Spinal Metastases In Patients Research Articles

Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial

Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443. Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years. SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. National Cancer Institute of the US National Institutes of Health.

Analysis of Prognostic Factors Relating to Postoperative Survival in Spinal Metastases

ObjectiveTo analyze the prognostic factors thought to be related with survival time after a spinal metastasis operation.MethodsWe retrospectively analyzed 217 patients who underwent spinal metastasis operations in our hospital from 2001 to 2009. Hematological malignancies, such as multiple myeloma and lymphoma, were excluded. The factors thought to be related with postoperative survival time were gender, age (below 55, above 56), primary tumor growth rate (slow, moderate, rapid group), spinal location (cervical, thoracic, and lumbo-sacral spine), the timing of radiation therapy (preoperative, postoperative, no radiation), operation type (decompressive laminectomy with or without posterior fixation, corpectomy with anterior fusion, corpectomy with posterior fixation), preoperative systemic condition (below 5 points, above 6 points classified by Tomita scoring), pre- and postoperative ambulatory function (ambulatory, non-ambulatory), number of spinal metastases (single, multiple), time to spinal metastasis from the primary cancer diagnosis (below 21 months, above 22 months), and postoperative complication.ResultsThe study cohort mean age at the time of surgery was 55.5 years. The median survival time after spinal operation and spinal metastasis diagnosis were 6.0 and 9.0 months. In univariate analysis, factors such as gender, primary tumor growth rate, preoperative systemic condition, and preoperative and postoperative ambulatory status were shown to be related to postoperative survival. In multivariate analysis, statistically significant factors were preoperative systemic condition (p=0.048) and postoperative ambulatory status (p<0.001). The other factors had no statistical significance.ConclusionThe factors predictive for postoperative survival time should be considered in the surgery of spinal metastasis patients.

Vertebral metastases reirradiation with volumetric-modulated arc radiotherapy

PurposeTo assess the feasibility, acute toxicity, clinical improvement, local control and survival for spinal metastatic patients re-irradiated using volumetric-modulated-arc-radiotherapy (VMAT). Methods and materialsBetween February 2009 and November 2010, 31 patients were treated. Surgery was performed in six before re-irradiation. The clinical target volume (CTV) was defined as the whole vertebrae with recurrence excluding the central section of spinal canal. Planning target volume was defined as CTV+0–5mm in the three directions. Dose was prescribed in order to have biological equivalent dose to the spinal cord from the two courses lower than 120Gy2 to 1cc of the volume. Clinical improvement, toxicity and recurrence were evaluated. All patients had back pain before treatment and 15 (48%) neurological deficit. ResultsClinical remission of pain was obtained in 29 patients (93%). Neurological improvement was observed in 73% of patients. No acute or late toxicities were recorded. No recurrence occurred. Median survival was 10months (range 6–24). At the last follow-up 19 patients (61%) were alive and 12 (39%) dead from systemic disease progression. The 1 and 2year survival were 55% and 35%, respectively. ConclusionIn patients with spinal metastases recurrence re-irradiation with VMAT is feasible and provides clinical benefit in most patients.

Inter-Rater Reliability between Musculoskeletal Radiologists and Orthopedic Surgeons on Computed Tomography Imaging Features of Spinal Metastases

The primary objective of this pilot study was to examine the inter-rater reliability in scoring the computed tomography (ct) imaging features of spinal metastases in patients referred for radiotherapy (rt) for bone pain. In a retrospective review, 3 musculoskeletal radiologists and 2 orthopedic spinal surgeons independently evaluated ct imaging features for 41 patients with spinal metastases treated with rt in an outpatient radiation clinic from January 2007 to October 2008. The evaluation used spinal assessment criteria that had been developed in-house, with reference to osseous and soft tissue tumour extent,presence of a pathologic fracture,severity of vertebral height loss, andpresence of kyphosis.The Cohen kappa coefficient between the two specialties was calculated. Mean patient age was 69.2 years (30 men, 11 women). The mean total daily oral morphine equivalent was 73.4 mg. Treatment dose-fractionation schedules included 8 Gy/1 (n = 28), 20 Gy/5 (n = 12), and 20 Gy/8 (n = 1). Areas of moderate agreement in identifying the ct imaging appearance of spinal metastasis included extent of vertebral body involvement (κ = 0.48) and soft-tissue component (κ = 0.59). Areas of fair agreement included extent of pedicle involvement (κ = 0.28), extent of lamina involvement (κ = 0.35), and presence of pathologic fracture (κ = 0.20). Areas of poor agreement included nerve-root compression (κ = 0.14) and vertebral body height loss (κ = 0.19). The range of agreement between musculoskeletal radiologists and orthopedic surgeons for most spinal assessment criteria is moderate to poor. A consensus for managing challenging vertebral injuries secondary to spinal metastases needs to be established so as to best triage patients to the most appropriate therapeutic modality.

Are intravertebral vacuum phenomena benign lesions?

We retrospectively reviewed plain radiographs from patients with four different diseases that can cause vertebral collapse: osteoporotic vertebral collapse, spinal infection, spinal metastasis, and multiple myeloma. The objective of the study was to find the percentages of intravertebral vacuum phenomena and vertebral collapse rates in the four groups. The vacuum phenomenon is often observed in osteoporotic compression fractures. However, these phenomena are rarely seen in spinal infection and malignant lesions. Whether the vacuum phenomenon is a benign indicator is not known. We retrospectively reviewed plain radiographs from four groups of patients, including 328 osteoporotic vertebral collapse patients, 317 spinal infection patients, 302 spinal metastasis patients, and 325 multiple myeloma patients. The pattern and occurrence rates of intravertebral vacuum phenomena and vertebral body collapse were analyzed. The occurrence rate of intravertebral vacuum phenomena in patients with osteoporotic vertebral collapse was approximately 18.9%. Only one case of intravertebral vacuum phenomena was observed in patients with spinal infection. Vacuum phenomena were not observed in patients with spinal metastasis. The occurrence rate of intravertebral vacuum phenomena in patients with multiple myeloma was 6.4%. The patterns of intravertebral vacuum phenomena were also analyzed. Intravertebral vacuum phenomena are common in patients with osteoporotic vertebral collapse. Most cases of intravertebral vacuum phenomena are of a benign nature. Moreover, intravertebral vacuum phenomena occur extremely rarely in patients with spinal infection. Such phenomena are also found in patients with multiple myeloma.

Predictors of Survival After Surgical Treatment of Spinal Metastasis

Surgery for spinal metastasis is a palliative treatment aimed at improving patient quality of life by alleviating pain and reversing or delaying neurologic dysfunction, but with a mean survival time of less than 1 year and significant complication rates, appropriate patient selection is crucial. To identify the most significant prognostic variables of survival after surgery for spinal metastasis. Chart review was performed on 200 surgically treated spinal metastasis patients at Stanford Hospital between 1999 and 2009. Survival analysis was performed and variables entered into a Cox proportional hazards model to determine their significance. Median overall survival was 8.0 months, with a 30-day mortality rate of 3.0% and a 30-day complication rate of 34.0%. A Cox proportional hazards model showed radiosensitivity of the tumor (hazard ratio: 2.557, P<.001), preoperative ambulatory status (hazard ratio: 2.355, P=.0001), and Charlson Comorbidity Index (hazard ratio: 2.955, P<.01) to be significant predictors of survival. Breast cancer had the best prognosis (median survival, 27.1 months), whereas gastrointestinal tumors had the worst (median survival, 2.66 months). We identified the Charlson Comorbidity Index score as one of the strongest predictors of survival after surgery for spinal metastasis. We confirmed previous findings that radiosensitivity of the tumor and ambulatory status are significant predictors of survival.

Prospective evaluation of spinal reirradiation by using stereotactic body radiation therapy

Stereotactic body radiotherapy for previously irradiated, progressive spinal metastases may be a viable option in selected patients. The authors review a prospective series of spinal metastasis patients reirradiated with stereotactic body radiotherapy. A total of 59 patients with 63 tumors of the spine were reirradiated with stereotactic body radiotherapy between 2003 and 2009. Spinal magnetic resonance imaging was performed both before treatment initiation and at regular follow-up intervals. Stereotactic body radiotherapy was delivered to a peripheral dose of 30 grays (Gy) in 5 fractions (6 Gy per fraction), or 27 Gy in 3 fractions (9 Gy per fraction). The National Cancer Institute Common Toxicity Criteria 2.0 and McCormick neurological function system were used to evaluate toxicity and neurologic status, respectively. Mean follow-up was 17.6 months. Actuarial 1-year radiographic local control and overall survival for all patients were both 76%. Of the tumors that progressed after stereotactic body radiotherapy, 13 (81%) of 16 patients had tumors that were within 5 mm of the spinal cord, and 6 of them eventually developed spinal cord compression. Toxicity was most commonly grade 1 or 2 fatigue. Two patients experienced mild to moderate radiation injury (lumbar plexopathy) while remaining independently ambulatory and pain free. Freedom from neurologic deterioration from any cause was 92% at 1 year. Reirradiation for progressive spinal metastases with stereotactic body radiotherapy results in good local control and limited toxicity. Initial surgery should be considered for tumors within 5 mm of the spinal cord. Radiation dose should be tailored for tumors near or invading the psoas muscle secondary to observed risk of lumbar plexopathy.

Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review.

Spinal metastasis is a problem that afflicts many cancer patients. Traditionally, conventional fractionated radiation therapy and/or surgery have been the most common approaches for managing such patients. Through technical advances in radiotherapy, high dose radiation with extremely steep drop off can now be delivered to a limited target volume along the spine under image-guidance with very high precision. This procedure, known as stereotactic body radiosurgery, provides a technique to rapidly treat selected spinal metastasis patients with single- or limited-fraction treatments that have similar to superior efficacies compared with more established approaches. This review describes current treatment systems in use to deliver stereotactic body radiosurgery as well as results of some of the larger case series from a number of institutions that report outcomes of patients treated for spinal metastatic disease. These series include nearly 1400 patients and report a cumulative local control rate of 90% with myelopathy risk that is significantly less than 1%. Based on this comprehensive review of the literature, we believe that stereotactic body radiosurgery is an established treatment modality for patients with spinal metastatic disease that is both safe and highly effective.

Stereotactic Body Radiotherapy Reirradiation for Recurrent Epidural Spinal Metastases

When patients show progression after conventional fractionated radiation for spine metastasis, further radiation and surgery may not be options. Stereotactic body radiotherapy (SBRT) has been successfully used in treatment of the spine and may be applicable in these cases. We report the use of SBRT for 60 consecutive patients (81 lesions) who had radiological progressive spine metastasis with epidural involvement after previous radiation for spine metastasis. SBRT was used with fiducial and vertebral anatomy-based targeting. The radiation dose was prescribed based on the extent of spinal canal involvement; the dose was 8 Gy×3=24 Gy when the tumor did not touch the spinal cord and 5 to 6 Gyx5=25 to 30 Gy when the tumor abutted the cord. The cord surface received up to the prescription dose with no hot spots in the cord. The median overall survival was 11 months, and the median progression-free survival was 9 months. Overall, 93% of patients had stable or improved disease while 7% of patients showed disease progression; 65% of patients had pain relief. There was no significant toxicity other than fatigue. SBRT is feasible and appears to be an effective treatment modality for reirradiation after conventional palliative radiation fails for spine metastasis patients.

Usefulness of 18F-Fluorodeoxyglucose PET for Radiosurgery Planning and Response Monitoring in Patients with Recurrent Spinal Metastasis

With the advancement and successful treatment of metastatic spinal cord disease, newer treatments are needed for the long-term survivors of recurrent disease. The lack of a standardized re-treatment regimen and the difficulty in delineating the tumor margins among patients who have received the treatment with metallic spinal fixation and conventional radiation are two of the challenges to be faced in recurrent metastatic spinal cord disease. In these patients, we applied hypofractionated stereotactic radiosurgery by defining the tumor margin with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Three consecutive recurrent spinal metastasis patients underwent the CyberKnife treatment (Accuray, Inc., Sunnyvale, CA) from March 2004 to July 2004. A three-fraction schedule was applied at approximately 24 hour intervals. One patient had sarcoma and the other two patients had breast cancer. All patients had received previous conventional radiotherapy after operation ranging from 30 Gy to 45 Gy. CT-based planning was corrected by the FDG-PET hyperuptake area with the help of nuclear medicine. The mass responses were followed not only by MRI but also by FDG-PET, which was taken prior to treatment, and at one and six months after the treatment. The changes in standard uptake value (SUV) of serial PET were taken as a measure of response. To evaluate the relative SUV changes from different pretreatment values, we set a reduction index (RI), which represents the ratio of SUV change to pretreatment SUV. No significant complications were noted during treatment with a mean follow-up of 13.3 months. The tumor volume on CT-based planning was 2.2 times larger than that of the CT-PET combined planning in case 1 of paraspinal muscle invasion. But the tumor volumes showed minimal changes in the other cases, in which the metastatic tumors were confined to the vertebral bodies. The SUV one month after treatment showed variable decreases and the RI ranged from 0.07 to 0.7. However, the SUVs at 6 months were well correlated with the clinical results. One patient showed marginal failure and the other two patients showed local control of the tumor, as their RI values were 0.65 and 0.87, respectively. To our knowledge, this is the first report using FDG-PET with radiosurgery in patients with recurrent spinal metastases hidden under metallic artifacts. The mass responses measured by SUV changes in FDG-PET correlated with the clinical results.

Cervical spinal metastasis: anterior reconstruction and stabilization techniques after tumor resection

In a review of the literature, the authors provide an overview of various techniques that have evolved for reconstruction and stabilization after resection for metastatic disease in the subaxial cervical spine. Reconstruction and stabilization of the cervical spine after vertebral body (VB) resection for metastatic tumor is an important goal in the surgical management of spinal metastasis. Generally, the VB defect is reconstructed with bone autograft or allograft, polymethylmethacrylate (PMMA), interbody spacers, and/or cages. In cases of PMMA-assisted reconstruction, internal devices are used to augment the fixation of PMMA. Stabilization is then achieved with anterior instrumentation, usually an anterior cervical locking plate. In some cases, posterior instrumentation may be necessary to supplement the anterior construct. Anterior cervical corpectomy followed by reconstruction and stabilization is an effective strategy in the management of spinal metastases in patients.

‘Internal bracing’ surgery in the management of solid tumor metastases of the thoracic and lumbar spine

In patients with thoracolumbar spine metastasis, surgery is aimed at patient healing only when patient has a good prognosis with long life expectancy. In patients with short life expectancy a less aggressive surgical approach of posterior decompression and stabilization could improve patient care and allow for neurological recovery. Thirty-two consecutive patients affected by symptomatic thoracolumbar spine metastases with short life expectancy and good Karnofsky index (50-70) were subjected to surgery and reviewed retrospectively. After tumor embolization, surgery consisted of posterior decompression and stabilization with laminar hooks in the dorsal spine, and laminar hooks or lumbar pedicle screws. Patient's Karnofsky Index, average survival, Frankel neurological status, and pain were recorded before and after surgery, together with surgery related complications. Primary tumors were breast carcinoma (nine patients), renal cell carcinoma (three), lung carcinoma (four), GI tract carcinoma (six), prostate carcinoma (two), carcinoma of the uterus (two), melanoma (three), and malignant tumors at other different sites (three). Average survival after surgery was 23 months, with highest survival rates in renal cancer and breast carcinoma patients, and poorest survival rates in lung and dedifferentiated carcinoma. Karnofsky index improved from average 61 to 72% post-operatively. After surgery patients experienced significant overall improvement of Frankel score and decrease of referred pain. Hospitalization stay was on average 10 days. Results showed that operative treatment of symptomatic spinal metastases in patients with poor prognosis and good general health status improves or preserves neurological function, allows for adjuvant treatments to be performed and has a role in improving general health status in most patients.

Early MR demonstration of spinal metastases in patients with normal radiographs and CT and radionuclide bone scans.

Forty patients with known primary tumor and progressive back pain, suspected of having spinal metastatic disease, underwent magnetic resonance (MR) examinations of the thoracic and lumbosacral spine. Conventional radiographs and CT scans of the spine were all normal. The radionuclide bone scans were equivocal. In 21 patients focal or diffuse vertebral MR abnormalities were detected. In nine patients the lesions were hypointense on T1 sequence, and the same lesions were demonstrated poorly or not at all on T2 and proton density sequences. In eight other patients the bone marrow metastases presented with strong signal intensity on T2 and were poorly or not at all demonstrated on T1 and proton density sequences. In three patients with multiple myeloma, the signal intensity pattern of the vertebrae was diffusely heterogeneous, with alternating small foci of strong and weak signals (a mosaic-like pattern). Following the MR studies, needle biopsy confirmed the malignancy in the 21 patients who had shown abnormalities. No correlation between the type of primary tumor and the signal intensity of the vertebral metastases was shown. Possibly the mosaic pattern shown in three of the multiple myeloma patients represents a special case.

Intradural Spinal Metastases in Patients with Posterior Fossa Brain Metastases from Various Primary Cancers

Intradural spinal metastases (ISM) are rare and primarily found associated with certain types of brain tumors like medulloblastoma. Their association with metastases to the brain has been recently described and seems to occur more frequently in posterior fossa lesions. We reviewed patients treated at Massachusetts General Hospital for posterior fossa brain metastases from various primary cancers, and evaluated the risk of concomitant or subsequent ISM. Of 104 patients, 10 developed ISM, with a 1-year actuarial risk of 25%. The risk was not significantly related to age, sex, histology, site of primary tumor or previous therapy. The study suggests that in patients with posterior fossa metastasis, particular attention should be paid to seeding via cerebrospinal fluid and drop metastases to the spinal cord.

The risk of intradural spinal metastases in patients with brain metastases from bronchogenic carcinomas

Intradural spinal metastases can develop following dissemination via the cerebrospinal fluid from various primary or secondary brain tumors. Since the risk of intradural spinal metastases has never been formally studied in patients with brain metastases, we reviewed patients with brain metastases from bronchogenic carcinomas and looked for the subsequent development of intradural spinal metastases. Of 160 consecutive patients, only 6 presented intradural spinal metastases, however none were among the 105 patients who had exclusively supratentorial metastases and all intradural spinal metastases were in patients who had lesions in the posterior fossa. In this group, the 1-year actuarial risk of having intradural spinal metastases was 2196 (p < .01 compared with patients who had supratentorial metastases). We could not find any other risk factor for intradural spinal metastases. Recommendations for the group of patients with increased risk of intradural spinal metastases are made.

Radiostrontium in the early diagnosis of bone metastases in patients with prostatic carcinoma.

The diagnostic value of external counting of radiostrontium in the early diagnosis of pelvic and lower spinal metastases in patients with prostatic carcinoma is described. Thirty-two patients with prostatic carcinoma were investigated for bone metastases by external counting of 85Sr. The method proved to be a sensitive and reliable way of detecting early osteoblastic osseous metastases. By external counting of 85Sr, an earlier detection of the metastases and a closer view of its dissemination was possible than by X-ray. Local elevation of the isotope uptake in bone in patients with prostatic carcinoma is highly indicative of metastasis, even though radiological examination does not reveal any abnormality.