High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions
To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT.
A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging.
The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed.
High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
Available from: trialsjournal.com
- "The aim of this trial is to test the hypothesis that stereotactic radiotherapy gives a better and longer lasting reduction of pain, better local control, and therefore a better quality of life without an increase of treatment-related side effects compared to conventional radiotherapy for symptomatic spinal metastases. Recent trials and reports using SBRT show excellent local control and a fast pain reduction in 1 to 2 weeks when treating painful spinal metastases [8, 10, 11,2223242526. In recent years, systemic therapies have improved significantly, resulting in a better median survival of incurable patients, that is, with metastasized disease. "
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ABSTRACT: Painful spinal metastases have been treated with conventional radiotherapy for decades, but one-third of the patients have insufficient pain relief after treatment and one-fifth need retreatment. Stereotactic radiotherapy is a method to increase the dose in the spinal metastases with a potentially longer lasting palliative effect without increasing the side effects of the treatment and thereby is expected to improve the quality of life significantly.
This study is a multicenter prospective randomized clinical trial comparing conventional radiotherapy (1 x 8Gy) with stereotactic radiotherapy (1 x 20Gy) for pain reduction and quality of life in patients with painful spinal metastases. A total of 386 patients will be randomized between the two treatment groups. Besides pain measured by the Dutch Brief Pain Inventory, quality of life and cost-effectiveness also will be measured. The primary outcome is pain reduction at 6 weeks after treatment. Secondary outcomes will be the time to pain response, duration of pain relief, health-related quality of life and toxicity, as well as cost-effectiveness.
This study investigates whether stereotactic radiotherapy with dose escalation for symptomatic spinal metastases can lead to improved pain reduction as compared to conventional radiotherapy without an increase of treatment-related side effects. These results will contribute to the optimization and individualization of the treatment for the patient.
ClinicalTrials.gov identifier NCT02407795 (March 31, 2015).
Available from: Bronek Boszczyk
- "The development of stereotactic radiosurgery (SRS) for the spine has improved local control rates compared with conventional radiotherapy. However, despite the promise shown with SRS   , the availability of this modality is currently limited in the United Kingdom. "
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ABSTRACT: BACKGROUND CONTEXT: The surgical treatment in spinal metastases has been shown to improve function and neurological outcome. Unplanned hospital readmissions can be costly and cause unnecessary harm. PURPOSE: Our aim was to firstly analyse the re-operation rate and indications for this revision surgery in spinal metastases from an academic tertiary spinal institute and secondly, to make comparisons on outcome (neurology and survival) against patients who underwent single surgery only. STUDY DESIGN/SETTING: An ambispective review of all patients treated surgically over 8 year period considering their neurological and survival outcome data. Statistical analysis was performed using IBM SPSS 20. Since all scale values did not follow the normal distribution and significant outlier values existed, all descriptive statistics and comparisons were made using median values and the Median test. Crosstabs and Pearson's correlation were used to calculate differences between percentages and ordinal/ nominal values. For two population proportions the Z Test was used to calculate differences. The Log Rank Mantel-Cox analysis was used to compare survival. PATIENT SAMPLE: During the 8 years' study period, there were 384 patients who underwent urgent surgery for spinal metastasis. Of these, 289 patients were included who had sufficient information available. There were 31 re-operations performed (10.7%; mean age 60 years; 13M, 18F). Exclusion criteria included patients treated solely by radiotherapy, patients who had undergone surgery for spinal metastasis prior to the study period and those patients who had other causes for neurological dysfunction such as stroke. OUTCOME MEASURES: Revised Tokuhashi score, preoperative/postoperative Frankel scores and survival. METHODS: We performed an ambispective review of all patients treated surgically from our comprehensive database during the study period (October 2004-October 2012). We reviewed all patient records held on the database, including patient demographics and re-operation rates. RESULTS: During the 8 years' study period, there were 31 re-operations performed (10.7%; mean age 60 years; 13M, 18F) in the 289 patients. Re-operations were performed in the same admission in the majority of patients (20), whilst 11 patients had their second procedure in subsequent hospitalisation. The reasons for their revision surgery were as follows: Surgical Site Infection (SSI) [13/31, (42%)], failure of instrumentation [9/31, (29%)], local recurrence [5/31, (16%)], haematoma evacuation [2/31, (6%)] and others [2/31, (6%)]. When comparing the 'Single Surgery' and 'Revision Surgery' groups, we found that the median preoperative and postoperative Frankel scores were similar at grade 4 (range: 1- 5) for both groups (preoperative p= 0.92, postoperative p=0.87). However, 20 (8%) patients from the Single surgery group and 7 (23%) from the Revision group had a worse postoperative score and this was significantly different (p=0.01). No significant difference was found (p=0.66) in the revised Tokuhashi score. The median number of survival days was similar (p=0.719) - Single Surgery Group (250 days, range: 5- 2597) and Revision Group (215 days, range: 9-1352). CONCLUSION: There was a modest re-operation rate (10.7%) in our patients treated surgically for spinal metastases over an 8 year period. Most of these were for SSI (42%), failure of instrumentation (26%) and local recurrence (16%). Patients with metastatic disease could benefit from revision surgery with comparable median survival rates but relatively poorer neurological outcomes. This study may help to assist with informed decision making for this vulnerable patient group.
Available from: PubMed Central
- "Centrally located lung tumors, being more prone to normal tissue toxicity than peripheral tumors, may gain similar numbers of tumor control (>85%) and acceptable toxicity with a less potent dose per fraction, i.e., eight fractions of 7.5 Gy (32, 33). In addition to lung cancers, SART (15–18 Gy × 3) has also generated encouraging results in primary and secondary (34, 35) hepatic tumors (36–38) and metastatic spinal lesions (39, 40). "
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ABSTRACT: Ionizing radiation is a non-specific but highly effective way to kill malignant cells. However, tumor recurrence sustained by a minor fraction of surviving tumor cells is a commonplace phenomenon caused by the activation of both cancer cell intrinsic resistance mechanisms, and also extrinsic intermediaries of therapy resistance, represented by non-malignant cells and structural components of the tumor stroma. The improved accuracy offered by advanced radiotherapy (RT)-technology permits reduced volume of healthy tissue in the irradiated field, and has been triggering an increase in the prescription of high-dose oligo-fractionated regimens in the clinics. Given the remarkable clinical success of high-dose RT and the current therapeutic shift occurring in the field, in this review we revise the existing knowledge on the effects that different radiation regimens exert on the different compartments of the tumor microenvironment, and highlight the importance of anti-tumor immunity and other tumor cell extrinsic mechanisms influencing therapeutic responses to high-dose radiation.
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