Cervical Stabilization in Patients with Instability Resulting from Osteoradionecrosis with Subsequent Spondylodiscitis After Radiotherapeutic Treatment for Head- and Neck Carcinoma

Abstract

High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.

Introduction/Background

Radiotherapy, with or without systemic treatment is an important part of the treatment for locally advanced head and neck cancers. Despite recent advances in treatment more than half of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) develop a loco regional recurrence [1]. Unfortunately, loco regional relapses, and second primary tumours after definitive radiation treatment often occur within high-dose treatment volumes. Surgery is the first choice of treatment for secondary primaries or recurrent disease [2]. In case of inadequate margins postoperative reirradiation is indicated and if surgery is not feasible, primary re-irradiation can be considered [1].

Radiation has side effects in normal tissues due to homeostatic and metabolic cellular deficiencies due to hypoxia, hypo cellularity and hypo vascularity. This process may lead to tissue damage, fibrosis and delayed healing, subsequently causing an increased risk of infection [3, 4]. The severity of the acute and delayed damage caused by radiotherapy is related to total dose, dose per fraction and fractionation schedule [5]. Although the damage caused by radiotherapy will decline in time, the tissues involved are never fully recovered. High dose re-irradiation with curative intent, will lead to a higher morbidity.

One of the serious adverse events of high radiation dose in bone is osteoradionecrosis (ORN). ORN is a condition characterized by devascularized, devitalized or necrotic bone caused by irradiation-induced tissue changes. Pathogens enter the bone structures easier because of weakened tissue boundaries and will survive due to the declined defence mechanisms. Infections will weaken the bone even more and subsequent instability may occur [3, 6, 7]. According to the literature, the risk on ORN will increase with doses exceeding 60 Gray (Gy) [8–10]. Due to the increased risk of infection in ORN, secondary osteomyelitis may occur [3, 6]. This infectious disease is known as complication in the mandible, but is rarely described in the cervical spine [4, 11, 12]. If ORN and subsequent infections occur in the cervical spine, it may cause cervical instability or spinal cord compression with debilitating neurological function loss, requiring immediate surgical decompression of the spinal cord and stabilization of the cervical spine [3, 11].

We will discuss the treatment in four cases of radiation induced ORN with secondary spondylodiscitis and cervical instability.

Case series

Patient 1: (Neopharyngeal Ulceration)

The first case is a 72-years old male, who presented at the otolaryngology department with progressive pain in the neck, referred pain and swallowing disorders, progressive cervical kyphosis and bilateral upper extremity paraesthesias.

Thirteen years earlier he was diagnosed with T2N0M0 laryngeal cancer, initially treated with radiotherapy, but because of residual disease a laryngectomy was performed. Postoperatively, he developed a long lasting pharyngo-cutaneous fistula, which was finally closed by a pendicular myocutaneous pectoralis major flap.

Twelve years later a T3N2cM0 oropharyngeal cancer, located in the mid portion of the base of the tongue, was diagnosed. For functional reasons we chose for a combination of irradiation and surgery, because excision of the tumour at the base of the tongue would imply a total glossectomy. The tongue and both sides of the neck received 46 Gy external radiation, followed by a bilateral modified radical neck dissection and 24 Gy brachytherapy at the base of the tongue. Soon after finishing radiotherapy, he developed a submental ulcer and an ulcer at the posterior pharyngeal wall. Computed tomography (CT) scan of the neck showed a cervical osteomyelitis of C4–7, which was confirmed by magnetic resonance imaging (MRI) and Positron emission tomography (PET) (Fig. 1). Initially the osteomyelitis was treated with a combination of antibiotics and hyperbaric oxygen therapy (HBOT). The ulcer at the pharyngeal resolved, but the submental ulcer sustained. The submental ulcer was excised and the defect was reconstructed successfully with a pendicular pectoralis major muscle flap.

Fig. 1.

Sagittal MRI cervical spine Patient A showing cervical osteomyelitis of C4–7

The following months the patient suffered a progressive neck pain, pain with paraesthesias in the right arm, and swallowing disorders. There was an increased kyphosis of the cervical spine. Although no specimens were cultured, he was treated intensively with antibiotics. A neck brace was adapted. At this time no deficit of the posterior pharyngeal wall was discovered. In the months following his condition deteriorated, his pain and kyphosis increased and he developed bilateral upper extremity paresis [3 according to the Medical Research Council Scale for Muscle Strength (MRC), right arm], (MRC 4, left arm) and paraesthesia’s in both arms. CT scan showed destruction of C3 and C4. The patient was diagnosed with spondylodiscitis C4–C7, due to osteoradionecrosis and a pharyngo-cervical fistula. A posterior fusion of the spine (C2–Th2) was performed, because an anterior approach was not feasible due to severe scarring of the prevertebral region (Fig. 2). Consequently, lifelong antibiotic treatment was indicated. Fortunately the neurologic deficits improved. Six months later, his paresis recovered to a MRC 5 in his arms, and the paraesthesia of his upper extremities remained. The patient suffered a mild spastic walking pattern. A year later an ulcer at the posterior pharyngeal wall was shown, but the clinical situation was stable. Three years after the spinal decompression and stabilization he died of cardiopulmonal disease.

Fig. 2.

Patient A posterior fusion of the spine (C2–Th2)

Patient 2: (Neopharyngeal Ulceration)

A T4N2cM0 hypopharyngeal cancer was diagnosed in this 68-years old female patient 6 years ago. Her medical history showed that she had been successfully treated for breast cancer and a papillary thyroid cancer 16 years ago. For the breast cancer she received surgery, hormonal-, chemo-, and radiation therapy, and the thyroid cancer was treated with surgery and twice with I-131 therapy. The hypopharyngeal cancer, retropharyngeal and level II to V nodes received 70 Gy bilaterally, and two times concomitantly carboplatin and 5-FU. A necrotic ulcer at the posterior pharyngeal wall sustained. Repeated biopsies were negative. After having already neck pain for almost a year, the pain increased and the patient started to have a fever. This was caused by spondylodiscitis of C3-C4. She was treated with antibiotics (for 14 weeks) and HBOT. Subsequently, she suffered a progressive kyphosis. PET/CT scanning showed a cervical osteomyelitis of level C2–C5 with kyphosis and cervical myelum compression. A posterior laminectomy C3 and C4 and a posterior spondylodesis of level C2–C6 were performed. Cultures showed no bacterial growth. The neurologic deficits (neck pain and paraesthesia’s on both hands) sustained, but without any progression. Two years later the patient complained of mandibular pain, resulting from osteoradionecrosis of the left mandibular, for which she successfully received HBOT. Until now, 5 years after surgery, the patient’s neurological condition is stable.

Patient 3: (Oesophageal Dilatation)

The third case describes a 65-year old male, with polyneuropathy due to alcohol abuse in the past. He was diagnosed with a T2N1M0 squamous cell oropharynx carcinoma ten years ago. This was initially treated with primary radiation therapy (with a total dosage of 79 Gy). Because of regional residual tumour, selective neck dissection (SND) region II–IV at the right side was performed. Nine years later a T2NO squamous cell hypopharynx carcinoma was diagnosed. He refused a laryngopharyngectomy, as second best a CO₂-laser excision of the tumour was performed. Due to lympho-angio-tissue invasion and small margins, adjuvant radiation was indicated (66 Gy). The patient developed neck pain and dysphagia. The video-fluoroscopy showed a stenosis at the inlet of the oesophagus. An oesophagus dilatation was performed. The oedema and fibrosis inclined in time. Later, the patient also suffered from a dysfunctional larynx, pharyngeal oedema and a persistent necrotic ulcer in the posterior pharyngeal wall with bone and cartilage exposed. The patient got HBOT. Despite the HBOT, the complaints increased. He had a complete non-functional larynx. A laryngectomy was performed. Histological analysis showed reactive tissue. A few months later the patient developed progressive neck pain and paraesthesias in his arms. MRI showed cervical spondylodiscitis (C3–C4) with epidural extension and compression of the spinal cord at C3, and central canal stenosis C4–C6 with myelopathy and kyphosis. One month later, due to deterioration of the patient’s condition (a distal paresis MCR 4) and bilateral paraesthesia’s on his upper extremities) a decompressing laminectomy C4–C6 with posterior fixation C2–C6 was performed. Postoperatively, the neck pain and paraesthesia’s improved, but patient still suffered a light paresis (MRC 4) of his extremities, and a disturbed gnostic sensibility. The patient was discharged from the hospital. Two years later there were no signs of cervical spondylodiscitis or instability. The patient still had paraesthesia and a light paresis (MCR 4) of his hands and neck pain was treated with morphine. He died 2 years after surgery.

Patient 4: (Voice Button Puncture)

This male patient had a T4N2b hypopharyngeal carcinoma of the post cricoid region for which he received concurrent chemo radiation (carboplatin/5-FU, radiation doses: 35 × 2 Gy). Six months later the patient underwent an oesophagus dilatation because of a dysphagia due to fibrosis of the oesophagus. After 1 year a local recurrence was diagnosed with involvement of the proximal part of the oesophagus. A total pharyngolaryngectomy with gastric pull-up reconstruction was performed. Due to irradical margins, postoperative radiation therapy was indicated, and the patient received local radiotherapy of 30 × 2 Gy.

Eight months later a secondary trachea oesophageal puncture (TEP) was planned. During the procedure no puncture was possible because of the too lateral position of the gastric pull-up. Two weeks later the patient was hospitalized because of a mediastinitis complicated by a bacteraemia and meningitis and systemic antibiotic treatment was started. After recovery, the patient developed progressive motor and sensory function loss of his left arm, and shortly after that the patient complained of neck pain and developed a torticollis to the right side. Additional imaging (MRI) showed a ventral cervical epidural abscess at level C2–Th1, which caused myelum compression. A hemi laminectomy C7–Th1, draining of the epidural abscess and cervical stabilization was performed. Systemic antibiotics were continued over a 6 weeks period. The patient was discharged from the hospital and was referred to a rehabilitation centre. At that time he had a persistent trachea-gastric fistula, paresis of his left arm (MRC 4), and a hypaesthesia of the left arm and hand, neck pain and a poor general condition. The patient died of lung metastases at an age of 53 years one year after the hemi laminectomy.

Discussion

ORN is a condition characterized by devascularized, devitalized or necrotic bone caused by irradiation. Pathogens penetrate easy into the affected tissues and will weaken the bone structures even more, which may lead to instability. Secondary infections occur in approximately 40% [13]. Modern radiation techniques like IMRT (Intensity Modulated Radiotherapy), can reduce the radiation dose in most primary curative settings, so the tolerance dose for bone i.c. the cervical vertebrae, will not be exceeded. In our study the patients were re-irradiated up to a cumulative total dose of more than 100 Gy, which is far above the tolerance dose of bone.

Cervical spondylitis is a rare complication (< 1%) of radiation therapy for head and neck cancer [4, 7, 11, 12, 14, 15]. Involvement of the sub axial cervical spine is even rarer [16]. Spondylitis is difficult to distinguish from acute ORN due to the similar MRI presentation [14]. Spondylodiscitis is an inflammation of two vertebral bodies and one or more intervertebral articular disk [17]. Secondary infections in the cervical vertebrae area have the lowest prevalence of the spine. It can be caused by haematogenous or continuous spread and is described in patients with previous irradiation [17]. Prevertebral abscesses, as in our patients, can result in compression of the myeloma, leading to neurological disability. Abscess formation is present in approximately 50–100% of cases with cervical ORN with secondary bone infections [12].

Just as in our patients, most patients with cervical ORN and with (secondary) cervical infections complain of neck pain, dysphagia, pharyngitis or more unspecific symptoms as fever or weight loss. Which makes it difficult to differentiate symptoms of ORN from non-ORN related complaints in patients treated for head and neck malignancies. When a secondary spondylodiscitis occurs, these symptoms can worsen quickly and cause neurologic symptoms as sensory loss and progressive paresis [2, 5, 6, 11–13, 18, 19].

The infection usually originates in the posterior pharyngeal wall. Pathogens invade through a defect in the mucosa of the (neo) pharynx and spread to the cervical spine, which is more susceptible to infection due to exposure to irradiation [5, 6, 11]. Some authors discuss neck dissection causes impairment of the local lymphoid immune system, resulting in an even greater risk of infection [18]. Also surgical interventions as laryngectomy may result in decrease of anatomical boundaries. Therefore it is reasonable that the combination of previous surgery and irradiation contributes to ORN and infectious cervical diseases like osteomyelitis.

According to the literature, just as in our two first cases, this defect can be caused by a necrotic ulcer at the pharyngeal wall without presence of malignant cells [11]. The necrotic ulcer is caused by tissue damage due to irradiation. Some authors discuss that a necrotic ulcer itself increases the risk at ORN [11, 14].

Cervical infections can also be caused by tissue damage at the posterior pharyngeal wall inflicted by endoscopic procedures or surgery in previously irradiated tissue; for example by TEP [15, 17, 20, 21], CO₂ laser excision of tumour recurrence [22], or dilatation procedures as in 2 of our patients [2].

As described before, due to radiation-induced tissue changes, a disrupted healing process occurs, resulting in increased vulnerability to infection. Therefore, we recommend being cautious with (surgical) interventions in previously re-irradiated fields. In case of persistent neck pain in a previously irradiated patient, especially in cases with recent intervention, ORN and cervical infections should be considered.

A free or pedicled flap is frequently used to restore the posterior pharyngeal wall integrity to avoid contamination of the vertebral column, as well-vascularized tissues create a better healing process in these devitalized areas. Lower trapezius pedicle flap is the most ideal and frequently used in thoracic and cervical spine coverage [17, 23]. In our patients, it was not possible to use a flap. The poor quality of the surrounding mucosa made it hard to believe that the flap covering the defect would get a viable connection with the recipient site.

Antibiotics are the primary treatment of cervical ORN and infections or in combination with surgery [2]. Surgical debridement and/or stabilization are often necessary. Surgery is mandatory when abscesses compress the spinal cord or in case of an unstable cervical vertebral column [2, 5, 7, 12, 13, 15, 23]. If instability occurs, laminectomy with posterior fixation is the most frequently described method [3, 14, 23, 24]. Kouyoumdjian et al. [23] maintain that long isolated posterior or circumferential stabilization are preferred in case of instability or kyphosis. Anterior approaches are usually, and in our patients definitely, not possible due to the poor condition of the tissues covering the anterior part of the vertebral column [23]. Because of radiation-induced tissue changes in our patients, an anterior approach was not possible and the posterior pharyngeal wall could not be restored. Therefore we chose for a posterior stabilization leaving the by ORN and secondary infection affected vertebrae in situ. This intervention was combined with lifelong antibiotic treatment. In our patients, the neurological deficits decreased, and the quality of life improved.

Hyperbaric oxygen therapy (HBOT) increases oxygen tension in hypoxic tissue, thereby stimulating capillary angiogenesis, fibroblast proliferation and collagen synthesis. The value of HBOT in ORN has not been proven but is an option to improve the circumstances for surgery and an enhanced healing process [11].

Conclusion

Cervical osteomyelitis is a rare late complication of treatment for head and neck carcinoma.

Physicians must be aware of cervical osteoradionecrosis or osteomyelitis in patients with prior irradiation (especially in patients who received > 60 Gy), with complaints of neck pain, dysphagia, motoric/sensory changes.

In case of neurological deficits due to cervical ORN, with or without secondary infections, neurosurgical intervention is paramount to relieve spinal cord compression and/or stabilize the cervical spine. Our cases demonstrate that even when an anterior approach is impossible, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. An improvement in quality of life by reducing further neurological deficits can be obtained.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval of the Institutional Review Board at the hospital was obtained for this retrospective study.