Metastatic brachial plexopathy presenting as radiation-induced plexopathy in metastatic lung cancer: a case report and literature review

Introduction

Brachial plexopathy can have various causes, both traumatic and non-traumatic. When it occurs in cancer patients, it immediately requires further attention as it may result from local or metastatic disease. Furthermore, in cancer patients, brachial plexopathy can also be caused by prior treatment, with previous radiation therapy in the brachial plexus (BP) region being a well-documented cause. Although the symptoms and the clinical course of the plexopathy can often point toward the etiology, it is of utmost importance to establish a correct diagnosis as this will determine the subsequent management. Below, we present a case in which a thorough analysis of the medical record, and particularly the performance of a [¹⁸F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), proved crucial in converting a missed diagnosis into adequate palliative care. We present this case in accordance with the CARE reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0028/rc).

Case presentation

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of University Hospitals Leuven (No. S71006). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

We present the case of a 75-year-old man with a history of a squamous cell carcinoma of the upper left lobe, staged cT4N3M1c (retropectoral and internal mammary lymph nodes on the contralateral side) for which he was treated with four cycles of carboplatin-paclitaxel-pembrolizumab. Given a deep partial response, a consolidating radiotherapy treatment to a dose of 46.75 Gy in 17 fractions was delivered to the primary tumor and involved lymph nodes (isodose levels shown in Figure 1A, dose-volume histogram of the right BP shown in Figure 1B) followed by pembrolizumab in maintenance therapy. A single retrosternal lymph node recurrence (station 3A) on the right side a couple of months later was also successfully treated with radiotherapy to 46.75 Gy in 17 fractions, adding a negligible additional dose to the right BP of 1.34 Gy. After 2 years of maintenance treatment, a complete response on [¹⁸F]FDG-PET/CT was achieved and pembrolizumab was halted (shown in Figure 2). Two years later, the patient presented to his neurologist with progressive function loss of his right arm. Electromyography showed a right-sided superior trunk BP injury with complete paralysis of the muscles innervated by the plexus. Additional imaging with magnetic resonance imaging (MRI) showed no underlying injuries but revealed signs of denervation edema in the right rotator cuff. A radiation-induced etiology was initially suspected, with differential diagnoses including direct radiation damage to the BP or post-radiation fibrosis in the right upper pulmonary lobe. Given the low likelihood of functional recovery, management centered on symptomatic relief through duloxetine therapy and orthopedic support with a custom-fitted brace. Given the progressive nature of the paresis and persistent neuropathic pain, a careful review of the radiation treatment plan was performed, which showed that the right BP had received an equivalent dose in 2 Gy fractions (EQD2) of 54.48 Gy (α/β ratio =3 Gy). This dose remains well below the conventionally accepted threshold of 60–66 Gy EQD2 for the BP, at which the risk of developing radiation-induced brachial plexopathy (RIBP) is less than five percent (1,2). Thus, a [¹⁸F]FDG-PET/CT was performed to investigate the possibility of an underlying malignancy. The scan revealed intense hypermetabolic activity in an infiltrative lesion originating from the C4–C5 spinal nerve roots and extending into the right BP, highly suggestive of metastatic plexopathy (shown in Figure 3). No other [¹⁸F]FDG-avid lesions were detected. Using the images of the [¹⁸F]FDG-PET/CT for target delineation, a palliative irradiation of the right BP was performed up to a dose of 30 Gy in 10 fractions (shown in Figure 4). Ultimately, the cumulative dose to the right BP was 94.01 Gy EQD2, well below the tolerance of the BP for re-irradiation of 103 Gy EQD2 as described by Dibs et al. (3). Although function of the right arm did not recover, his pain scores rapidly dropped from VAS 10/10 to 2/10 and significantly improved his quality of life. Two months later, the patient presented at a follow-up consultation with hypoesthesia extending from the umbilical level to the upper thighs, while motor function remained intact. An already scheduled [¹⁸F]FDG-PET/CT scan revealed intramedullary spinal metastases at T7 and T9–10. A subsequent MRI of the entire spine confirmed these lesions and identified an additional intramedullary metastasis at C6. High-dose corticosteroid therapy was initiated, and all lesions were treated with palliative radiotherapy (PRT) to a total dose of 20 Gy in five fractions. This resulted in a marked and durable improvement in sensory function of the affected region within three weeks. Four months later, the patient developed recurrent sensory loss in the lower limbs. Imaging revealed a new intramedullary spinal metastasis at T2–3, for which a final course of PRT (20 Gy in 5 fractions) was administered. Three weeks after completion of this treatment, the patient presented to the emergency department with worsening sensory and motor deficits in the lower limbs. During hospitalization at the pneumology ward, a follow-up [¹⁸F]FDG-PET/CT demonstrated widespread progressive disease. Following a multidisciplinary discussion involving the patient, his treating pneumo-oncologist, and his family, the decision was made to transition to palliative home care. The patient passed away three weeks later.

Figure 1 Treatment plan with isodose lines and a dose volume histogram illustrating BP dose distribution. (A) Coronal image of the treatment plan which shows the tumor apically in the left upper lobe, the right BP in bold orange and the isodose levels. (B) Dose volume histogram of the right BP. BP, brachial plexus.

Figure 2 Maximum intensity projection image of the patient following 2 years of maintenance therapy with pembrolizumab. Discrete uptake in the left upper lobe was interpreted as post-radiotherapy inflammatory changes.

Figure 3 Coronal images, axial images and a maximum intensity projection image of the patient with a highly hypermetabolic mass (black arrows) affecting the spinal nerve roots C4–C5 and extending in a linear manner through the right brachial plexus to the retropectoral area.

Figure 4 Coronal view of the palliative radiotherapy plan delivered. The target volume encompasses the hypermetabolic part of the right brachial plexus and was treated with 30 Gy in 10 fractions.

Discussion

Metastatic brachial plexopathy (MBP) is a rare manifestation and often debilitating presentation of advanced systemic cancer with an estimated prevalence around 0.4% in cancer patients (4). Breast and lung cancer account for more than two thirds of the cases and although MBP usually occurs in the context of known disease, it may occasionally present as the primary clinical sign of occult malignancy (4-6). MBP can be caused by primary or secondary perineural spread (PS). Primary PS occurs when tumor cells utilize neural pathways as a low-resistance conduit to travel from the primary site to the BP. In contrast, secondary PS involves invasion of the BP from adjacent structures or secondary locations not typical of the primary pathology (7). Both mechanisms could have been at play in our patient as there was tumor adjacent to the right BP at initial cancer diagnosis and he developed intramedullary metastasis shortly after the diagnosis of the MBP. PS is a well-established negative prognostic factor in non-small cell lung cancer, as well as a multitude of other cancers (8-12). Following the detection of the intramedullary metastases, the patient’s prognosis became increasingly poor; current literature cites a median survival of 5 months for such cases (13).

Up to half of cancer patients require radiotherapy during their treatment, with lung and breast cancer being the leading cancer sites (14). If these patients develop brachial plexopathy later on, distinguishing between MBP and RIBP may be challenging. MRI remains the gold standard for diagnosing BP. Typical findings in MBP include nodular nerve thickening, increased T2 signal intensity, and thick or nodular peripheral enhancement after administration of gadolinium-based contrast agents, as well as mass-like fusiform nerve enlargement. In contrast, RIBP can usually be visualized with mild to moderate nerve enlargement, variable T2 signal intensity (which may appear hypo- or hyperintense), and the characteristic thin “tram-track” pattern of enhancement (4,15,16). Clinical presentation can also help to differentiate: MBP presents classically with severe pain early on, whereas RIBP typically presents with paresthesia and weakness, with pain developing only at a later stage (4,17-19). Despite these patterns, overlap is substantial and conventional MRI alone often fails to provide a definitive distinction (20). Given the vast implications of a correct diagnosis, [¹⁸F]FDG-PET/CT has emerged as an important complementary tool in this diagnostic challenge. Chandra et al. [2016] reviewed 11 patients with breast cancer referred to their center for suspicion of MBP (21). [¹⁸F]FDG-PET/CT was able to confirm MBP in nine patients and differentiate it from RIBP in the other two patients. Furthermore, [¹⁸F]FDG-PET/CT was able to demonstrate distant metastasis in five patients which helped guide their treatment. Not only does [¹⁸F]FDG-PET/CT help to differentiate between MBP and RIBP, it also helps guiding the treatment of MBP. In a small retrospective analysis of Im et al. [2024], where seven patients received PRT for MBP, [¹⁸F]FDG-PET/CT was used to help delineate the target for six patients (18). All patients experienced at least partial alleviation of their symptoms, with two patients even reporting complete pain resolution. Unfortunately, motor weakness progressed in all patients, with four developing motor impairments in additional limbs due to progressive disease. Neuropathic pain, as these patients with MPB experience, affects up to 40% of cancer patients and remains notoriously difficult to manage due to its complex and multifactorial etiology (22). As a fundamental component of palliative care, PRT plays a pivotal role in significantly enhancing the quality of life across a broad spectrum of metastatic disease, including both osseous and soft-tissue involvement (23). PRT is particularly effective when a neuropathic pain component is present. This is supported by a prospective observational study by Saito et al. [2018], which identified a neuropathic component as a significant predictor of overall pain reduction, reporting a hazard ratio of 1.50 (24). Higher radiotherapy doses have also been reported to have higher response rates (4,25). The radiotherapy strategy was adapted to the patient’s evolving prognosis in this case. Initially, the patient received 30 Gy in 10 fractions to the BP, a validated palliative regimen but generally reserved for patients with a more favorable prognosis to ensure durable local control (26). However, following the diagnosis of intramedullary metastasis, these lesions received 20 Gy in five fractions. This transition to a more hypofractionated schedule reflects a shift toward minimizing treatment burden in a more advanced disease state.

Given the rarity and initial vague symptoms, diagnosis of MBP is often delayed and can take up to 25 months from initial onset of symptoms (17). The importance of a timely and correct diagnosis is underscored by the fact that once the axons and supporting structures are injured, called neurotmesis, and function loss has settled in, recovery is very unlikely as was the case for our patient (27,28).

Conclusions

In conclusion, we present a case of atypical presentation of MBP where initial clinical symptoms and imaging were suggestive of RIBP but [¹⁸F]FDG-PET/CT was pivotal in achieving the right diagnosis and aiding in the palliative treatment. Given the long delay in diagnosis of MBP, the increased sensitivity of [¹⁸F]FDG-PET/CT for MBP and the high impact of irradiation of hypermetabolic plexus on symptom control, a low threshold for performing [¹⁸F]FDG-PET/CT should be adopted in patients in whom MBP or RIBP is suspected.

Acknowledgments

The authors used Google’s Gemini 3.0, an AI-assisted editing tool, to improve spelling, grammar, clarity, and readability during manuscript preparation. After using this tool, the authors carefully reviewed and edited the text and take full responsibility for the final content.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0028/rc

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0028/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0028/coif). The 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. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of University Hospitals Leuven (No. S71006). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

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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