Palliative Radiotherapy for Multiple Liver Metastases of Merkel Cell Carcinoma: A Case Report

Abstract

Introduction

There have been few reports of the efficacy of palliative radiotherapy (RT) for liver metastases of Merkel cell carcinoma (MCC). A case of a patient with gastrointestinal symptoms and liver dysfunction caused by multiple liver metastases of MCC is presented. Palliative RT improved the symptoms and liver function, enabling the continuation of systemic therapy.

Case Presentation

A 66-year-old woman presented with metastatic MCC. Palliative RT (20 Gy in 5 fractions) was administered to the metastases extending from thoracic vertebra 11 to lumbar vertebra 1, and metastases in the left lobe of the liver were unintentionally partially included in the irradiation field. After palliative RT, avelumab therapy was initiated, but she complained of nausea and loss of appetite. Subsequent evaluations showed liver dysfunction and rapid progression of liver metastases. Palliative RT (20 Gy in 5 fractions) was administered to the right lobe of the liver, avoiding overlap with the previously irradiated area. Two weeks after RT, the patient showed significant improvement in the symptoms and liver function. The patient experienced no significant adverse events. She continued avelumab treatment, but she died 2 months after palliative RT to the right lobe of the liver due to progression of the MCC.

Conclusion

Palliative RT should be considered a treatment option for patients with MCC who develop symptomatic liver metastases.

Introduction

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. Risk factors include advanced age, immunodeficiency, and ultraviolet exposure, with a predilection for the head and neck region [1]. The prognosis of patients with MCC is generally poor, and treatment options are limited, particularly for metastatic disease. Radiotherapy (RT) has proven to be an effective treatment modality for MCC, and palliative RT should be considered for symptomatic relief in cases of metastatic MCC [2]. Recently, palliative RT to the liver has been of increasing interest in improving symptoms and liver function. A phase III study examining the efficacy of whole-liver RT (WLRT) in patients with hepatocellular carcinoma and liver metastases who were not eligible for systemic treatment reported that WLRT provided significantly better symptomatic relief than the best supportive care [3]. However, no cases of MCC were included in that trial, and there have been few reports of palliative RT for liver metastases of MCC.

Therefore, a case in which palliative RT of multiple liver metastases of MCC improved symptoms and liver function, leading to the continuation of systemic treatment, was presented to add to the evidence in this area. The authors have completed the CARE Checklist for this case report, which is attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547367).

Case Presentation

A 66-year-old woman with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was diagnosed with primary MCC of the left nasal wing in October 2022. She underwent total resection of the left nasal wing in November, followed by postoperative irradiation with 55 Gy in 22 fractions using a 6-MeV electron beam in December 2022. In October 2023, she developed recurrence with left neck lymph node metastases and received intensity-modulated RT with 66 Gy in 33 fractions, achieving a complete response. In March 2024, the patient developed recurrence with multiple liver metastases and multiple bone metastases. At that time, palliative RT with 20 Gy in 5 fractions was administered to the metastases extending from thoracic vertebra 11 to lumbar vertebra 1. Unintentionally, part of the left lobe of the liver was included in the irradiated field (Fig. 1). In the first week of April 2024, after the completion of palliative RT, avelumab treatment was started. However, by the third week of April, the patient developed nausea and loss of appetite. Further evaluations, including contrast-enhanced computed tomography, showed liver dysfunction and rapidly progressing liver metastases (Fig. 2a). Shrinkage of the metastases in the left lobe of the liver was noted at that time, which was considered to be due to the effect of palliative RT. In the fourth week of April, palliative RT with 20 Gy in 5 fractions was administered to the right lobe of the liver, ensuring no overlap with the previously irradiated field (Fig. 2b). One hour before each irradiation, granisetron 1 mg was given prophylactically. After 2 weeks of palliative liver RT, the patient showed marked improvement in nausea, loss of appetite, and liver function. Contrast-enhanced computed tomography 2 weeks after RT showed a good response to the metastases in the right lobe of the liver (Fig. 2c). The timeline of RT and changes in liver function are shown (Fig. 3). The patient experienced no significant adverse events after RT and continued avelumab therapy. However, avelumab treatment did not yield a sufficient therapeutic response. In the third week of May, further progression of systemic metastases was observed. Despite receiving palliative RT for liver metastases, the patient died in the fourth week of June 2024, 9 weeks after undergoing RT.

Fig. 1.

Palliative RT for thoracic vertebra 11 to lumbar vertebra 1, demonstrating the inclusion of the left hepatic lobe within the irradiation field.

Fig. 2.

a Contrast-enhanced abdominal computed tomography before RT. Multiple metastases in the right lobe of the liver are detected. b Palliative RT for multiple liver metastases with 20 Gy in 5 fractions. c Contrast-enhanced computed tomography 2 weeks after RT for multiple liver metastases.

Fig. 3.

Time courses of aspartate aminotransferase and alanine aminotransferase level changes.

Discussion

This case demonstrated two important issues. First, palliative RT for multiple liver metastases of MCC was effective in improving symptoms and liver function. Second, partial liver RT may result in improvements in liver function and symptoms.

Palliative RT for multiple liver metastases of MCC successfully improved symptoms and liver function. There are several reports describing WLRT as a modality for liver metastases. Retrospective analyses and phase II trials have reported symptom relief and improved liver function following WLRT with approximately 8–21 Gy for primary hepatocellular carcinoma or liver metastases, achieving symptom relief or liver function improvement in 52–100% of cases [4–6]. More recently, the results of a randomized, phase III trial investigating the utility of WLRT were published [3]. In this trial, patients with hepatocellular carcinoma or liver metastases were randomized to receive WLRT or supportive care, with the primary endpoint being pain relief. The results showed that the WLRT group achieved significantly greater pain relief than the control group (67% vs. 22%, p = 0.0042). Though this trial demonstrated the efficacy of palliative RT for the liver, the primary sites were mainly colorectal cancer, breast cancer, pancreatic cancer, and lung cancer; no cases of MCC were included. To the best of our knowledge, the only study of the efficacy of palliative WLRT for MCC was a short case letter by Andruska et al. [7]. Liver metastases occur in up to 43% of patients with primary head and neck MCC [8]. Thus, liver metastases of MCC are not uncommon in clinical practice, and it is important to consider strategies to manage this disease. The present case and the report by Andruska et al. [7] suggest that palliative RT for liver metastases of MCC is beneficial. Further studies are needed to validate the efficacy of palliative RT for liver metastases of MCC.

To avoid overlapping with the previous radiation field, partial liver RT was selected in the present case. Nevertheless, both symptomatic relief and improvement in liver function were achieved. Although WLRT is generally the standard approach for palliative treatment of liver metastases, this case demonstrates the potential benefit of partial irradiation under specific clinical circumstances. As reviewed by Pennock et al. [9], partial liver irradiation is a valid option for a group of patients with a poor prognosis. Most patients included in previous reports had hepatocellular carcinoma or liver metastases from colorectal cancer. There have been no prior reports of partial liver RT for liver metastases of MCC, and the present case may, therefore, provide new insights in this regard. Based on the clinical course of the present case, partial liver RT may be a viable treatment option when symptomatic or liver function-impairing metastatic lesions can be identified. In cases for which WLRT is not feasible, partial liver RT should be considered actively.

MCC is highly sensitive to treatment, and there is a risk of tumor lysis syndrome when the tumor volume is large. Although no apparent adverse events were observed in the present case, Dirix et al. [10] reported tumor lysis syndrome after chemotherapy for metastatic MCC. Therefore, further data accumulation and clinical trials are required to verify the safety and efficacy of liver RT.

The present study has some limitations. First, the observation period following the completion of liver RT was only 1 month, and long-term safety could not be assessed. Second, the liver RT in the present case was sequential, due to the progression of the disease, which is a different approach from the WLRT used in recent studies.

In conclusion, palliative RT for liver metastases of MCC effectively improved symptoms and liver function. For patients with symptomatic liver metastases of MCC, palliative liver RT should be considered a treatment option. Further studies are necessary to strengthen the evidence.

Acknowledgment

The authors would like to thank Forte Science Communications (https://www.forte-science.co.jp) for English language editing services.

Statement of Ethics

The Jichi Medical University Central Clinical Research Ethics Committee determined that our project does not meet the “Common Rule” definition of human subjects’ research and does not require a Certified Review Board review. Written informed consent was obtained from the patient prior to death for the publication of case details and accompanying images. Written informed consent was also obtained from the patient’s husband.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Nagamura Y. and Endo M. designed this study. Kado S. and Endo M. were involved in the patients’ management. Ogawa K., Takahashi S., Nakagawa M., Nakamura M, Fukuda Y., Kawahara M., and Akahane K. contributed to the data collection. Mori H. and Shirai K. supervised the project. All authors approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.