|
 
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| SYMPOSIUM - METASTATIC SPINAL TUMORS |
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| Year : 2022 | Volume
: 5
| Issue : 2 | Page : 176-184 |
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Decision making in the management of metastatic spinal tumors
Gautam Zaveri
Jaslok Hospital & Research Centre, Mumbai, Maharashtra, India
| Date of Submission | 07-Oct-2021 |
| Date of Decision | 13-Jan-2022 |
| Date of Acceptance | 08-Feb-2022 |
| Date of Web Publication | 08-Jun-2022 |
Correspondence Address:
Gautam Zaveri
302 Bhaveshwar Kutir, 4th Road Rajawadi, Ghatkopar East, Mumbai 400077, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/isj.isj_101_21
The advent of newer systemic therapies has resulted in improved survival of cancer patients. Increased life expectancy necessitates strategies not only for palliation to improve quality of life but also for lasting local control of the spinal metastasis. In patients with a short life expectancy, palliative surgery involves decompression of neural structures by debulking the tumor and spine stabilization followed by conventional external beam radiotherapy (cEBRT). Ablative surgery involves more aggressive tumor resection followed by cEBRT. The introduction of stereotactic body radiotherapy (SBRT) has challenged traditional paradigms for decision-making further. With SBRT, hitherto radioresistant tumors can also be successfully treated with radiotherapy alone, in selected cases without spinal instability or severe epidural spinal cord compression. Minimally invasive surgical techniques such as percutaneous cement augmentation, percutaneous stabilization, and minimally invasive decompression and tumor resection have further reduced the surgical morbidity, enabling extension of treatment to more sick patients. The eventual decision regarding the treatment strategy is made on a case-by-case basis by a multidisciplinary team along with the patient and his/her family. Keywords: Radiotherapy, SBRT, spinal metastasis, surgery, systemic therapy, treatment strategy
How to cite this article:
Zaveri G. Decision making in the management of metastatic spinal tumors. Indian Spine J 2022;5:176-84 |
| Introduction | |  |
Spinal metastases represent systemic spread of a primary cancer. They represent stage IV or end-stage cancer wherein the expected survival ranges from a few months to a few years. The management of metastatic spinal disease is aimed at palliation, i.e., to improve quality of remaining life at an acceptable risk. Improvement in quality of life is determined by alleviation of pain, preservation or restoration of neurology and function, along with local control of spinal metastasis.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] The benefits of treatment must be weighed against the risks as determined by assessing the morbidity and mortality related to treatment.[12],[13],[14],[15],[16]
Choosing the most appropriate treatment strategy that will enhance quality of life in this group of dying patients, without doing “too much,” is often extremely difficult. The treatment strategy for any individual with spinal metastases must be a shared decision between the patient and a multidisciplinary team involving medical oncologists, radiation specialists, spine surgeons, internists, and pain management specialists. The treatment options for patients with spinal metastases include systemic therapy, radiotherapy (RT), and spinal surgery [Table 1].
| Systemic therapies (chemotherapy) | | |
The extent of systemic spread of a primary cancer determines the overall survival of a patient. The goal of systemic therapies is to contain systemic spread of the primary tumor, thereby prolonging overall survival, progression-free survival, and improving quality of life. The options for systemic therapy include traditional chemotherapy, hormonal therapy, immunotherapy, targeted molecular therapy, and systemic radioisotopes. Newer targeted molecular therapy and immunotherapy regimens have significantly improved the overall survival in select cancers that possess a molecular target.[17]
Systemic therapies have a limited role in obtaining local control of spinal metastasis. Their effect usually takes a longer time to manifest, and the resolution of large symptomatic masses is often incomplete. Hence, systemic therapies are generally reserved for asymptomatic or minimally symptomatic spinal metastases. Lymphoma, myeloma, and Ewing’s sarcoma are exceptions in that they are exceedingly chemosensitive and the tumor response to systemic therapy is rapid, so that surgical decompression may be unnecessary even in patients presenting with major neurologic deficits.[18],[19],[20]
| Radiotherapy | | |
RT has little role to play in controlling the systemic spread of cancer. RT aims to achieve local control of tumor, relieve neural compression, and alleviate bone pain by causing tumor necrosis and shrinkage. RT alone, or as an adjuvant to surgery, is the treatment for metastatic spinal tumors localized to one or two spinal segments. RT is an effective and non-invasive modality for local tumor control.[21]
However, RT is not effective in relieving pain due to significant mechanical instability and in relieving bony compression of the neural elements secondary to pathological fractures.[22] Also, RT has limited potential to affect immediate decompression and maximize neurological recovery. Hence, definitive RT is generally not advised in patients with a longer duration (> 48 h) and greater severity of neurologic deficit (power < grade 3), except for exceedingly radiosensitive tumors such as hematologic malignancies or Ewing’s tumor.[23],[24]
Current techniques of delivering RT include conventional external beam radiotherapy (cEBRT), stereotactic radiotherapy (SBRT), and charged particle therapy. Although SBRT and charged particle therapy are extremely effective for local tumor control, their use in developing nations is limited by lack of widespread availability and high cost.
Based on the response to cEBRT (30 Gy in 10 fractions), spinal metastases have been classified as radiosensitive or radioresistant[25],[26],[27] [Table 2]. Most hematologic malignancies, Ewing’s sarcoma, and metastases from breast, prostate, ovary, small cell lung cancer, neuroendocrine tumors, and seminoma respond well to cEBRT (radiosensitive). On the contrary, metastases from kidney (RCC), colon, lung cancer (NSCLC), thyroid, liver (HCC), melanoma, and sarcoma respond poorly to cEBRT (radioresistant).
Stereotactic body radiotherapy (SBRT) has blurred the distinction between radioresistant and radiosensitive spinal metastases. With SBRT, a larger dose of tightly focussed radiation can be precisely delivered to a small tumor area, resulting in lysis of even tumors that were hitherto considered radioresistant. SBRT has shown excellent results with regard to local tumor control and pain alleviation in both unirradiated and previously irradiated patients.[28],[29] Laufer et al.[30] have reported that local tumor control with intralesional surgery followed by SBRT is comparable to en bloc tumor excision for patients with high grade epidural spinal cord compression (ESCC). Additionally, separation surgery followed by adjuvant SBRT has a significantly lower complication risk compared with en bloc surgery.[31] Hesitation with widespread application of SBRT stems from the lack of randomized controlled trials that confirm superior outcomes and the paucity of data regarding long-term toxicity profile of SBRT [Table 3].
| Surgery | | |
Surgery is another treatment modality that aims to achieve local control of the spinal metastasis by excision of the tumor. Surgery followed by RT has been shown to provide more durable control of the local tumor than either RT alone or RT followed by surgery.[4] Surgery must be considered among the initial modalities for the management of spinal metastases.
Surgery is indicated for spinal metastases with significant spinal instability, significant ESCC, or a major neurologic deficit (power < grade 3). Other indications for surgery include spinal cord compression by retropulsed bone from a pathologic fracture and failure of primary RT [Table 4].
Surgery involves resection of the metastasis and spinal stabilization in order to decompress neural elements, alleviate pain, restore function, and obtain local control of the tumor. The margin for tumor resection could be intralesional, marginal, or wide, and tumor resection could be performed piecemeal or en bloc.
The potential benefits of surgery (76–100% pain relief, 40–75% neurologic improvement, and 30–50% restoration of ambulation) must be weighed against the risks as determined by the morbidity and mortality related to surgery.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] Complications have been reported in 5–65% of patients undergoing surgery.[12],[13],[14],[15],[16] Most frequently reported complications include wound problems, pulmonary complications, and deep vein thrombosis. The 30-day mortality has been reported to be between 0% and 20%. The median survival of patients with spinal metastases ranges from 10 to 15 months. The average 1-year survival ranges from 49% to 61%. The penalty of postoperative complications may be devastating, if it leads to delay in RT or systemic therapy.
Less invasive surgical techniques such as percutaneous cement augmentation, percutaneous pedicle screw insertion, endoscopic decompression, and separation surgery are being developed with the goal of reducing the surgical morbidity and complications.
| Management Strategy | | |
A number of clinicians have proposed classifications, algorithms, and flow charts to integrate the multiple treatment modalities into one decision-making platform. However, the precise treatment strategy to be employed for a particular patient is dictated by individual patient factors, as not all patients will fit neatly within a particular framework. Additionally, decision-making is influenced by the treatment modalities available at a given institution. Currently, the NOMS framework developed by the multidisciplinary spine team at the Memorial Sloan-Kettering Cancer Centre in New York, USA is being widely used by clinicians to aid decision-making.[32] Within this framework, the treatment strategy for individual patients is based on an assessment of the neurologic status, oncologic status, mechanical instability, and systemic disease.
Neurologic assessment
The neurological status of a patient with spinal metastatic disease is an important determinant of functional status, quality of life, post-operative complications, and overall survival.[33],[34],[35] In patients with myelopathic symptoms, life expectancy is a mere 3–7 months. A severe neurologic deficit (power < grade 3 muscle power assessment), bladder dysfunction, and longer duration of ambulatory loss (>48 h) are poor prognostic factors for neurological recovery after treatment.[23],[24],[36],[37]
The assessment of neurological status comprises of clinical evaluation of the patient’s neurologic function and an estimate of the degree of ESCC on magnetic resonance imaging (MRI). The Spine Oncology Study Group has developed a six-point grading system to describe the degree of ESCC on axial T2- and contrast T1-weighted MRI[38] [Figure 1]. | Figure 1: Epidural spinal cord compression (ESCC). Grade 0: Intracompartmental osseous lesion without epidural disease. Grade 1: (A–C): Minimal epidural disease with no spinal cord compression. Grade 2: High-grade ESCC with spinal cord displacement/compression but with visible cerebrospinal fluid (CSF). Grade 3: High-grade ESCC with spinal cord displacement/compression but no visible CSF. In general, low-grade ESCC (grade 0 or 1) can be adequately treated with radiotherapy alone, whereas high-grade ESCC (grade 2 or 3) is best treated with surgery followed by RT, especially when there is a neurologic deficit[38]
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Oncologic assessment
Oncologic assessment involves determining the histology of the primary tumor, assessing the extent of metastatic spread within the body and evaluating the impact of prior treatment.
The histology of the primary tumor is the strongest predictor of survival following surgery for spinal metastases. Slow-growing tumors including breast, prostate, thyroid, and carcinoid tumors generally have the best prognosis for survival. Tumors arising from the kidney and uterus grow at a moderate pace, whereas tumors originating from the lung, liver, stomach, esophagus, pancreas, bladder, and sarcoma grow rapidly and have the worst prognosis. The histology of the primary tumor also provides a clue to the possible responsiveness of the spinal metastases to systemic therapies and RT. Additionally, the histology of the primary tumor provides a clue to the vascularity of the spinal metastases. Metastases from renal cell cancer, thyroid, hepatocellular cancer, melanoma, sarcoma, and giant cell tumor are known to be hypervascular, necessitating pre-operative embolization in order to limit intraoperative blood loss.
Assessment of the systemic spread of the primary tumor is vital for staging the disease. Patients with extensive systemic disease have a poorer survival, so that they are less likely to benefit from major surgical procedures.
Knowledge regarding prior treatment received and response to that treatment is vital in planning further treatment. For example, in a patient who has previously received cEBRT for a solitary thoracic metastasis from lung cancer, and now presents with a grade 1 metastatic epidural spinal cord compression without neurologic deficit, the treatment options may be limited to either SBRT or surgery.
Mechanical instability
Spinal instability refers to loss of integrity of the spinal column that may result in pain, deformity, neurologic deficit, and loss of function. Tumor-related destruction predisposes vertebrae to pathological fractures. Although vertebral fractures result in temporary instability, most fractures heal non-operatively, albeit with varying degrees of collapse. More extensive destruction results in abnormal mobility between adjacent vertebral segments and inability of the vertebral column to bear loads, necessitating surgery for spinal stabilization.
Mechanical pain is severe and movement-related. Pain worsens on turning in bed, when moving from lying down to sitting and from sitting to standing position. Bending forward exacerbates the pain, and the pain also worsens with prolonged sitting or standing. It is relieved in supine position. Mechanical pain must be differentiated from biological pain which is worse in the morning and evening and is relieved with anti-inflammatory medications, steroids, and radiation. Mechanical pain is not relieved by non-steroidal anti-inflammatory drugs, steroids, chemotherapy, or RT.
The Spine Oncology Study Group has developed the Spinal Instability Neoplastic (SIN) score that helps to objectively and reproducibly determine the degree of neoplastic spinal instability[39],[40] [Table 5]. Increasing SIN score correlates with increasing severity of pain and functional disability.[41] Patients with low SIN scores (2–7) typically experience resolution of pain after RT.[42] In contrast, indeterminate (7–12) and high (13–18) SIN scores correlate with higher risk of failure of RT, necessitating surgical stabilization for pain relief and functional improvement.[42],[43]
Systemic assessment
The critical initial step in any patient with spinal metastatic disease is to evaluate his/her ability to withstand the proposed cancer treatment. Assessment of the general condition of the patient, nutritional status, and medical co-morbidities helps to stratify the risks associated with medical or surgical intervention and tailor the treatment strategy.
Another important component of the systemic assessment is to estimate the anticipated survival of the patient. Tokuhashi et al.[44] proposed a scoring system based on six key prognostic factors, namely, general condition, number of extraspinal bony metastases, number of metastases in the spine, presence or absence of metastases to major internal organs, site of the primary lesion, and severity of neurologic deficit. The total score provides a guide to determine the aggressiveness of planned treatment [Table 6]. In patients in whom a short survival is anticipated, major surgical interventions that require long hospital stay and extensive rehabilitation and expose the patient to a higher risk of perioperative complications, should be avoided. However, it must be borne in mind that with the introduction of newer systemic therapies, survival of cancer patients has significantly improved. Hence, discussion with the medical oncologist would aid survival prognostication and help in planning surgical intervention. | Table 6: Modified Tokuhashi scoring system for pre-operative prognostication of survival in spinal metastatic disease[44]
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Based on the aforementioned assessments, the NOMS framework [Table 7] recommends the following decision-making pathway for patients with spinal metastatic disease.[45]
Step 1: The first critical step is the systemic assessment of the patient. Patients who are very frail or lack the will to live are poor candidates for any form of cancer care and may benefit from palliative pain control. Patients with short anticipated survival (< 3 months) may be best treated with non-invasive treatment modalities or minimal access spine surgery.
Step 2: A second critical step is to recognize mechanical instability. Although pathological fractures represent a phase of spinal instability, it is often temporary and the pain settles over time as the vertebra collapses into a stable position. Persistently painful pathological fractures can be treated with percutaneous cement augmentation or minimal access spine stabilization. In contrast, significant spinal instability as determined by a SIN score of >13 can not only result in severe mechanical back pain and loss of function, but also has the potential for causing neurological deficit. It must be treated with surgical stabilization. Neither chemotherapy nor RT is useful in treating significant mechanical instability.
Step 3: Finally, the oncologic status and the neurological status are considered together as follows.
Radiosensitive tumors
cEBRT has been shown to provide durable local tumor control, alleviate pain, and improve neurology in patients with radiosensitive histologies. In patients with exceedingly radiosensitive tumors such as hematologic malignancies, Ewing’s sarcoma, and seminoma, cEBRT can induce rapid cell death within the tumor resulting in neural decompression without damaging the spinal cord, rendering surgical decompression unnecessary even in the presence of high grade ESCC with major neurologic deficits. Metastases from radiosensitive solid organ tumors such as breast, prostate, ovary, and neuroendocrine tumors can be treated with cEBRT alone, provided that the ESCC is grade 0/1a/1b and there is no major neurologic deficit. In patients with a neurologic deficit, there is a narrow window of opportunity (<48 h) wherein emergency surgical decompression may permit superior neurologic recovery than treatment with cEBRT.
Rades et al.[46] reported improved local control of tumor and improved survival among patients with radiosensitive spinal metastases treated with cEBRT, compared with patients with radioresistant tumors. Additionally, these patients had a better chance of being ambulatory post-radiation, and the ambulation was preserved for a longer duration.[21],[47] Maranzano and Latini[26] demonstrated that 67% of breast cancer patients regained ambulation compared with 20% in hepatocellular carcinoma and further showed that myeloma, breast, and prostate had response durations of 16, 12, and 10 months, respectively. Long-course, high-dose RT regimens provide more durable long-term local control than do low-dose regimens.[21],[46]
Radioresistant tumors with low grade ESCC
Tumors labeled as radioresistant require large doses of radiation to induce cell death and tumor necrosis. However, cEBRT is unable to deliver such large tumoricidal doses of radiation to radioresistant tumors without a high risk of radiation-induced toxicity to adjacent organs such as the spinal cord. Compared with cEBRT, a significantly higher dose of radiation is delivered to the tumor tissue with SBRT (> 10 Gy per fraction), resulting in the lysis of even tumors that were hitherto considered radioresistant. The full dose of radiation can be delivered in a single sitting or in 2–3 fractions. SBRT has been shown to provide durable improvement in symptomatology and sustained local tumor control in 88% of the patients, irrespective of tumor histology.[25],[29],[48],[49] Yamada et al.[15],[50] described a series of 811 lesions in 657 patients treated with single fraction SBRT. About 82% of the tumors were traditionally radioresistant and 50% had failed prior to cEBRT. They reported local control rates of up to 98% over 4 years, noting that response rates were irrespective of tumor histology, volume, or prior radiation failure, but rather dose-dependent. Radioresistant tumors with low-grade ESCC (grade 0 or 1) can be treated with SBRT alone for local tumor control. The recurrence rate in patients treated with 24 Gy of SBRT was reported to be 3% at a mean follow-up of 3 years, irrespective of tumor histology.[28],[50] Surgery can be avoided in this group of patients. Where SBRT is unavailable, radioresistant tumors require aggressive surgical resection followed by cEBRT.
Radioresistant tumors with high-grade ESCC
Patients with radioresistant metastasis and high-grade ESCC (grade 2 and 3) are best treated with surgical decompression and stabilization followed by SBRT. In high-grade ESCC, the tumor tissue is closely approximated to the spinal cord. For SBRT to be effective, a radiation dose of 15 Gy must be delivered to the entire tumor volume. However, the assumed maximum safe dose to a single voxel of the spinal cord is 14 Gy.[51] Lovelock et al.[52] have reported failures in local tumor control following high-dose single fraction SBRT in patients in whom some portion of the tumor tissue did not receive the requisite dose of 15 Gy. In contrast, radiation-induced myelopathy has been reported in up to 0.5% of patients treated with SBRT.[51] Hence, SBRT alone is not currently recommended for high-grade ESCC. For a high dose of radiation to be administered in patients with high-grade ESCC, Benzel and Agnelov have proposed that surgery be performed in order to debulk the tumor so as to create a small separation (2–3 mm) between tumor tissue and the spinal cord.[30] This surgery (separation surgery) can be performed using less-invasive techniques, thereby minimizing perioperative morbidity and complications. Percutaneous pedicle screw stabilization can be performed at the same time. Post-operatively, high-dose SBRT can be safely and effectively delivered to the residual tumor tissue. Rock et al.[53] reported a 92% local control rate in patients treated with radiosurgery following open surgical procedures. Moulding et al.[54] reviewed the outcomes in 21 patients with radioresistant metastases causing high grade ESCC who underwent single-fraction SRS after instrumented separation surgery. The 1-year local progression risk after receiving 24 Gy dose was estimated to be 6.3%. In a series of 186 patients with mostly radioresistant histologies who underwent separation surgery followed by high-dose single fraction (24 Gy) or hypofractionated SRS (8–10 Gy), the 1-year local progression rates were 4.1% and 9.0%, respectively.[30] These results were achieved regardless of tumor histology and the degree of pre-operative ESCC.
In centers in which SBRT is unavailable, surgery involves aggressive surgical excision of the spinal metastasis to achieve adequate local tumor control. Total or near total excision of the tumor leaves an anterior column void that requires reconstruction and spinal stabilization. Naturally, such extensive surgeries have higher morbidity and complications. cEBRT is generally administered 3 weeks following such surgery, after adequate wound healing.
| Conclusions | | |
The management of spinal metastases is continually evolving. Current treatment strategies must factor in the improved overall survival of cancer patients. This necessitates long-lasting local control of the spinal metastases, in addition to maintaining pain relief, neurologic function, and ambulation in the long term.
The Neurologic, Oncologic, Mechanical Instability, and Systemic assessments performed as suggested by the NOMS Framework provide the treating team with information for adequate decision-making in patients with spinal metastases. The initial critical step in decision-making is to evaluate the overall health of the patient and prognosticate the survival duration. Patients who are very frail, with multiple comorbidities and whose anticipated survival duration is short (<3 months), are best treated with non-invasive modalities or minimal access spine surgery. The next step is to determine the presence of significant mechanical instability as determined by the SIN score. Significant instability (SIN score >13) necessitates surgical stabilization. Chemotherapy and RT have no role to play in treating significant spinal instability. Persistently painful pathological fractures can be treated with percutaneous cement augmentation. In the last step, the neurologic and oncologic assessments are considered in conjunction. In a stable spine, radiosensitive tumors are best treated with cEBRT, irrespective of the grade of ESCC. However, in patients with a significant neurologic deficit (power < grade 3, loss of ambulation, loss of bladder/bowel function), there is a narrow window of opportunity during which surgical decompression may allow neurologic recovery. Hence, except for exceedingly radiosensitive tumors such as hematologic malignancies or Ewing’s sarcoma in which tumor response to cEBRT is rapid, it is probably safer to offer surgery in patients with significant neurologic deficit. For radioresistant tumors with low-grade ESCC, SBRT is the treatment of choice. Finally, for radioresistant tumors with high-grade ESCC, the current treatment recommendation is separation surgery followed by SBRT. In centers in which SBRT is not available, radioresistant tumors are treated with aggressive surgical tumor excision and spinal reconstruction followed by cEBRT.
Ethical policy and institutional review board statement
Not applicable.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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