Feasibility and effectiveness of palliative intensity-modulated radiotherapy for carotid sinus syndrome secondary to recurrent head and neck cancer
- 1 Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
- 2 Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Japan
- Correspondence to Dr Kentaro Wada; kw10181309@gmail.com
Abstract
A 74-year-old man presented with recurrent syncope 3 months after definitive surgery for hypopharyngeal cancer. The patient experienced dizziness and severe hypotension on the movement of the neck and head. CT revealed disease recurrence with masses encasing the left internal carotid artery. The patient was diagnosed with vasodepressor type of tumour-induced carotid sinus syndrome (tiCSS) and was referred for palliative intensity-modulated radiotherapy (IMRT). Ten days after the commencement of IMRT (25 Gy in five fractions), the symptoms of tiCSS improved, and there was no re-exacerbation of the symptoms till the patient died 56 days after the commencement of RT. Palliative IMRT was feasible and effective for recurrent malignant tiCSS. Given the fact that palliative IMRT is minimally invasive, this option could be widely adapted for patients with such poor general condition and prognosis.
Background
Carotid sinus syndrome (CSS) is a rare complex symptom occurring in 1% of all syncope cases,1 resulting from serious and sometimes lethal head and neck malignancy. Treatment of the underlying malignancy can resolve the symptoms of tumour-induced CSS (tiCSS).2–4 In patients with recurrence and with tiCSS who typically present with a poor general condition and prognosis, palliative RT, especially intensity-modulated radiotherapy (IMRT), plays a crucial role as surgery or chemotherapy is often intolerable. However, palliative RT might be avoided in some cases, due to toxicity concerns outweighing the benefits. A few studies have reported that palliative RT could be effective for such patients. Herein, we describe a case where IMRT improved the symptoms of malignant tiCSS, suggesting IMRT as a promising, minimally invasive treatment option for patients requiring palliative care.
Case presentation
A 74-year-old Japanese man presented with neck lymph node recurrence after 3 months of definitive surgery for advanced hypopharyngeal cancer and was referred to palliative RT for CSS. The patient presented with pharyngalgia as a primary tumour-related symptom and was diagnosed with cT4a (invasion of the hyoid bone) N2c squamous cell carcinoma of the hypopharynx, according to the eighth edition of the Union for International Cancer Control staging system (figure 1A).5 He underwent total hypopharyngolaryngectomy with bilateral lymph node dissection and reconstruction using the free jejunal flap. The left external carotid artery and the hypoglossal nerve were resected due to tumour invasion. The surgical margins were negative. His pathological stage was determined as pT4a (invasion of the thyroid cartilage, hyoid bone and thyroid gland) N3b (eight metastatic lymph nodes/48 resected lymph nodes; extranodal extension of right levels 2 and 4 and left level 2–4 lymph node metastasis). Adjuvant therapy was not administered because the patient experienced pneumothorax and abdominal abscess after surgery.
CT during (A) initial diagnosis of hypopharyngeal cancer and (B) nodal recurrence, showing soft tissue lesions surrounding the left carotid artery. The yellow circle and the light blue arrow indicate the gross tumour and carotid sinus, respectively.
Investigations
CT 3 months after the surgery showed new lesions, one of which encased the left cervical artery; there were no clinical signs of infection. We diagnosed node recurrence (figure 1B). Seven days after diagnosis, the patient experienced the first syncope with hypotension without other accompanying symptoms when his head was raised. Thereafter, whenever his neck and head were turned or raised, the patient experienced syncope with a severe decline (>50 mm Hg) in supine systolic blood pressure. Each episode lasted a few minutes, and bradycardia or asystole could not be detected in the 24-hour electrocardiographic assessment. His heart rate was 90–100 beats/min at all times. Amezinium methylsulfate treatment was initiated to control the hypotension but was ineffective. As the volume of masses in the neck increased every other week, recurrent syncopal episodes worsened. The patient was diagnosed with pure vasodepressor tiCCS due to compression or invasion of the carotid sinus.
Treatment
The patient was referred for palliative RT. Owing to his poor general health condition, including poor blood pressure management, palliative surgery and chemotherapy were considered inappropriate. Informed consent was obtained before the initiation of RT. Palliative IMRT was administered consecutively every weekday, consisting of 25 Gy delivered in five fractions to the lesions around the left cervical artery (figure 2). Two days of breaks, taken during the weekend, were included in the treatment course. An immobilisation mask was used to stabilise the neck area without causing syncopal episode, and the patient was transferred to the RT treatment machine using a sliding board.
CT with dose distribution of radiotherapy with 25 Gy in five fractions. The light blue arrow indicates the carotid sinus. The yellow, magenta, green and blue contours indicate the spinal cord, reconstructed jejunum, oral cavity and submandibular grand, respectively.
Outcome and follow-up
Ten days after the commencement of RT, he could tolerate head movement and sit without fainting or falling; blood pressure was also stabilised (figure 3). The volume of the masses had been slightly reduced at that point. The patient’s overall quality of life (QOL) improved, as seen by the improvement in the ability to sit and eat and to perform everyday tasks (eg, brushing teeth or face washing). Fifteen days after the commencement of RT, the patient was discharged. No RT-related toxicities were observed. Although the patient’s condition did not sufficiently improve to allow him to stand or walk without assistance, he had no further syncopal episode until he died 56 days after the commencement of RT.
Time course of systolic blood pressure and heart rate. The blue arrows indicate the day of radiotherapy (RT) with 25 Gy in five fractions. The blue circle indicates 10 days after the commencement of RT. The asterisk indicates the break in RT, taken during the weekend.
Discussion
The carotid sinus reflex serves as a regulatory mechanism that maintains blood pressure. Receptors of the reflex exist in the tunica adventitia of the carotid sinus, located just superior to the bifurcation of the carotid artery; they generate afferent impulses along the stretch of the arterial wall, which are then transmitted to the medulla by the glossopharyngeal nerve. The efferent fibres descent in the vagus and sympathetic adrenergic nerves cause cardiac inhibition or arterial vasodilatation.6 The nerve elsewhere in the reflex arc can result in hypersensitivity in the entire arc. CSS can be classified into three types: the cardioinhibitory type, which manifests as bradycardia or asystole; the vasodepressor type, which manifests as a decrease in systolic pressure >50 mm Hg without a change in the heart rate; and the mixed type.7 Although pacemakers and anticholinergic agents are effective in patients with cardioinhibitory CSS,7 they do not provide a clinical benefit in patients with tiCSS,4 who usually exhibit vasodepressor CSS.2 The treatment of vasodepressor CSS remains to be established. Therefore, RT, surgery and chemotherapy are currently the primary treatment option for patients with tiCSS.2–4
Definitive-intent RT (63–66 Gy in 33–35 fractions) was reported to be effective for new cases of malignant tiCSS.4 However, there are no reports that palliative RT could be effective for patients with recurrent tiCSS and poor general health condition. It could be due to the belief that RT toxicity, typically using three-dimensional conformal RT (3DCRT), would negate the improvement in QOL. The negative impact of IMRT on QOL (eg, dry mouth and oral mucositis) is milder than that of 3DCRT in patients with head and neck cancer.8 Palliative IMRT using intermediate dose (25 Gy in 5 fractions) was reported to be feasible for patients with malignant head and neck cancer,9 while palliative RT using high dose (40–50 Gy in 16 fractions) without IMRT showed high toxicity; severe mucositis has been reported in 63%–65% of patients, and 25%–45% required nutritional support,10 11 whereas IMRT with 25 Gy in 5 fractions resulted in severe yet short-term mucositis in only 7% of patients.9 The merits of using high-dose IMRT remain unclear; thus, intermediate doses of RT should be used in patients expected to have shortened survival. Even in patients who underwent previous definitive RT, reirradiation has been reported to be well tolerated.12 Carotid blowout syndrome, which is a lethal condition occurring in some cases of repeated RT, rarely occurred when the cumulative dose was lower than 130 Gy.13 Carotid sinus irradiation to depress the nerve endings was reported ineffective.14 Therefore, the use of RT should be limited to malignant tiCSS.
Surgical intervention can provide immediate, complete and permanent elimination of tiCSS15 and can be an optimal option for new cases of head and neck cancer or benign carotid tumour that is hard to control with RT and chemotherapy. Nerve resection can resolve CSS symptoms.16 However, it is too invasive for patients with recurrent malignancy and tiCSS. Chemotherapy, which is usually administered to patients with recurrence depending on their treatment history or general condition, may be effective for malignant tiCSS.3 17 For patients who can tolerate chemotherapy, we recommend sequential palliative RT with a washout period for chemotherapy.
Learning points
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Radiotherapy (RT), surgery and chemotherapy are currently the primary treatment option for tumour-induced carotid sinus syndrome (tiCSS).
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Palliative intensity-modulated radiotherapy using intermediate doses can be a feasible and effective minimally-invasive treatment option for patients with recurrent malignant tiCSS and a poor general health condition.
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Surgical intervention can be an option for new cases of head and neck cancer or benign carotid tumour that is difficult to manage with RT and chemotherapy.
Acknowledgments
I would like to thank Toshiki Ikawa, Masayasu Toratani, Naoyuki Kanayama and Masahiro Morimoto for useful discussions.
Footnotes
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Contributors KW wrote the manuscript with support from TH, YS and TT.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Next of kin consent obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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