- 2009

Tumor-related neurologic complications

Epidural cord compression Increased intracranial pressure Leptomeningeal metastases

Therapy-related neurologic complications

After radiation therapy After chemotherapy

Radiotherapy spinal cord complications

Lhermittes sign transient electric shock-like sensations with neck flexion delayed progressive myelopathy motor-neuronal syndrome


Epidural spinal-cord compression (ESSC) can be dened as the compressive indentation, displacement, or encasement of the thecal sac that surrounds the spinal cord or cauda equina by spinal epidural metastases (SEM) or by locally advanced cancer


1520 percent of patients with cancer develop neurologic complications during the course of their illness The incidence of neurologic complications of cancer is increasing in frequency as the disease is being controlled for longer periods of time producing an increased opportunity for metastases to the nervous system or result from treatments such as chemotherapy, biologic, or radiation therapy

,
Lung tumors breast tumors prostate tumors

Primary sites of tumors causing cord compression

(adapted from Fuller et al.) Tumor type Frequency (%) Breast 29 Lung 17.2 Prostate 14.2 Lymphoma 5.0 Renal 4.2 Myeloma 4.0 Other 24

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Causes of spinal cord dysfunction in patients with cancer

(from Quinn and DeAngelis et al.)
Epidural cord compression (ECC)
Tumor Abscess Hematoma Disc herniation Vertebral hemangioma Metastases Abscess Hematoma Syrinx Radiation Intrathecal chemotherapy Paraneoplastic

Intramedullary process

Myelopathy

Leptomeningeal metastases Spinal arachnoiditis

Epidural spinal cord compression

Compression of the thecal sac by tumor in the epidural space. This compression occurs either at the levels of the spinal cord or cauda equina. Epidural cord compression occurs in 514 percent of patients with cancer.

Localization of the epidural spinal cord compression

Cord compression most commonly occurs at the thoracic spine (5978 percent) lumbosacral (2143 percent) cervical spine (415 percent)

Tumor causes cord compression in one of three ways

hematogenously disseminated metastasis to a vertebra erodes into the epidural space (85 %) paravertebral tumors gain access to the epidural space via the intervertebral foramina (1012 %) direct metastasis to the epidural space (1 3 %)


In patients who are ambulatory at the start of therapy 80 percent will remain so after therapy only 5 percent of paraplegic patients are ambulatory after treatment

Thus any patient with a known malignancy and new back pain should have at least a plain X-ray of the affected area

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the rapidity of neurologic decline, duration of neurologic decline, most importantly, neurologic status before treatment


First symptom of spinal cord compression
(adapted from DeAngelis and Posner)

Neurologic signs and symptoms of spinal cord compression at diagnosis

(adapted from Fuller et al.)

Signs and symptoms

Percentage of patients (%) Signs and symptoms Percentage of patients (%)

Pain 94 Weakness 3 Ataxia 2 Sensory loss 0.5 Autonomic dysfunction 0

Pain Weakness Sensory dysfunction Autonomic dysfunction

91 79 67 49


Over 85 percent of cord compressions due to solid tumors will have an abnormal spine radiograph X-rays and CT: vertebral body erosion vertebral body collapse subluxation pedicle erosion If the cord compression is via the intervertebral foramina there may not be an abnormal spine radiograph or bone scan.


The entire spine should be imaged because of the high incidence of asymptomatic multilevel disease (2049 percent). A definitive diagnosis requires a T2weighted MRI that shows a mass impinging on the thecal sac


MRI is the best diagnostic tool for cord compression If the cord compression is via the intervertebral foramina there may not be an abnormal spine radiograph or bone scan. The entire spine should be imaged because of the high incidence of asymptomatic multilevel disease (2049 percent). A definitive diagnosis requires a T2-weighted MRI that shows a mass impinging on the thecal sac


Initial growth of the cancer in the vertebral body causes local pain as a result of the stretching of the periosteum. Further growth compresses adjacent neural and vascular structures causing neurologic signs and radicular pain


Steroid Medications - Dexamethasone is the most widely (reduce
vasogenic edema, protect against lipid peroxidation and lipid hydrolysis, prevent ischemia and intracellular calcium accumulation, and support cellular energy metabolism)

Radiation
Conventional Radiation therapy Nonconventional Radiation Therapy
stereotactic radiosurgery (SRS) is usually delivered in one or two sessions, with total doses ranging from 8001,800 cGy intensity-modulated radiotherapy (IMRT)

Surgery
Posterior Decompressive Laminectomy Circumferential Spinal Cord Decompression Minimally invasive spinal surgery (MISS) Percutaneous vertebroplasty and kyphoplasty

Indications to radical surgical treatment

radioresistant tumors (sarcoma, lung, colon, renal cell), obvious spinal instability, or bone fragments contributing to pain or neurologic findings clinically significant neural compression secondary to retropulsed bone or from spinal deformity intractable pain unresponsive to nonoperative measures, radiation failure (progression of deficit during treatment or spinal cord tolerance reached) no prior history of cancer high cervical location single site epidural/spinal cord compression

Goals of surgery
to correct and prevent any further deformity by stabilizing the spine, decompressing neural structures (spinal cord and nerves), obtaining a diagnosis if the primary is unknown, preventing local recurrence.


Even if the patient satisfies one or more of the above indications, the type and goals of surgery must be determined by the patients ability to tolerate the procedure (i.e., the patients general medical condition) and, more importantly, by their estimated life expectancy


Excisional surgery should only be offered to those patients with an estimated life expectancy of greater than 3 months The mortality ranges from 6 to 10 percent.


Patients with Karnofsky scores of 80100 and modified Tokuhashi scores less than 2 had the highest survival times. When deciding upon surgery, the Karnofsky score should be taken into consideration if the modified Tokuhashi score is less than 2. If the general condition is not good (Karnofsky < 40%, modified Tokuhashi > 5), then palliative treatment modalities should be considered.


Patients who have scores 5 generally die within 3 months whereas those with total scores 9 survive an average of 12 months or more. Several others, including the authors, have used this scoring system and have found it useful in making decisions regarding treatment

Karnofsky performance status scale

Score 100 90 80 70 60 50 40 30 20 10 0 Criteria Normal, no complaints, no evidence of disease Able to carry on normal activity, minor signs and symptoms Normal activities with effort, some signs or symptoms Care for self, unable to carry on normal activity or do active work Requires occasional assistance, cares for most needs Requires considerable assistance and frequent care Disabled, requires special care and assistance Severely disabled, hospitalized, death not imminent Very sick, hospitalized, active supportive care needed Moribund, fatal processes are progressing rapidly Dead

Tokuhashi preoperative prognostic scoring

system

Characteristics General health condition Extra-spinal bone metastasis Other vertebral metastasis Other visceral organ metastasis Primary site of the cancer Palsy Score good = 0, bad = 1 no = 0 , yes = 1 no = 0, yes = 1 no = 0, yes = 1 limited = 0, diffuse = 1 normal = 0, paresis = 1, plegia = 2

Decompressive laminectomy
quick and simple procedure limited value in regaining neurologic function pain control rather than neurologic rescue laminectomy with adjuvant radiation was no more effective than radiation alone in retaining or restoring ambulatory function complications associated with laminectomies, - the acceleration of preexisting spinal instability - wound complications

Decompressive laminectomy is indicated in only three situations

1) to establish a diagnosis; 2) to treat a relapse if the patient is unable to undergo further radiation therapy; 3) if symptoms progress during radiation treatment.


Thus, conventional external beam radiotherapy became and continues to be the first-line treatment in the majority of patients with newly diagnosed metastatic spinal disease.

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Circumferential Spinal Cord Decompression

a new treatment protocol

Surgical approaches to the spine

. A) Laminectomy. The spinous process and the adjacent lamina are removed up to the junction of the pedicles. It can still be used for disease isolated to the posterior elements. B) Transthoracic or retroperitoneal. These anterior approaches provide direct access to the vertebral body in the thoracic (transthoracic) and thoracolumbar/lumbar regions (retroperitoneal). C) Posterolateral. For patients who cannot tolerate an anterior approach or who have significant posterior extension of their disease, a posterolateral approach provides excellent access to both the anterior and posterior elements. The laminectomy (A) and posterolateral (B) approaches can be performed through a midline incision. The transthoracic (upper B line) and retroperitoneal approaches (lower B line) require flank incisions.

Circumferential Spinal Cord Decompression The goal of surgery

to excise the tumor, reconstruct the spinal column, place internal fixation devices to achieve immediate stabilization. to achieve circumferential spinal cord decompression. This requires removing the tumor at the site of spinal cord compression

American Society of Clinical Oncology,

Patchell, et al., 2003

the results of randomized, controlled trial

50 patients in the surgical arm and 51 in the radiation arm Patients treated with surgery retained ambulatory and sphincter function significantly longer than patients in the radiation group. Also, 56% of nonambulatory patients in the surgical group regained the ability to walk, compared with 19% in the radiation group. Survival was not significantly different between the two groups.

Circumferential Spinal Cord Decompression

Use of these surgical techniques, usually followed by standard radiation therapy success" rate was 85%, with "success" defined as the percentage of patients retaining or regaining ambulatory. "rescue" rate from the same series, defined as the percentage of patients who regained ambulatory function, was 60% success rate of 73% and a rescue rate of 29% in the most recent conventional radiation reports

Circumferential Spinal Cord Decompression undisputed advantage for surgery, where the goal is to achieve complete spinal cord decompression, over radiation therapy, which has been the treatment of choice for the last 25 years.

Postoperative prognosis according to the primary lesion

Patients with breast and renal cell carcinoma both had median survival times of 36 months, compared with 15 months and 12 months for gastrointestinal and unknown primary carcinomas, respectively
Sundaresan N, Rothman A, Manhart K et al. Surgery for solitary metastases of the spine. Rationale and results of treatment. Spine 2002;27:18021806

Indications for radiotherapy

radiosensitive tumors (lymphoma, multiple myeloma, small-cell lung carcinoma, seminoma of testes, neuroblastoma,and Ewing sarcoma); expected survival less than 3 or 4 months; patient unable to tolerate an operation; total neurological deficit below the level of compression for more than 24 to 48 hours; multilevel or diffuse spinal involvement

Factors associated with wound infection

postoperative incontinence, posterior approach, surgery for tumor resection, morbid obesity preoperative radiation (especially within 7 days), malnutrition, steroids

Minimally invasive spinal surgery (MISS)

shorter operative times, less blood loss, less postoperative pain, lower medication use, shorter hospital stays, lower overall costs.

Minimally invasive spinal surgery (MISS)

The three phases of the surgery vertebrectomy, reconstruction, and stabilizationcan be performed entirely by endoscopic techniques.

Percutaneous vertebroplasty and kyphoplasty

injection of polymethylmethacrylate bone cement (PMMA) into a collapsed vertebral body In vertebroplasty, the vertebral body is not re-expanded, whereas in kyphoplasty, a balloon is first inflated, thereby restoring the vertebral body height and reducing kyphosis, followed by injection of PMMA Poor surgical candidates with disabling pain secondary to a pathologic thoracic or lumbar vertebral body fracture without epidural compression are ideal candidates for the procedure. The procedure is quick, performed on an outpatient basis, rarely associated with complications, and highly effective in reducing axial spinal pain

Percutaneous vertebroplasty and kyphoplasty indications

Poor surgical candidates Disabling pain secondary to a pathologic thoracic or lumbar vertebral body fracture Absence of epidural compression

Percutaneous vertebroplasty and kyphoplasty

A) The collapsed vertebral body is accessed through a transpedicular route. In kyphoplasty, a balloon at the end of the instrument is inflated, thus restoring the height of the body. This step is not performed in vertebroplasty. B and C) The balloon is removed and the defect is filled with bone cement (PMMA), which reestablishes the structural integrity of the vertebral body.

Radiotherapy
Conventional external beam radiotherapy Nonconventional radiotherapy stereotactic radiosurgery (SRS) is usually delivered in one or two sessions, with total doses ranging from 8001,800 cGy Intensity-modulated radiotherapy (IMRT)

Conventional external beam radiotherapy

typically delivers a total dose of 2540 Gy of radiation over 820 daily fractions. Generous margins are used within the radiation field, typically one or two vertebral segments, to compensate for internal organ motion as well as patient motion during the treatment.

Stereotactic Radio Surgery

Current image-guided SRS systems, such as the Novalis system (BrainLAB Inc.; Munich, Germany) and CyberKnife (Accuray Inc.; Sunnyvale, CA), differ from earlier frame-based systems in four ways: A) referencing is based on internal skeletal anatomy, implanted fiducials, or infrared surface markers; B) near real-time images are acquired to correct for motion; C) fixed isocenters are not required, allowing irregular dose shapes, D) intensity modulation of radiation increases the conformality of radiation to the tumor while minimizing the dose of radiation to normal tissue

Stereotactic Radio Surgery

At this time, the application of spinal SRS is usually limited to patients who are poor surgical candidates with recurrent disease, and by the availability of the technology. Therefore, it should still be considered experimental therapy


surgery should be considered the primary treatment modality in all patients with newly diagnosed metastatic disease who do not have any of the indications for radiotherapy

Radiotherapy brain irradiation

Acute complications 1. acute encephalopathy 2. brain herniation Early complications 1. somnolence syndrome 2. symptoms simulating local recurrence 3. brain stem encephalopathy Delayed complications 1. radiation necrosis 2. cognitive dysfunction

Peripheral nerve irradiation

Radiation plexitis Plexopathy