Resumo

Nesta secção o especialista Jeffrey D. Bradley, MD (Washington University in St. Louis St. Louis, MO) confronta seu ponto de vista com as opiniões dos especialistas Jacob M. Buchowski, MD, MS (Washington University Orthopedics St. Louis, MO) e Peter S. Rose, MD (Mayo Clinic Rochester, MN) sobre qual melhor tratamento para um determinado paciente com câncer metastático da coluna torácica com origem primária no pulmão. Os especialistas enumeram as principais indicações da cirurgia e da radiocirurgia e suas  vantagens e desvantagens comparativas. O Dr. Jeffrey D. Bradley tende a indicar a radiocirurgia, enquanto os Drs. Jacob M. Buchowski,) e Peter S. Rose enfantizam sobre as possibilidades cirúrgicas para o caso. Veja a seguir as opiniões referentes a um caso de um paciente do sexo masculino de 47 anos com metástase em coluna torácica por câncer do pulmão.
FONTE: SPINELINE: volume IX · issue 5 september · october 2008

CURVE/COUNTERCURVE
Jeffrey D. Bradley, MD
Washington University in St. Louis
St. Louis, MO
Jacob M. Buchowski, MD, MS
Washington University Orthopedics
St. Louis, MO
Peter S. Rose, MD
Mayo Clinic
Rochester, MN
SpineLine Section Editor:
Heidi Prather, DO
Washington University
St. Louis, MO

Case Presentation History: A 47-year-old white man with a history of limited-stage small cell right lung cancer presents with worsening right chest wall pain and acute-on-chronic upper thoracic back pain. MRI of the thoracic spine (below) shows a soft tissue mass in the right paraspinal region, with extension into the T3 vertebral body associated with mild canal stenosis but no cord compression. One year prior to this presentation, he was treated with chemoradiation therapy to 4500 cGy with 150 cGy twice-daily (BID) fractions followed by prophylactic cranial irradiation to 2500 cGy.

Physical Examination: The patient is an alert, oriented, well-appearing gentleman with thoracic kyphosis. Examination of the head and neck, cardiovascular system and abdomen was benign. The lungs were clear to auscultation, bilaterally. Point tenderness was elicited in the mid upper back. Manual muscle testing revealed normal motor strength in bilateral upper and lower extremities. Sensory exam and muscle stretch reflexes were normal in all extremities. What are your treatment recommendations?

Jeffrey D. Bradley, MD, Responds
Background. Spine metastases are a common problem for patients with cancer. Presenting symptoms may include pain, parasthesias, sensory and motor deficits, loss of bowel or bladder control or paralysis. Appropriate management of spinal patients with spine metastasis is extremely important in order to maintain or improve the patient’s quality of life. Treatment options include surgery and radiation therapy. Obtain a surgical consult when the offending lesion risks spinal structural integrity or causes motor or sensory deficits. Conventional radiation therapy is offered postoperatively or for palliation when surgery is not an option. Stereotactic radiosurgery (SRS) is now available for patients with spine metastases. It offers excellent pain control resulting from a single session of high-dose radiation therapy.
As spine SRS has only been available for the past few years, its role with respect to spine care continues to evolve. 

Presentation. Small cell lung cancer continues to have a relatively poor prognosis. The Surveillance Epidemiology and End Results registry suggests that small cell lung cancer comprises 13% of all lung tumors.1 Approximately two thirds of patient have metastases at initial presentation. The other third has limited-stage disease confined to the thorax. Patients with metastatic disease are treated primarily with chemotherapy. Patients with limited-stage disease are treated with a combination of chemotherapy and radiation therapy. Despite aggressive treatment, about 75% of limited-stage patients eventually develop metastases and succumb to their disease. Common sites of distant metastases in small cell lung cancer include the brain, bone, liver and adrenal glands. Bone metastases occur in approximately 30- 40% of patients with lung cancer.2 The median survival of this group is < 6 months and the five-year survival < 5%.2 Small cell lung cancer responds very well to both chemotherapy and radiation therapy. When radiation therapy is given in conventional doses, these cancers are locally controlled the majority of the time. However, surviving cancer cells of this type tend to repopulate and metastasize quickly, frustrating the patient and those caring for them.

Our patient’s presentation is not uncommon. Only one year after chemotherapy and radiation therapy was given to attempt cure, he developed a solitary metastasis in the T3 vertebral body.
This vertebral body had received prior radiation therapy. The spinal cord in the T3 region was treated to tolerance, receiving 36 Gy in 1.5 Gy fractions delivered twice daily. The patient presented with back pain at the level of the metastasis. On physical exam, he had no motor or sensory deficits. The MRI revealed a metastasis within the T3 vertebral body. There was no tumor involvement of the spinal canal. Importantly, this patient’s metastatic workup included chest, abdomen and pelvis CT, and a brain MRI which showed no evidence of distant metastasis.

Treatment Considerations. Initially, it is important to clarify the structural cause of the patient’s symptoms. If the MRI shows spinal instability or cord compression, surgery must be
strongly considered. In 10% of cancer patients, back pain arises from spinal instability. 3 The mechanical pain of instability doesnot respond well to radiation therapy, systemic treatment with chemotherapy or bisphosphonates. For patients with spinal cord compression, a randomized trial comparing surgery to immediate radiation therapy demonstrated a clear advantage to early surgical intervention.4 Significantly more patients in the surgery group (42/50, 84%) than in the radiation alone group (29/51, 51%) were able to walk after treatment (p=0.001). Likewise, surgery reduced the need for corticosteroids (p=0.009) and opioid analgesics (p=0.002).

Other factors considered when planning surgery include tumor type, distant metastasis, and the extent of spinal disease.
Carefully contrast anticipated surgical morbidity with the patient’s expected survival and performance status Tumor specific factors such as radiosensitivity affect the likelihood of palliation with radiotherapy. While renal cell carcinoma and melanoma are less responsive to radiation therapy, small cell lung cancer and lymphoma tend to respond well.

Conventional radiation therapy consists of a series of daily radiation therapy treatments. In the United States, a typical dosing scheme employs 30 Gy over 10 daily fractions. Most patients with spine lesions and other distant metastases or those considered poor surgical candidates are offered conventional radiation therapy. In-field recurrence rates across multiple cancer types range from 20% to 50%.5 About 65% of patients report an improvement in pain control following conventional external beam radiation therapy.6

Stereotactic radiosurgery remains relatively new. Spinal radiosurgery developed from brain radiosurgery, which achieves approximately 90% local control of metastatic brain lesions.
This technique, delivered in one to five fractions, provides both excellent pain relief and local control of spinal metastases. Adequate pain control has been reported between 85% and 96%, compared with 56% to 66% with conventional external beam radiotherapy with or without surgery. Local tumor control has also been excellent, with reported rates between 96% and 100%.

Gerszten et al7 published the prospective outcomes of radiosurgery for 500 cancerous spine lesions in 393 patients. With a mean 21-month follow-up interval, pain and local control were 86% and 90% respectively. Additionally, no cases of radiationinduced spinal cord injury was reported, despite a history of prior radiation therapy in most patients.7 A review of 49 patients with 61 lesions treated with SRS between May of 2001 and May of 2003 was performed by Ryu et al.8 Single fraction doses of 12 to 16 Gy were used. Complete or partial pain relief was achieved in 85% of the treated lesions.

Spinal radiosurgery candidates include patients without
epidural compression from tumor, less than two or three spine
lesions, and those able to lie still for treatments lasting a minimum
of one hour (depending on the technology).

Figure 2. Spine radiosurgery planning target volume (PTV) shown in blue on the right of the image. The radiation dose prescription
in this case was 2400 cGy to the PTV (yellow line on the isodose curve image).

I would recommend palliative spine radiosurgery for thi patient. The reasoning for this recommendation has to do with the limited life expectancy of patients with metastatic small cell lung cancer, the inability to deliver additional radiation to the spinal cord, and the encouraging results from spine radiosurgery with respect to relief from pain and local control. Figure

2 shows the planning target volume (PTV) in blue color on the right of the image. The radiation dose prescription in this case was 2400 cGy to the PTV (yellow line on the isodose curve image). We planned this patient’s treatment with both MRI and CT, contouring the target on the MRI and calculating the radiation dose on the CT images. The treatment was delivered using intensity modulated radiation therapy (IMRT) on the Varian Trilogy unit using cone-beam CT for daily set up and delivery. The spinal cord was limited to 1000 cGy maximum dose using guidelines defined by Gerszten at al.7

In general, surgery would be recommended for a patient with a limited number (< 3 sites) of distant metastases and a relatively favorable prognosis. Small cell lung cancer responds very well to radiation therapy and is one of the histologies that is expected to be locally-controlled with radiotherapy. By analogy, even patients with early-stage small cell lung cancer do not generally undergo surgery, but are treated instead with chemoradiation because the local control rates are similar between the two and the most frequent mode of failure is distant metastasis.

Patients with spinal cord compression have been excluded from the spine radiosurgery reports thus far. This is because the radiation dose fall-off between the tumor and the adjacent spinal cord needs approximately 3 mm to achieve a tumoricidal dose of 14-16 Gy to and < 10 Gy to the spinal cord. Therefore, surgical resection and stabilization is recommended for patients with cord compression or neurological decline.

References
1. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539-4544.

2. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588-1594.

3. DeWald RL, Bridwell KH, Prodromas C, et al. Reconstructive spinal surgery as palliation for metastatic malignancies of the spine. Spine. 1985;10:21-26.

4. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366:643-648.

5. Rades D, Stalpers LJ, Veninga T, et al. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005;23:3366-3375.

6. Hartsell WF, Scott CB, Bruner DW, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97:798-804.

7. Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007;32:193-199.

8. Ryu S, Rock J, Rosenblum M, et al. Patterns of failure after singledose radiosurgery for spinal metastasis. J Neurosurg. 2004;101 Suppl 3:402-405.

Jacob M. Buchowski, MD, MS and Peter S. Rose,
MD, Respond

After the lung and liver, the skeletal system is the third most common site for metastases. The most common skeletal metastases occur in the spine. Of the 1.2 million patients diagnosed with cancer in the United States each year, 10% to 30% have symptomatic spinal metastases at presentation. On autopsy, up to 70% of cancer patients have vertebral deposits.1-5 Involved in 70% of spinal metastatic disease, the thoracic spine is affected most frequently. The lumbosacral spine is affected 16% to 22% of the time. The cervical spine is affected in 8% to 15%.6 Malignancies most likely to metastasize to the spine include breast cancer, prostate, renal cell, hematopoietic, and thyroid cancer.7

Spinal metastases may involve the bone, epidural space or the paravertebral soft tissues. Patients may be completely asymptomatic or present with a mass, pain, sensory disturbance, motor deficits, loss of bowel or bladder control. Without intervention, the natural history of metastatic spine disease is one of symptomatic progression and, potentially, complete paralysis.

Consequently, careful evaluation and appropriate management is extremely important and greatly affects the patient’s quality of life. Options include surgery, radiation therapy, and chemotherapy.

Surgical indications include progressive neurologic deficit, spinal instability, intractable pain, tumor not responsive to radiation or chemotherapy. Occasionally, tissue diagnosis is not obtainable through needle biopsy and open sampling is required. Radiation therapy is used for palliation when surgery is not an option or necessary. In addition, postoperative radiation may reduce the likelihood of local recurrence.

This 47-year-old man who, approximately one year prior to this presentation, was diagnosed with limited stage small cell lung cancer of the right lung and was treated with chemotherapy and radiation. He subsequently presented with increasing right chest wall pain and acute-on-chronic upper back pain. Work-up demonstrated a right paraspinal mass anterior to T3, T4 and T5 extending to and invading the T3 vertebral body and its posterior elements. Tumor invasion has resulted in a pathologic compression fracture of T3 and bowing of the posterior vertebral body into the spinal canal. Together, these changes result in mild to moderate central canal stenosis, but significant cord compression or cord signal change.

Fortunately, the patient demonstrated normal motor strength in both the upper and lower extremities with no evidence of sensory loss. Hyperreflexia or other upper motor neuron signs were not reported, but the patient denied ambulation or balance difficulties. Even though he had no evidence of distant metastases based on a CT scan of the chest, abdomen and pelvis and MRI of the brain, his overall prognosis is not favorable, as patients with bony metastases due to small cell lung cancer have a median survival of six months or less and a five-year survival of less than 5%.8 Surgical intervention could be considered despite this patient’s relatively poor prognosis for several reasons. First, this patient’s pathologic vertebral body fracture involves the entire vertebral body and its posterior elements on the right side. This degree of involvement implies some degree of potential spinal instability.

In addition, it is certainly possible, if not likely, that the patient’s increasing upper thoracic back pain is due to large extent to the pathologic fracture. As this kind of pain is mechanical in origin, it is less likely to respond to additional radiation therapy, chemotherapy or treatment with bisphosphonates. Thus if the patient continues to have significant symptoms, surgical intervention (whether consisting of stabilization with or without tumor resection and reconstruction or vertebroplasty/kyphoplasty with or without tumor ablation) could be considered.

Surgical treatment also has to be considered as the patient has already received conventional radiation therapy to the T3 region with the spinal cord having been treated to tolerance and, thus, he is unlikely to be a candidate for additional conventional radiation therapy. Although he may be a candidate for stereotactic radiosurgery, this modality has limited availability and fairly limited clinical experience.9,10 Furthermore, the use of stereotactic radiosurgery for re-irradiation of paraspinal tumors is even less common, although, as a salvage therapy, good results have been reported. For example, Wright and colleagues reported results of stereotactic reirradiation of 37 patients with mean time to second failure of 13 months.11 To complicate matters further, stereotactic radiosurgery remains precise only to 1-2 mm. Thus patients with significant epidural disease may not have enough clearance between their spinal cord and the tumor margin to allow safe application.12 If epidural involvement increases, this modality becomes less rational. In essence, surgical intervention may become necessary to prevent further tumor progression and paraplegia.

Patchell and colleagues performed a prospective randomized trial comparing surgical decompression and stabilization to radiation therapy and demonstrated significant advantages of direct surgical decompression and radiation treatment compared to radiation alone.13 Similarly, a recent meta-analysis demonstrated that surgical patients were more likely to be ambulatory after treatment than patients treated with radiation alone.14 Thus, one should consider surgery if the MRI scan were to demonstrate cord displacement from its normal position in the spinal canal from either an epidural mass or fracture.

Given the patient’s current neurological status, anticipated survival of six months or less, and an expected five-year survival of less than 5%, a radiation oncologist evaluation for possible stereotactic radiosurgery is recommended. If, after stereotactic radiosurgery, the patient had continued unrelenting and unremitting pain, we would consider surgical stabilization. Surgical options would include open tumor resection and reconstruction or vertebroplasty/kyphoplasty. Although cement augmentation would be less invasive, the destruction of the posterior vertebral wall, significantly increases the chance of cement extravasation.

If the patient was not a candidate for stereotactic radiotherapy, we would very cautiously recommend surgical stabilization with combined tumor resection and reconstruction given the presence of mild to moderate spinal canal stenosis and anticipated continued tumor progression, but with the realization that even with surgery there would be a high chance of local recurrence since no further radiation could be delivered to the surgical field.

To complicate matters further, if surgical intervention was elected, the decision would have to be made whether an intralesional resection of the T3 metastasis was adequate or whether an en-bloc spondylectomy should be performed. By description, this patient appears to have a solitary focus of metastasis. In these patients, consideration can be given to en-bloc surgical excision of the lesion.15 Whether patient survival is improved by aggressive, en-bloc spondylectomy surgery remains unknown.

En-bloc resection decreases the risk of local recurrence and is especially valuable in patients for whom limited adjuvant therapies exist and in solitary lesions after a long disease-free survival.
Finally, the surgical approach must be individualized for patients. The vast majority of metastatic lesions are located in the vertebral body, as in this patient who also has a large soft tissue mass. Often an anterior approach would seem to be the most direct access for surgical treatment. However, in patients with diminished pulmonary function from local or metastatic disease (as in this patient’s chemoradiation treatment for lung cancer), thoracotomy confers significant morbidity. A posterior transpedicular or extracavitary approach can be very successfully employed in the treatment of these patients and avoids the morbidity of violating the chest wall.16

The ultimate treatment would obviously have to be tailored to the patient; clear discussions with the patient, family and medical team about treatment benefits and morbidities are necessary to form an appropriate plan. Although this patient’s ultimate prognosis is poor, aggressive treatment in the form of surgery, radiation therapy or chemotherapy can dramatically improve both the quality and duration of survival. Ongoing developments in surgical techniques and technologies, radiotherapy and targeted chemotherapy options continue to improve the outlook for patients such as the gentleman presented here.

References
1. Bach F, Larsen BH, Rohde K, et al. Metastatic spinal cord compression.
Occurrence, symptoms, clinical presentations and prognosis in
398 patients with spinal cord compression. Acta Neurochir (Wien).
1990;107:37-43.
2. Ortiz Gómez JA. The incidence of vertebral body metastases. Int
Orthop. 1995;19:309-311.
3. Perrin RG. Metastatic tumors of the axial spine. Curr Opin Oncol.
1992;4:525-532.
4. Schiff D, O’Neill BP, Suman VJ. Spinal epidural metastasis as the
initial manifestation of malignancy: clinical features and diagnostic
approach. Neurology. 1997;49:452-456.
5. Tatsui H, Onomura T, Morishita S, et al. Survival rates of patients
with metastatic spinal cancer after scintigraphic detection of abnormal
radioactive accumulation. Spine. 1996;21:2143-2148.
6. Brihaye J, Ectors P, Lemort M, et al. The management of spinal
epidural metastases. Adv Tech Stand Neurosurg. 1988;16:121-176.
7. Constans JP, de Divitiis E, Donzelli R, et al. Spinal metastases with
neurological manifestations. Review of 600 cases. J Neurosurg.
1983;59:111-118.
8. Coleman RE. Skeletal complications of malignancy. Cancer
1997;80:1588-1594.
9. Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgery for
spinal metastases: clinical experience in 500 cases from a single
institution. Spine. 2007;32:193-199.
10. Ryu S, Rock J, Rosenblum M, et al. Patterns of failure after singledose
radiosurgery for spinal metastasis. J Neurosurg. 2004;101 Suppl
3:402-405.
11. Wright JL, Lovelock DM, Bilsky MH, et al. Clinical outcomes after
reirradiation of paraspinal tumors. Am J Clin Oncol. 2006;29:495-
502.
12. Yamada Y, Lovelock DM, Bilsky MH. A review of image-guided
intensity-modulated radiotherapy for spinal tumors. Neurosurgery.
2007;61:226-35; discussion 35.
13. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical
resection in the treatment of spinal cord compression caused by
metastatic cancer: a randomised trial. Lancet. 2005;366:643-648.
14. Klimo P Jr, Thompson CJ, Kestle JR, et al. A meta-analysis of
surgery versus conventional radiotherapy for the treatment of
metastatic spinal epidural disease. Neuro Oncol. 2005;7:64-76.
15. Yao KC, Boriani S, Gokaslan ZL, et al. En bloc spondylectomy
for spinal metastases: a review of techniques. Neurosurg Focus.
2003;15:E6.
16. Bilsky MH, Boland P, Lis E, et al. Single-stage posterolateral transpedicle
approach for spondylectomy, epidural decompression, and
circumferential fusion of spinal metastases. Spine. 2000;25:224-249,
discussion 250.
Disclosures
n J Bradley: j-2, Calypso Medical, Inc.
n J Buchowski: c-3, Styker, Inc.
n P Rose: nothing to disclose.