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Acquired unilateral alopecia after arterial infusion chemotherapy in a recurrent nasopharyngeal carcinoma

Abstract Background Intractable nasopharyngeal hemorrhage is a severe complication with high mortality rate in patients with radiation therapy (RT) for nasopharyngeal carcinoma (NPC) that requires emergency treatment. Quite a few of them combine with tumor recurrence. Treatment planning for these patients is extremely difficult for oncologists, and effective treatments are lacking. Case A 42‐year‐old man had a history of recurrent NPC that was treated with 2 cycles of chemoradiotherapies from 2017 to 2019. Five months after the second round of chemoradiotherapy, an episode of massive nasal bleeding occurred. As positron emission tomography (PET) scan revealed tumor recurrence in the left wall of nasopharynx, superselective embolization and subsequent intra‐arterial infusion (IA, 4 times of cisplatin 60 mg + fluorouracil 1.0 g) were performed to stop bleeding and achieve tumor control. To date, the disease‐free survival time has been over 1 year. No tumor recurrence or rebleeding is found except for alopecia on the left side. Conclusions Interventional radiology is important and effective in the treatment of recurrent NPC for both massive nasal bleeding and tumor control. However, the unique complication of unilateral alopecia should not be ignored.


| INTRODUCTION
Irradiation and reirradiation are the mainstay of curative therapies for NPC. However, they may lead to substantial severe complications, including fatal hemorrhage. In addition to radiation injury, tumor recurrence is believed to be a significant cause of this critical condition. [1][2][3] Treatments for these patients are lacking. Interventional radiology has been widely used in the treatment of massive nasal bleeding after chemoradiotherapy for NPC, and this technique is also an appropriate choice to safely achieve tumor control. However, it is seldom recommended. In this case, interventional radiology was used not only to stop bleeding but also to achieve tumor control. Finally, a satisfactory result is obtained.
Five months after the second round of chemoradiotherapy, an episode of massive nasal bleeding occurred after the patient contracted a cold. Despite performing anterior and posterior nasal packing, approximately 700 ml of blood was discharged from his mouth and nasal cavity within 24 h. Emergent angiography was performed.
A ruptured pseudoaneurysm was identified in the petrous portion (C2 segment) of the left internal carotid artery (ICA) where the artery was completely interrupted ( Figure 1). Fortunately, complete cessation of bleeding was successfully achieved with coil embolization.
Subsequently, a PET scan revealed local recurrence of the tumor in the left nasopharyngeal area (Figure 2). According to the consultation of our NPC multidisciplinary team, the patient was not amenable to palliative radiotherapy and surgery. Therefore, we arranged the IA as  (Figure 4). Interestingly, the patient complained of alopecia on the left side 1 month after the first IA ( Figure 5), which lasted for 12 months before his hair came to recover. As the alopecia was reversible and occurred on the same side, the IA procedure was performed on, we made a diagnosis of IA-related alopecia.

| DISCUSSION
Currently, radiation is widely used as the first-line treatment for NPC and greatly improves patient survival. Nevertheless, radiation also places patients at risk of radiation-induced adverse effects, the most fatal of which is massive nasal bleeding. 4,5 These recurrent NPCs with massive nasal bleeding are usually dangerous and critical. Their treatment is extremely difficult, and effective treatments are lacking. [6][7][8] Previous reports on these patients mainly focused on hemostasis strategies, few took notice of further tumor control, which was also crucial to these patients. 9,10 Interventional radiology has been demonstrated to be safe and effective in the treatment of massive nasal bleeding after radiotherapy for NPC. Furthermore, superselective IA chemotherapy is believed to be superior to intravenous injection because higher concentration and lower dose of chemotherapeutic agents can be delivered directly to the tumor site. By this means, systemic toxic reactions can be minimized, while antitumor effect can be maximized. Thus, interventional radiology is recommended by the NCCN for many solid tumors, such as hepatocellular carcinoma and colorectal cancer and melanoma.
Since NPC tends to localize and metastasize to regional lymph nodes without general metastases, this technique should be an appropriate choice to safely achieve better tumor control. 11 However, it was seldom suggested to these patients.
The performance status (PS) score of this patient was 3 because of extensive blood loss and severe infection. According to the NCCN, locoregional recurrent NPC with prior RT on the condition of PS score 3 was recommended to receive best supportive care plus palliative RT or palliative surgery. However, the consultation of oncologist and surgeon indicated that he was no longer eligible for RT and surgery. Therefore, we arranged IA right after the embolism of ICA, as the existing tumor was still life-threatening if the patient was treated only with best supportive care. To date, no signs of rebleeding or tumor recurrence have been found.
The main hemostasis strategies of interventional radiology were embolism and stenting. The major side effects are cerebral ischemia (approximately 10%-25%) depending on collateral blood flow. 12 Compared to ICA embolism, the side effects of IA in ECA have seldom been reported. In the present case, the only significant complication of IA was unilateral alopecia, and this unique alopecia was reversible.
In fact, there have been no previous reports of alopecia correlated with IA in ECAs found in PubMed.
It is well known that chemotherapy causes alopecia however, it is less well known that hair follicles are more strongly affected when the chemicals are infused directly into the external carotid artery. Furthermore, alopecia caused by chemical infusion into the external carotid chemical artery is unilateral. Therefore, warning patients of the risk of unilateral alopecia is necessary when IA into the external carotid artery is planned.
In summary, the technique of transcatheter IA in the ECA should be a promising method with acceptable side effects for relapsed NPCs with massive nasal bleeding and is worth further prospective studies to improve the quality of evidence.