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A rare case of cerebral hemorrhage associated with intra-arterial infusion chemotherapy for advanced sphenoid sinus cancer


1 Department of Radiology, University of the Ryukyus Graduate School of Medical Science, Okinawa, Japan
2 Department of Otorhinolaryngology, University of the Ryukyus Graduate School of Medical Science, Okinawa, Japan

Correspondence Address:
Joichi Heianna,
Department of Radiology, University of the Ryukyus Graduate School of Medical Science, 207, Uehara, Nishihira-Cho, Okinawa
Japan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1444_16

 > Abstract 


Central nervous damage related to intra-arterial infusion chemotherapy (IAC) for head and neck cancer reported to date are cerebral infarction, transient ischemic attack, and neuropathy. There have been no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Authors report a case that underwent intra-arterial infusion chemoradiotherapy for advanced sphenoid sinus cancer which extended to the left cavernous sinus and cranium, subsequently suffered cerebral hemorrhage thought to have been caused by IAC. Treatment should be performed with greater caution when the head and neck cancer involves the cavernous sinus or cranium, as in the present case.

Keywords: Cerebral hemorrhage, complication, head and neck cancer, intra-arterial infusion chemotherapy



How to cite this URL:
Heianna J, Yamashita Y, Iraha Y, Murayama S. A rare case of cerebral hemorrhage associated with intra-arterial infusion chemotherapy for advanced sphenoid sinus cancer. J Can Res Ther [Epub ahead of print] [cited 2019 Oct 19]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=264214




 > Introduction Top


Intra-arterial infusion chemoradiotherapy (IACRT) is an extremely effective therapy for advanced head and neck cancer,[1],[2],[3] especially in cases where surgery is not feasible. However, central nervous system damage is one of the most serious intra-arterial infusion chemotherapy (IAC) – related complications. IAC-related central nervous system damage reported to date has been limited to cerebral infarction, transient ischemic attack (TIA), and neuropathy;[4],[5] there have been no reports of cerebral hemorrhage. The purpose of this case report is to infer the onset mechanism of cerebral hemorrhage as a rare complication of IAC for head and neck cancer and to present a situation in which the rare complication may occur.


 > Case Report Top


A 70-year-old woman, with no remarkable medical history or comorbidity, underwent magnetic resonance imaging (MRI) for a chief complaint of headache. MRI showed a neoplastic lesion based in the left sphenoid sinus and extending to the skull. The tumor extended to the left cavernous sinus and infiltrated the left internal carotid artery [Figure 1]a. Based on biopsy results, tumor was diagnosed pathologically as squamous cell carcinoma. Although positron emission tomography (PET) showed a high standardized uptake value in the primary tumor, there were no distant metastases to organs including lymph nodes on PET. She was diagnosed with sphenoid sinus carcinoma (clinical stage T4bN0M0). We judged that surgery would be difficult based on the image findings and chose IACRT as a treatment. Intensity-modulated radiation therapy (2 Gy/fraction) was started for the lesion, and IAC was provided at the same time. It was decided that IAC would be carried out every 4 weeks, and anticancer drugs used were nedaplatin (80 mg/m2) and docetaxel (60 mg/m2) according to the Maeda protocol.[6] We inserted a standard catheter (Head-hunter, 5 French; Terumo, Tokyo, Japan) through the right femoral artery using Seldinger's method and performed angiography of the bilateral carotid arteries first. Angiography of the right internal carotid artery showed no tumor stain. Since angiography of the right external carotid artery showed slight tumor stain, we decided not to perform IAC of the right external artery region. The left internal carotid angiography showed tumor invasion of the left carotid siphon. Moreover, the venous phase of left internal carotid angiography showed a stagnation of the left cavernous sinus and superficial middle cerebral vein [Figure 2]a and [Figure 2]b. Left external carotid angiography showed tumor stain and involvement of the left maxillary artery and left middle meningeal artery (MMA) [Figure 3]a. Selective angiography of a branch of the left MMA using a microcatheter (Tellus, 1.9 French; Asahi Intecc, Aichi, Japan) showed early filling of the draining vein from the tumor stain [Figure 3]b. We determined the dose of anticancer drugs, administrated at the left maxillary artery and branch of the left MMA, based on the size of the tumor stain area on angiography and the enhanced area on cone-beam computed tomography. Anticancer drugs were infused at a rate of 3.0 ml/min. The reflux of anticancer drugs was absent at an infusion. The first IAC was completed with no problem. Since some reduction in tumor size was seen on CT and MRI after the initial treatment, we decided to go ahead with the second IAC as planned. The patient received the second IAC 4 weeks after the initial treatment. We provided the same treatment to the patient as the first time, but the infusion rate was lowered by half (1.5 ml/min) because the patient complained of a headache during anticancer drug infusion the first time. The headache was relieved by lowering the infusion rate.
Figure 1: (a) Contrast magnetic resonance imaging T1-weighted image showed a strongly enhanced neoplastic lesion primarily at the left sphenoid sinus. (b) Magnetic resonance imaging T1-weighted image shows a high-intensity lesion (arrow) in the left temporal lobe right after second intra-arterial infusion chemotherapy

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Figure 2: (a) Venous phase of left internal carotid angiography shows congestion of the left cavernous sinus (arrow) and superficial middle cerebral vein (arrow head). (b) Delayed phase of left external carotid angiography shows venous congestive continuation (arrow and arrow head)

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Figure 3: (a) Delayed phase of left external carotid angiography shows tumor stain (arrow) consistent with the left sphenoid sinus lesion. (b) Selective angiography of a branch of the left middle meningeal artery shows an early filling of the draining vein (arrow)

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After the second IAC, MRI at radiotherapy dosage of 40 Gy showed a good reduction in the left sphenoidal tumor and the appearance of a structure with peri-structural edema on the left temporal lobe [Figure 1]b. A metastatic lesion was ruled out with respect to this structure because PET showed no accumulation of 2-fluoro [18F]-2-deoxy-d-glucose in the structure. The mass lesion with edema was diagnosed as a subcortical hemorrhage based on the image findings. The patient did not complain of any particular neurological abnormalities. We judged this subcortical hemorrhage to be a complication associated with IAC because it occurred after IAC.

We performed the remaining radiotherapy up to 70 Gy on schedule with conservative treatment for subcortical hemorrhage, without performing a third IAC. No neurologic abnormalities were found over the course of treatment, and the cerebral hemorrhage was not treated. The result of image evaluation after treatment was a complete response [Figure 4]a, and the subcortical hematoma was completely absorbed [Figure 4]b. Imaging studies including PET showed no recurrence 2 years later, and the patient is currently being followed up in the outpatient clinic.
Figure 4: (a) Contrast magnetic resonance imaging T1-weighted image performed 2 months after completion of treatment showed disappearance of the enhanced lesion at the left sphenoid sinus. (b) Magnetic resonance imaging T1-weighted image is not able to detect the suspected hematoma in the left temporal lobe 2 month after the treatment

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 > Discussion Top


Complications peculiar to IAC for head and neck cancer include catheter procedure-related complications (arterial dissection and artery narrowing), local angiopathy (groin hematoma), vascular occlusion, and central nervous damage, which is a particularly serious complication. The reported incidence of central nervous system damage is 1.8%–3.7%.[5],[7] Central nervous damage related to IAC for head and neck cancer reported to date are cerebral infarction, TIA, and neuropathy.[5],[7] A PubMed database search of the English literature revealed no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Because this case involved intracranial hemorrhage, it is unlikely to have been caused by a catheter-related complication or vascular occlusion in the external carotid artery regions. Our case was a patient who had no medical history and no comorbidity (e.g., hypertension and diabetes) in particular. Since cerebral hemorrhage occurred right after IAC, the authors thought it was more likely to have been an IAC-related complication.

Since this case is the first report of cerebral hemorrhage just after IAC for head and neck cancer, there are no articles in which the cause of cerebral hemorrhage onset after IAC has been mentioned in the literature. However, it seems to be very useful to refer to the onset mechanism of dural arteriovenous fistula (DAVF) causing venous infarction and cerebral hemorrhage as a result of venous hypertension and congestion.[8],[9] In this case, a left sphenoid sinus tumor invaded the left cavernous sinus and cranium. The venous phase of initial left internal carotid angiography showed a stagnation of the left cavernous sinus and left superficial middle cerebral vein. Although venous pressure was not actually measured in this case, the venous pressure near the cavernous sinus might have been higher than usual as a result of partial obstruction of the left cavernous sinus due to tumor exclusion and invasion. In addition, selective angiography of a branch of the left MMA showed a draining vein like a shunt based on the tumor stain. This early venous filling may have been the uncal vein as it was near the left side of the supra sella.[10] A part of the anticancer drugs infused into feeding arteries at a moderately high pressure during IAC seemed to flow into the uncal vein showing a shunt-like draining vein. In addition to higher venous hypertension than usual near the cavernous sinus, authors inferred that the effect of anticancer drugs flowing into the uncal vein led to venous hypertension in the uncal vein, and as a result, it might have caused cerebral hemorrhage due to venous reflux in the tip of the left temporal lobe. Unfortunately, the measurement of venous pressure and angiography after cerebral hemorrhage were not performed in this case, but the onset mechanism of cerebral hemorrhage, in this case, seems to be similar to that in DAVF.

IAC is an extremely effective therapy for head and neck cancer, which is not amenable to surgery. The ratio of central nervous system complications of IAC for head and neck cancer is not high, but we must avoid complications as much as possible, because they may be fatal, once they occur. When head and neck cancer involves the cavernous sinus or cranium, as in the present case, venous pressure elevation in the neighborhood due to venous occlusion may be present, and the effect of anticancer drugs flowing into the cavernous sinus through the shunt-like draining vein may lead to further local venous reflux. Therefore, it is important to consider switching to concurrent systemic chemoradiotherapy since further venous reflux may occur due to the effect of inflowing anticancer drugs when IAC is performed in such cases.

Statement of human and animal rights for this type of study formal consent is not required. This article does not contain any studies with human participants or animals performed by any of the authors.

The statement of informed consent was obtained from all individual participants included in the study.

Consent

Informed consent was obtained from all individual participants included in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgments

We are grateful to Keiichi Nishimaki, Chief of Neurosurgery, Akita Red Cross Hospital, and Satoshi Takahashi, Associate Professor of Radiology, Akita University School of Medicine, for their invaluable opinion in this case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Kerber CW, Wong WH, Howell SB, Hanchett K, Robbins KT. An organ-preserving selective arterial chemotherapy strategy for head and neck cancer. AJNR Am J Neuroradiol 1998;19:935-41.  Back to cited text no. 1
    
2.
Homma A, Onimaru R, Matsuura K, Robbins KT, Fujii M. Intra-arterial chemoradiotherapy for head and neck cancer. Jpn J Clin Oncol 2016;46:4-12.  Back to cited text no. 2
    
3.
Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Suzuki F, et al. Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. Br J Cancer 2013;109:2980-6.  Back to cited text no. 3
    
4.
Gelman M, Chakeres DW, Newton HB. Brain tumors: Complications of cerebral angiography accompanied by intraarterial chemotherapy. Radiology 1999;213:135-40.  Back to cited text no. 4
    
5.
Gemmete JJ. Complications associated with selective high-dose intraarterial cisplatin and concomitant radiation therapy for advanced head and neck cancer. J Vasc Interv Radiol 2003;14:743-8.  Back to cited text no. 5
    
6.
Maeda A, Toh S, Higaki Y, Tomita K. Super-selective intra-arterial infusion chemotherapy for oral cancer. Stomato Pharyngology 2003;15:345-51.  Back to cited text no. 6
    
7.
Robbins KT. The evolving role of combined modality therapy in head and neck cancer. Arch Otolaryngol Head Neck Surg 2000;126:265-9.  Back to cited text no. 7
    
8.
Brown RD Jr., Wiebers DO, Nichols DA. Intracranial dural arteriovenous fistulae: Angiographic predictors of intracranial hemorrhage and clinical outcome in nonsurgical patients. J Neurosurg 1994;81:531-8.  Back to cited text no. 8
    
9.
Miyamoto N, Naito I, Takatama S, Shimizu T, Iwai T, Shimaguchi H, et al. Clinical and angiographic characteristics of cavernous sinus dural arteriovenous fistulas manifesting as venous infarction and/or intracranial hemorrhage. Neuroradiology 2009;51:53-60.  Back to cited text no. 9
    
10.
Ide S, Kiyosue H, Tanoue S, Okahara M, Sagara Y, Hori Y, et al. Anatomical variations in termination of the uncal vein and its clinical implications in cavernous sinus dural arteriovenous fistulas. Neuroradiology 2014;56:661-8.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

 
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