patients receiving chemotherapy and need to be incorporated to treatment evaluation.

The occurrence of discordance between morphologic and RECIST-based responses indicates that both evaluation methods need to be implemented.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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