Adenoid cystic carcinoma with malignant pleural effusion: a case report and review of therapeutic challenges in metastatic management

Introduction

Adenoid cystic carcinoma (ACC) is a rare cancer primarily affecting the head and neck region, often involving the salivary glands (1,2). Despite standard primary tumor excision, around 40–60% of patients experience distant metastasis within a decade (3,4), with the lungs being the most common site (5). Distant metastasis significantly contributes to the poor long-term survival of patients with ACC and can occur even in the absence of local recurrence (6,7). However, for distant metastasis, no treatment has been proven to offer a survival advantage over observation alone (7,8). Among various metastasis sites, pleural metastasis and malignant pleural effusion in ACC are particularly rare (9-11), with only a few case reports documented.

Here, we present a case of ACC with lung and pleura metastasis, complicated with malignant pleural effusion and dyspnea. Our goal was to alleviate the patient’s symptoms by reducing the size of the lung mass while minimizing the potential adverse effects of radiotherapy (RT). The technique of online adaptive RT (OART) has been used to treat thoracic tumors in previous literature, showing possible dosimetric advantages over the standard method (12). We employed a combination of OART and deep inspiration breath hold (DIBH), specifically using computed tomography (CT)-based breath-hold OART to treat the lung and pleura metastases comprehensively.

To our knowledge, this is the first report using CT-based breath-hold OART to treat pleura metastasis and malignant pleural effusion in ACC. We aim to share our experience in treating this rare condition and discuss potential treatment options. We present this article in accordance with the CARE reporting checklist (available at https://tro.amegroups.com/article/view/10.21037/tro-24-46/rc).

Case presentation

In 2022, a 62-year-old non-smoking gentleman presented with metastatic ACC manifesting as low back pain. He had a history of early-stage parotid gland ACC, initially treated with tumor excision in 2005. The patient remained disease-free until 2015, when a local recurrence was detected on a follow-up positron emission tomography (PET) scan, showing clinical stage of rcT2N0M0 [by 7th edition of the American Joint Committee on Cancer (AJCC) staging system]. He subsequently underwent another tumor excision followed by adjuvant RT. In 2019, multiple lung metastases were discovered. Systemic therapy with chemotherapy and cetuximab was initiated (13), but the disease continued to progress, leading to the initiation of pembrolizumab in August 2020 (14). However, the disease remained progressive, prompting trials of tegafur-uracil combined with cyclophosphamide (15,16). RT in combination with pembrolizumab was administered from February to May 2021. Axitinib was introduced in July 2021 (17). In August 2021, cell block fluid cytology revealed malignant cells, and a pleural biopsy confirmed metastatic ACC in August 2021. Due to newly-found malignant pleural effusion and pleura metastasis, axitinib was switched to trametinib in October 2021 (18). During the treatment course with axitinib and trametinib, the patient had stable condition and fair performance status.

In April 2022, the patient was referred to our clinic due to metastasis-related back pain, and palliative RT was administered to his lower thoracic spine, with the regimen of 30 Gy in 10 fractions. Following the palliative RT, his back pain resolved. Several months later, in July 2022, the patient returned to our clinic for the treatment of progressive chest tumors. CT revealed many non-cystic nodular lesions that seemed connected to each other with diffuse pleural thickening. Given the favorable response of his bone pain to previous palliative radiation, we decided to perform radiation to his right lung and right pleural metastatic lesions. The treatment volume was large, and to minimize the lung dose, the DIBH technique was applied. To increase the patient’s compliance and reduce the time/MU of each treatment session, we gave 2 Gy per fraction to 40 Gy, which resulted in a similar equivalent-dose conversions in 2 Gy (EQD2) with 37.5 Gy in 15 fractions (EQD2 =39.1 for alpha-beta ratio of 10) as used in a previous literature (9).

Since the treatment field was large and extensive, the internal target volume expansion would almost certainly include the whole lung in the treatment field. Tracking was not feasible either since the treatment field was not only too large but also expanded and shrunk during breathing, causing the field to deform constantly.

To mitigate potential adverse effects, OART was selected to reduce the normal lung dose. The treatment was performed with the breath-hold technique. For each treatment session, a cone-beam CT (CBCT) was performed. Based on the CBCT, replanning was done with the full-replanning Ethos system (Siemens Varien, Germany). A physicist performed a plan quality assurance, and then a physician would decide whether the treatment plan was acceptable before a treatment session was performed. The criteria of acceptance were a gamma passing rate of 3 mm/3%. The constraints used for treatment planning are listed in Table S1. Throughout the treatment course, planning target volume (PTV) V95 was maintained over 95% for each session. The mean lung dose was reduced from 9.63 Gy for the non-adapted plan to 9.27 Gy for the adapted plan, and the normal lung volume expanded approximately 200 mL at the end of the treatment course. Re-planning time was 30 minutes on average for each treatment session.

Over the course of 20 treatment fractions (one fraction per day, five days a week), the patient experienced a gradual improvement in dyspnea. Daily CBCT revealed a decrease in chest tumor burden and an increase in the right lung volume. Serial CBCT images during the RT course are shown in Figure 1, while the dose distributions for the first, interim, and final sessions are shown in Figure 2. After the RT course was completed, the patient’s shortness of breath progressively improved, accompanied by a reduction in chest wall pain and numbness. Follow-up chest CT after RT treatment revealed a decrease in the sum of right thorax lesion diameters (from 93 to 66 mm). The dose of morphine required for pain control decreased from 180 mg per day to 60 mg per day over a period of two months. Grade 1 radiation dermatitis over the chest wall was found according to CTCAE version 5.0, and no other adverse effects of RT were noted.

Figure 1 Serial chest CBCT scans during the RT treatment course. Representative CBCT scans from the first day until the last day of the treatment course are presented here. CBCT, cone-beam computed tomography; RT, radiotherapy.

Figure 2 Dose distribution of the first, tenth, and last sessions is presented here. The red arrows indicate one of the large pleural metastatic gross tumors, which could not be seen at the end of the RT treatment course. RT, radiotherapy.

Unfortunately, the patient experienced disease progression three months after completing RT. Follow-up chest CT revealed local progression in both hemithorax. In the right hemithorax, pleural lesions enlarged rapidly. In the left hemithorax, multiple new lesions were seen, and pleural effusion was found. CT images one month and three months after RT treatment are shown in Figure 3. He eventually passed away in January 2023 due to dyspnea and respiratory failure. Figure 4 illustrates the treatment course for his ACC.

Figure 3 Representative CT images demonstrating disease progression. The CT image on the left was obtained within one month after completion of RT (A), while the image on the right was obtained more than three months post-RT (B). Comparison of the two time points shows clear evidence of bilateral thoracic tumor progression. CT, computed tomography; RT, radiotherapy.

Figure 4 The patient was diagnosed with parotid gland ACC in 2005. Multiple lung metastases were noted in 2019, and he received regimens of systemic treatments. Palliative RT to the lower thoracic spine was given in April 2022, and palliative RT to the right chest was given in July 2022. ACC, adenoid cystic carcinoma; RT, radiotherapy.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the research ethics committee of China Medical University Hospital [CMUH106-REC3-119(CR-5)] and individual consent for this retrospective analysis was waived.

Discussion

ACC is characterized by a high propensity for perineural spread, local recurrence, and distant metastasis (6,9,19), with the lungs being the most common metastatic site (5,11,20). The disease primarily affects individuals in their fourth to sixth decades of life, with a slightly higher incidence in females (9,19). Prognostic factors include tumor stage, nodal status, histological grade, and patient age (10). Among patients with distant metastases, lung involvement is associated with a relatively better prognosis compared to metastases at other sites (5,9). Despite its slow tumor doubling time and insidious growth pattern, patients with distant metastases are often asymptomatic, yet long-term survival remains poor (8). Seok et al. retrospectively reviewed 188 patients with ACC and identified tumor size, perineural invasion, and local recurrence as risk factors for lung metastases (7).

Unfortunately, no treatment has consistently demonstrated a survival advantage over observation alone for distant metastases (7,8). Surgical resection and radiation therapy have shown potential for select cases with lung metastases. Franzese et al. compared stereotactic body radiation therapy (SBRT) with conventional RT and concluded that SBRT demonstrated improved local control, though without a significant survival benefit (21). Additionally, Li et al. described a case of ACC with pulmonary metastases, successfully managed with a combined approach of immunotherapy and low-dose RT targeting multiple lung lesions, resulting in a favorable short-term outcome (6).

Malignant pleural effusion is an uncommon manifestation of metastatic ACC, with no standardized treatment strategy due to its rarity (9-11). A literature review was conducted using PubMed and Google Scholar, from their earliest available records, with the following keywords: “adenoid cystic carcinoma”, “lung”, “pleural effusion”, “pleural”, and “metastasis”. A review of the literature revealed only four reported cases, treated with various modalities including thoracoscopy, chemotherapy, pleurodesis, and RT (Table 1). Outcomes were uniformly poor, with two patients succumbing within seven months and others achieving only transient symptom relief. Collectively, these cases underscore the poor prognosis associated with ACC-related pleural effusion.

In the current case, we treated a patient with lung and pleural metastases, including malignant pleural effusion, using CT-based breath-hold OART. To our knowledge, this approach has not been previously reported in the literature for ACC. While the treatment provided temporary symptom relief and imaging improvements, the patient ultimately succumbed to disease progression.

Findings from this case suggest that in patients with pleural metastases treated with OART, a conservative radiation dose may be considered when there is a substantial disease burden. Our findings, together with evidence from the literature, indicate that aggressive treatment is unlikely to provide meaningful benefit in terms of disease control.

Conclusions

This case and previous reports highlight the challenges of managing ACC with malignant pleural effusion. While aggressive treatments such as surgery, RT, and systemic therapies may offer short-term benefits, long-term outcomes remain dismal, with survival rarely exceeding one year. While exploring novel therapeutic approaches and combinations is warranted, a realistic assessment of the prognosis and a timely consideration of best supportive care should be prioritized for these patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tro.amegroups.com/article/view/10.21037/tro-24-46/rc

Peer Review File: Available at https://tro.amegroups.com/article/view/10.21037/tro-24-46/prf

Funding: The study was partly supported by the hospital’s grant (DMR-HHC-111-6).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-24-46/coif). J.A.L. serves as an unpaid editorial board member of Therapeutic Radiology and Oncology from October 2024 to December 2026. 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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the research ethics committee of China Medical University Hospital [CMUH106-REC3-119(CR-5)] and individual consent for this retrospective analysis was waived.

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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