Complications of Surgery and Radiosurgery in Spinal Metastasis




Abstract


The overall oncologic management of patients with metastatic disease is fraught with many challenges. With patients living longer due to advances in care, optimal surgical and radiation options for treating spinal metastases are paramount to preserving quality of life in these individuals. A multidisciplinary approach to managing these patients involving interventional radiologists, radiation oncologists, and plastic surgeons, among others, has demonstrated enormous benefits in preventing and managing complications. Preoperative attention to vascular blood supply, dosing constraints, and systemic risk factors for hemorrhage and infection can help reduce the occurrence of complications. Similarly, intraoperative adjuncts such as cement augmentation, body warmers, radiofrequency cauterization devices, and intraoperative neurophysiologic monitoring can also mitigate surgical and hardware-related complications. Each patient should ultimately be evaluated on a case-by-case basis for the ideal treatment strategy.




Keywords

spine, spine tumor, metastasis, radiosurgery, surgery, stabilization

 




Highlights





  • Hemorrhage, wound dehiscence/infection, and hardware failure are the most common complications during and after spinal tumor surgery.



  • Esophagitis, myelopathy, and development of vertebral body compression fractures are the most common significant complications after spinal tumor radiosurgery.



  • Many of these complications can be mitigated by appropriate preoperative management; however, subsequent interventions still may be required with the goal of preventing systemic deterioration and preserving quality of life.





Background


Technologic and medical breakthroughs in the diagnosis and treatment of metastatic disease have markedly increased life expectancy in patients with cancer. While effective chemotherapy, biologics, and immunotherapy have had profound impact with specific tumors, advances in radiation therapy and a better understanding of optimal surgical strategies have concordantly played a vital role in the multidisciplinary management of these patients. The spine represents the most common skeletal site for metastatic disease, affecting up to 30% of patients with solid organ malignancies. Radiation and surgery are the principal modalities used to achieve local tumor control in the setting of spine metastases. The NOMS decision framework takes into account four sentinel decision points: Neurologic, Oncologic, Mechanical Stability, and Systemic Disease. This framework can integrate evidence-based guidelines to determine the optimal treatment strategy. Stereotactic radiosurgery (SRS) represents a significant advance over conventional external beam radiation (cEBRT) because responses to SRS are both histology- and volume-independent when used in the upfront setting or as a postoperative adjuvant treatment. From an oncologic perspective, tumoral responses are no longer dictated by the radioresistance seen with cEBRT for most solid tumor malignancies. Despite exponentially better tumor control achieved with SRS, surgery continues to play a critical role in the treatment of patients with neurologic indications, including high-grade epidural spinal cord compression (ESCC) with or without myelopathy, and the treatment of radioresistant tumors and mechanical instability. Superior outcomes have been demonstrated in patients with symptomatic solid tumor ESCC treated with surgical decompression and stabilization compared with radiotherapy alone.


Despite significant advances in surgery and radiation, treatment-related complications need to be weighed carefully in decision-making. Operative techniques and instrumentation have improved, but oncologic and medical comorbidities can significantly impact surgical outcomes. Additionally, the last decade has witnessed tremendous advances in the technology used to deliver SRS, and significant effort from multiple institutions has centered on defining optimal tumoricidal doses while minimizing toxicity to organs at risk. Tight dose constraints have been established to prevent injuries to structures such as the spinal cord, esophagus, and vertebral body. These complications can significantly diminish quality of life, but improved outcomes can be achieved by identifying and treating risk factors and aggressively managing complications.



Red Flags





  • Thrombocytopenia that does not respond to transfusion is an absolute contraindication to proceeding with surgery.



  • Reoperations, previously irradiated tissue, neutropenia, and vascular endothelial growth factor (VEGF) inhibitor therapy (e.g., bevacizumab) represent risk factors for wound complications.



  • Known risk factors for hardware failure requiring possible revision surgery include the following: extensive tumor involvement of the pedicle and vertebral body, previously irradiated bone, osteoporosis, extensive chest wall resection, and constructs greater than six contiguous spinal levels.



  • Radiosurgery of spinal metastases can cause radiation-induced complications of the esophagus, brachial plexus, and spinal cord and can predispose treated vertebrae to compression fractures.






Prevention


Tumor Hemorrhage


Hypervascular tumors should be considered for preoperative digital subtraction angiography (DSA) to identify the vascular anatomy supplying spinal metastases and to assess the potential to embolize large arterial feeders to the tumor. A laundry list of tumors that often benefit from preoperative embolization is provided in Table 60.1 . In general, tumors originating from vascular organs, such as the kidney and thyroid gland, frequently exhibit hypervascularity, as do tumors with “angio” or “hemangio” in their name. The most significant misnomer is solitary fibrous tumor, which was previously called hemangiopericytoma and was found consistently to be the most hypervascular tumor on the list. A tumor blush is often visible on angiographic injection of the segmental arteries feeding the tumor, with the intensity of the blush indicative of the vascularity of the tumor. Infusion of polyvinyl alcohol particles and liquid embolics (e.g., N -butyl cyanoacrylate [NBCA]) and deployment of detachable platinum coils have been described as effective embolization methods. When tumors are not supplied by a radiculomedullary artery, such as the artery of Adamkiewicz, selective embolization can be performed with extremely low complication rates or significant long-term morbidity. Reduction in intraoperative blood loss by up to 50% can be seen, ultimately resulting in fewer blood transfusions and hypotensive episodes. The timing between embolization and surgery remains unclear, although most centers will operate within 72 hours of embolization to obviate revascularization of the tumor.



TABLE 60.1

Hypervascular Solid Organ Spinal Metastases








  • Renal cell carcinoma



  • Hemangiopericytoma (solitary fibrous tumor)



  • Follicular/papillary thyroid carcinoma



  • Neuroendocrine tumors



  • Paraganglioma



  • Hepatocellular carcinoma



  • Cholangiocarcinoma



  • Angiosarcoma



Other significant considerations for tumor hemorrhage are related to systemic issues preventing normal clotting. Coagulopathy and thrombocytopenia including those related to liver dysfunction (especially in the setting of hepatocellular carcinoma), factor deficiencies, or marrow suppression related to chemotherapy or wide-field radiation are primary factors. Appropriate transfusion of fresh frozen plasma (FFP) and/or platelets as well as vitamin K replacement are critical to reducing blood loss. Understanding of the timing of nadir counts related to chemotherapy can often be used to anticipate recovery. Discontinuing medications that impact platelet function (e.g., nonsteroidal antiinflammatories) or cause low platelets (e.g., heparin-induced thrombocytopenia) may often allow clotting abnormalities to correct. One contraindication to surgery is thrombocytopenia secondary to marrow suppression from wide-field irradiation or advanced disease. Chronic thrombocytopenia cannot be managed effectively because these patients often sustain uncontrolled intraoperative or postoperative hemorrhage with the need for massive platelet transfusions, often resulting in compressive clot at the laminectomy site. Early hematology consultation and bone marrow biopsy are often helpful in establishing the etiology and expected time to recovery of clotting disorders.


Wound Complications


Wound breakdown, dehiscence, and infection are the most common complications after instrumented spine procedures for metastatic disease. Major factors impacting wound healing include systemic therapy (e.g., glucocorticoids, biologics, or chemotherapy), poorly controlled diabetes mellitus, and hypoalbunemia from poor nutrition. Surgical risk factors include significant blood loss and increased length of surgery. Neutropenia with an absolute neutrophil count (ANC) less than 1000 cells per microliter also signifies poor immunologic function and conveys a higher chance of infection. Treatment with granulocyte colony- stimulating factor (G-CSF), such as Neupogen (Amgen, Thousand Oaks, CA), will often correct the neutropenia within 24 hours of infusion, reducing operative risks. Previously irradiated tissue, particularly preoperative cEBRT within 6 weeks of surgery, results in a very high risk of infection. With the integration of neoadjuvant radiation into spine treatment paradigms, it is important to note that SRS reduces the rate of wound problems compared with cEBRT.




Management


Tumor Hemorrhage


Intraoperative control of tumor hemorrhage can be addressed by a number of strategies. Direct cauterization with monopolar and bipolar cautery can be used; however, monopolar cautery should be avoided when near the thecal sac, spinal cord, or nerve roots to prevent thermal injury. Radiofrequency energy bipolar sealers with built-in saline irrigation, such as the Aquamantys (Medtronic, Fridley, MN), are also excellent tools for controlling bleeding without char or smoke. Hemostatic matrix agents, thrombin, and direct pressure with cottonoids can also be used as needed. Compression with rolled strips of thrombin-soaked Avitene (Bard, New Providence, NJ) balls packed into the vertebrectomy defect is superb for controlling bleeding. Intermittent irrigation with 3% hydrogen peroxide can serve as both hemostatic control agent and bactericide. Even in cases where intraoperative hemostasis is adequately achieved, postoperative hemorrhage can result in rapid neurologic deterioration. Early identification and correction of coagulopathy should be addressed, especially in high-risk patients with hepatocellular carcinoma, multiple myeloma, and lymphoma. Hypothermia can induce coagulopathy that can contribute to intraoperative tumoral hemorrhage. In vitro, animal, and clinical studies have demonstrated that temperatures below 35°C can induce platelet dysfunction, decreased platelet count, and diminished synthesis of clotting enzymes and plasminogen activator inhibitors. Furthermore, a progressive decrease in body temperature correlates with delays in the initiation of thrombus formation. Appropriate intraoperative management can help reduce the occurrence of these phenomena with the use of body warmers and infusion of warmed intravenous fluids.


Coagulopathy can often be recognized intraoperatively as previously clotted blood begins to lyse or be predicted based on excessive blood loss of greater than 2 liters or transfusion of greater than 5 units of packed red blood cells (pRBCs). If possible, FFP and platelets should be given intraoperatively rather than in the postoperative period. Postoperative transfusion may result in tenacious local clot that cannot be evacuated even with epidural drains. Should evidence of an epidural hematoma develop with an acutely worsening neurologic examination or spinal cord compression as determined by imaging, expeditious return to the operating room for exploration and hematoma evacuation can salvage a good neurologic outcome. Subfascial/epidural drains are often used postoperatively to prevent subacute hematoma complications; however, their utility in mitigating emergent epidural hematomas is less clear.


Wound Infection and Dehiscence


Surgical site infections, osteomyelitis, and paraspinal abscesses after spine tumor surgeries range from 9% to 14%, with Staphylococcus aureus being the most common organism. Perioperative antibiotics should be given within one hour of skin incision and continued for 24 hours postoperatively in all cases. Vancomycin powder placed in the wound before wound closure is associated with a lower rate of deep spinal wound infection with minimal side effects. In nonseptic patients who develop small postoperative collections concerning for infection, image-guided biopsy of the lesion should be attempted to isolate an organism. Systemic antibiotic treatment should then be tailored for the organism and its sensitivities. For large abscesses with thick capsules that are unlikely to be resolved by systemic treatment alone, wound exploration, washout, and debridement may be required. Assistance from infectious disease specialists in most cases is advised.


For patients requiring wound revision surgeries due to wound infection, dehiscence, or symptomatic pseudomeningocele, complex closures performed with the assistance of plastic surgeons have resulted in better outcomes and decreased occurrence of developing further complications. The use of local rotational or transpositional flaps (e.g., trapezius or latissimus turnover flaps) provides vascularized tissue to the defective area that accelerates healing and can aid in bacterial clearance. These flaps are critically important in the setting of previously irradiated tissue.


Another major consideration for preventing wound infections and dehiscence is the timing and order of radiotherapy and surgery. Complications are significantly reduced when surgery is followed by radiotherapy as opposed to radiotherapy followed by surgery. Advances in intensity modulated image-guided radiotherapy (IMRT) allow radiation oncologists to target spinal tumors using multiple beam trajectories and in the postoperative setting; generally results in a significantly lower dose to the region of the healing skin incision compared with cEBRT, which delivers a significant dose to the operative corridor.


Cerebrospinal Fluid (CSF) Leak


The majority of spine tumor surgeries are for epidural lesions; therefore incidental durotomies can become a major source of morbidity. Durotomies are typically managed based on the size of the defect. A primary closure should always be attempted. Muscle patches and dural/fibrin sealants are commonly used. For large defects, dural patch grafts such as Dura-Guard (Baxter, Deerfield, IL) can effectively create a watertight repair. A Valsalva maneuver intraoperatively should confirm a watertight closure. In cases where this cannot be achieved or patients are otherwise at high risk for pseudomeningocele formation, a lumbar drain can be placed. Drainage of 10 mL per hour is often used with the goal to taper down drainage until the leak is confirmed as sealed; however, the hourly drainage volume can be increased, if needed, as long as the patient does not develop a low-pressure headache or subdural collections on imaging. Patient positioning is also important because lower thoracic and lumbar CSF leaks are best managed by keeping patients flat for at least 24 hours postoperatively; in comparison, the head of the bed is kept up for patients with cervical and upper thoracic leaks. Postoperative signs and symptoms of intracranial hypotension should be assessed, including positional headaches improved with recumbency, altered mental status, and fluid drainage directly from the wound. Vacuum-assisted subfascial drains should be used with extreme caution because the negative pressure generated can exacerbate small dural defects and prevent proper healing. Likewise, lateral and anterior approach surgeries requiring chest tube insertion are at high risk for the same issue if kept on suction. High-volume thin output from subfascial drains or chest tubes should raise concern that a CSF leak persists. In cases refractory to conservative management, re-exploration to identify and primarily repair the defect may be required. For many of these situations, plastic surgery assistance is recommended with complex closures utilizing local rotational flaps; in severe cases, omental rotational or free flaps may be required.


Hardware Failure


Hardware failure is characterized by screw pullout, rod fracture, or interbody device migration. Risk factors include previous irradiation, extensive pedicle/vertebral body tumor involvement, postmenopausal or androgen blockade–induced osteoporosis, junctional spine instrumentation (cervicothoracic or thoracolumbar), and chest wall resection. Strategies to prevent screw pullout include cement augmentation of pedicle screws with polymethyl methacrylate (PMMA) in the thoracic and lumbar spine, which improves pullout strength and biomechanical stability of implanted instrumentation. The recent US Food and Drug Administration approval of fenestrated screws allows the injection of cement material directly into the screw to support fixation. Construct length is also an important factor for hardware failure. Extending constructs one to two levels when there is extensive multilevel tumor involvement can decrease stress on the entire construct by distributing shearing forces.


Radiation Toxicity


Understanding radiation dose and fractionation when treating spinal metastases can help reduce the incidence of radiation toxicity. Collateral effects to the skin, esophagus, peripheral nerves, and spinal cord have been reported, manifested as symptoms such as dysphagia, odynophagia, radiculopathy, myelopathy, or other focal sensorimotor deficit. Strict dose constraints for all organs at risk have been established to minimize toxicity. In certain cases, organ displacement via saline infusion into the retroperitoneum can be used to displace also the kidney or bowel several centimeters, creating a more favorable target for SRS of thoracolumbar spine metastases.


Radiation-induced myelopathy is a rare complication but can also cause neurologic deficits based on the dose received by the spinal cord. Occurring infrequently in about 0.4% of treated patients, it has a typical time frame of 6 months for development of symptoms. A maximal spinal cord dose constraint of 14 or 10 Gy to 10% of the spinal cord minimizes the occurrence of myelopathy. Although studies have failed to show reliable treatment strategies for this complication, steroid administration has been reported with varying degrees of success.


Non-neurologic Injury


Radiation-induced esophagitis is the most common side effect of radiosurgery to the cervical and thoracic spine. Patients typically present with dysphagia and odynophagia, and although most cases are self-limited, more serious complications can occur. Mild cases can be treated by slow transition to a mechanical soft diet and application of topical anesthetics (e.g., 2% viscous xylocaine) to help reduce symptoms until inflammation subsides. Radiation-induced strictures can develop, but multiple repeat dilations place patients at risk of esophageal perforation. High dose, single-fraction paraspinal SRS has demonstrated a low rate (~7%) of grade 3 or higher acute or late esophageal toxicity, and more recent dose constraints have decreased this risk further.


Radiation recall is the phenomenon of local inflammatory reaction that occurs in an area of irradiation after the administration of certain chemotherapeutic agents. This is a poorly understood complication of cancer treatment; however, it can result in profound complications, especially to tissues in the vicinity of previous surgery. The most common agents that have been shown to induce radiation recall include the anthracyclines, taxanes, antimetabolites, and epidermal growth factor receptor (EGFR) inhibitors. The severity of radiation recall varies widely; however, severe cases can result in esophageal perforation and skin necrosis and ulceration. When it occurs in the paraspinal region after surgical intervention, the risk of wound dehiscence significantly increases. Although the prediction is unclear as to which patients will be affected and in what time frame, appropriate management, including immediate cessation of the offending agent, should be underscored.


De novo and progressive vertebral compression fractures (VCFs) after spinal radiosurgery range from 3% to 40%, with a median time to fracture of 3 to 11 months. However, the SRS-associated symptomatic fracture risk requiring surgical intervention is quite low at approximately 7%, and independent of administered dose. For patients with pain refractory to conservative measures, percutaneous cement augmentation, pedicle screws, or open surgery should be considered. Excellent pain outcomes after these interventions are reported in the 80% to 90% range.


Jun 29, 2019 | Posted by in NEUROSURGERY | Comments Off on Complications of Surgery and Radiosurgery in Spinal Metastasis
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