Assessing the value of computed tomography (CT) of the chest in the follow-up of patients with intrahepatic cholangiocarcinoma

Introduction

Cholangiocarcinoma (CCA) can be categorized into three categories based on its anatomical origin; intrahepatic, perihilar and distal with the last two types can be referred to as extrahepatic CCA. Accounting for less than 3% of all gastrointestinal cancers, the incidence of CCA in the United States is estimated to be 1.26 per 100,000 people per year with two-thirds being intrahepatic [Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2015] (1-3).

Multiple imaging modalities have a pivotal role in CCA management. Computed tomography (CT) is routinely used as the standard of care, due to its high accuracy in providing anatomical information and comprehensive evaluation. It can also detect any possibility of tumor metastases to the chest, abdomen or distant organs (4). Post-resection follow-up typically includes CT examinations of the chest, abdomen and pelvis are performed to evaluate for metastatic disease. The value of imaging the abdomen is required to evaluate for local disease. The added value of the CT chest and pelvis in the management of the post-operative surveillance of intrahepatic cholangiocarcinoma (IHCCA) has not been reported.

There are prior publications evaluating the added value of CT pelvis in patients with hepatocellular carcinoma (HCC) and pancreatic cancer (5-7). These have reported low added value. Adding additional imaging for surveillance without added value results in higher health care cost, radiologist fatigue, and unnecessary radiation exposure (8). In addition, although CT chest abdomen and pelvis can be at the same session, each one of them is a separate exam with its own current procedural terminology (CPT) which translates to higher cost when the three are performed.

Our initial observations were that when progression of disease was detected in the chest portion of the exam, there was also corresponding progression of disease in the abdomen portion of the exam in patients with IHCCA. Our hypothesis is that there is little added value of the short interval CT chest examination in the detection of progression of metastatic disease in the post-operative follow-up of patients with IHCCA. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-365/rc).

Methods

Patient population

This retrospective study was approved by the Institutional Review Board of University of Texas MD Anderson Cancer Center (No. 2020-0540), and informed consent was waived because of the retrospective nature of the study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The accessed data were collected from the Epic electronic health record system at The University of Texas MD Anderson Cancer Center in accordance with appropriate data protection and privacy regulations. The electronic health record board was searched to identify patients diagnosed with IHCCA from October 2010 through August 2020 for the following terms: cholangiocarcinoma, CT, and surgery. Selection criteria included patients that had a liver resection for IHCCA, had a CT examination of the chest, abdomen, and pelvis, and at least one follow-up post-operative exam within 6 months post-resection. The demographic, clinical and radiologic data were reviewed and collected for the analysis. Most CCA patients do not undergo surgery because they present with advanced disease, we only selected patients that were eligible for surgery.

Imaging techniques

General Electric (GE) Healthcare (Wisconsin, USA) and Siemens Healthineers (Erlangen, Germany) multi-detector CT scanners were used for imaging of the enrolled patients. All patients had a liver protocol imaging: this consisted of non-contrast abdominal CT scan images of the abdomen and pelvis were acquired at the late arterial and portal venous phase (60–70 seconds after contrast administration). The protocol also included 3 minutes after contrast administration imagining of the abdomen and pelvis. CT images of the chest were obtained in combination with the CT abdomen pelvis exam. The chest CT protocol for staging and follow-up imaging in IHCCA patients includes the following specifications: a tube voltage of 120 kVp is used, with intravenous contrast administered at a dose of 1.5 mL/kg of body weight using iodinated contrast material. The pitch is set between 0.8 and 1.2, depending on patient size and the specific scanner. Images are reconstructed with a slice thickness of 1 mm. Scans are typically performed during the venous phase (approximately 60–70 seconds after contrast injection).

Data collection and categorization

The first exam following liver resection was considered the baseline exam. Radiological reports of the baseline and follow-up imaging were reviewed and relevant data about disease status were collected. All imaging studies were interpreted by board-certified radiologists from MD Anderson Cancer Center, certified by the American Board of Radiology (ABR). These radiologists have specialized training in diagnostic imaging, ensuring high standards of accuracy and reliability in the interpretation of imaging results. On post-operative baseline and follow-up scans, metastatic disease involvement was classified as present in one or more of the three of the following: intrathoracic metastasis only, combined intra-thoracic and intraabdominal metastasis, intra-abdominal metastases without intrathoracic involvement.

Statistical analysis

Descriptive statistics were used to summarize patient characteristics. Continuous variables were reported as mean ± standard deviation, and categorical variables as frequencies and percentages. The primary outcomes were prevalence of isolated intrathoracic metastasis at baseline and the new isolated intrathoracic metastasis during follow-up. All analyses were performed using JMP statistical software (SAS Institute Inc., Cary, NC, USA). No formal hypothesis testing was conducted.

Results

Patient demographics

Our primary database search identified 111 patients that met our initial eligibility criteria. Eleven patients were excluded due to missing follow-up CT chest imaging, and 13 patients were excluded because of multicentric primary malignancy of different types. Thus, we included 87 patients (46 female and 41 male) in this study (Figure 1). The mean age at diagnosis was 59 years (standard deviation, 12 years).

Figure 1 Patient selection flowchart. CT, computed tomography.

The baseline clinicopathological data are summarized in (Table 1). A total of 87 patients were included in the study. The mean age at diagnosis was 59.14±12.4 years, with a nearly equal gender distribution. Most patients (86.21%) underwent hepatectomy, and the mean tumor size was 7.4±2.9 cm. Surgical margins were negative in 73.56% of cases, and all patients received adjuvant chemotherapy. Missing data was due to unavailability of certain details.

At baseline post-operative assessment (Table 2, Figure 2), the study population of 87 patients with surgically resected IHCCA was assessed for metastatic patterns. The results show that only 2 patients (2.3%) had isolated intra-thoracic (lung-only) metastasis, supporting the hypothesis that lung metastases alone are rare in this patient group. A larger proportion of patients, 15 (17.24%), had combined intra-thoracic and intra-abdominal metastases, while 21 patients (24.14%) had abdominal metastases without lung involvement. Importantly, many patients, 49 (56.32%), had no detectable metastases at baseline.

Figure 2 Flowchart of metastatic progression in patients with surgically resected intrahepatic cholangiocarcinoma.

During follow-up (Table 3, Figure 2), the metastatic patterns were reassessed. Follow-up studies time ranged from 25 to 77 weeks with a mean 39 weeks. Only 4 new cases (4.60%) of isolated intra-thoracic metastases were detected, further supporting the low prevalence of lung-only metastasis. Additionally, the 2 patients (2.30%) who initially had lung-only metastasis developed new intra-abdominal deposits, indicating progression beyond the lungs. Most of patients with metastases had combined intra-thoracic and intra-abdominal involvement (52 patients, 59.77%), while 16 patients (18.4%) had abdominal metastases without lung involvement at follow-up. Notably, 13 patients (14.94%) continued to have no detectable metastases during follow-up.

Discussion

The incidence rate of IHCCA rate an increasing over the past years; however, this is still a rare disease that occurs in 1.49 per 100,000 individuals in the U.S. (9). Recurrence rate after surgery in IHCCA patients according to Portolan et al. was 35.2% and of these recurrence cases, only 10% were to the chest (10). Most IHCCA patients are not eligible for surgery because they present with advanced disease from the beginning, but here we are only talking about patients that were eligible for surgery and removal of the tumor.

Our hypothesis was that there is little added value of the CT Chest examination in the detection of progression of metastatic disease to the chest in the post-operative follow-up of patients with IHCCA.

Based on National Comprehensive Cancer Network (NCCN) guidelines, version 1, 2022, there is no data to support surveillance protocol or tests for CCA; however, they recommended a careful discussion with every patient and a visit with 6-month interval over the first 2 years of treatment, then annually for the following 5 years (11). The European Society for Medical Oncology guidelines, recommended a follow-up of CCA to be done by full lab, tumor markers and CT chest, abdomen, and pelvis with 3 months interval for the first 2 years after successful treatment, that can be extended later to 6 months interval over the following 5 years (12).

In a study, the recurrence in the lung (pulmonary metastasis) was found in 6.6% among all resected patients and 11.3% among those with recurrent disease, accounting for 9.9% of the sites of initial recurrence (13). Rea et al. have conducted a study to compare liver transplantation after neoadjuvant therapy to resection as a treatment of CCA, the incidence of recurrence was found to be more localized at the abdomen in the resection group, however, for the post-transplant group the recurrence was more at distant site (14). In another study, tumor recurrence was seen locally even after liver transplant (15). According to multi-institutional database analysis study 933 patients were included. The rate of recurrence after surgical resection of CCA was estimated to be 73%, from this group 59.3% had only intrahepatic recurrence, 27% had intrahepatic and extrahepatic disease and, 13% had extrahepatic disease only, (lung, lymph nodes and peritoneum). Lung recurrence was mentioned as the most common of those 3 sites with around 29.8% of these cases with extrahepatic recurrence (16).

To the best of our knowledge, no prior study has evaluated the benefit of chest CT in follow-up investigations of patients with IHCCA. The outcome of our study confirmed our hypothesis that short interval chest CT is of limited benefit in the follow-up of IHCCA patients. Only 4.6% of our included patients had findings corresponding with disease progression in the chest without any progression intra or extra-hepatic on follow-up CT.

According to Zhang et al., the median age of recurrence was 61 years compared to our study which was 59 years, and the rate of disease recurrence after surgical resection can be as high as 71% which is close to our study which had recurrence rate around 85% either intra or extrahepatic (16). In addition, on follow-up exams the chest metastasis in our study was found to be around 28% which is comparable to most of these studies that ranged from (23.7% to 29.8%) (16,17).

Limitations to our study includes: small sample size given that the disease is rare as well as large missing clinic pathological data, and reliance on original radiology reports without secondary review. However, radiology reports data approximate the clinical practice and physician decisions. Clinical disease stage, tumor burden, or tumor size were not taken as factors as we studied the patient population. It may seem logical to consider that advanced stage and increased tumor burden at baseline may result in higher incidence of disease progression. However, we expect to see this progression as abdomen metastasis and not chest-only disease progression. Finally, most of our patient population had a relatively high tumor burden at time of diagnosis. Applying these results to a larger sample size with less tumor burden, we anticipate a lower incidence of chest-only progression.

Conclusions

The results of this study suggest that short-interval follow-up chest CT has limited benefit in surgically resected IHCCA patients with negative follow-up CT abdomen and pelvis for metastatic deposits as it is proven that it is rare to develop disease progression in the chest without corresponding disease progression in the abdomen. This study contributes to the ongoing discussion about optimizing follow-up protocols for IHCCA patients, potentially reducing unnecessary imaging and associated costs.

Acknowledgments

Funding: This work was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-365/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-365/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-365/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-365/coif). M.J. serves as an unpaid editorial board member of Journal of Gastrointestinal Oncology from January 2023 to December 2024. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This retrospective study was approved by the Institutional Review Board of University of Texas MD Anderson Cancer Center (No. 2020-0540), and informed consent was waived because of the retrospective nature of the study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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