Cumulative dose, toxicity, and outcomes of spinal metastases re-irradiation : Systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The aim of this study was to identify patient-, tumor-, or treatment-related factors which may affect disease-related outcomes of re-irradiation (reRT) in patients with previously irradiated vertebral metastases. METHODS: A computerized search of the literature was performed by searching for terms related to reRT and spinal metastases in MEDLINE, EMBASE, OVID, and the Cochrane database from 1995 to 2019. Studies including at least 10 patients who had received reRT at the same site of initial radiotherapy for vertebral metastases with localized external beam radiotherapy were included. To determine the pooled ≥G3 acute and late toxicity rate, pain relief, local control, and overall survival, a meta-analysis technique of single-arm studies was performed. RESULTS: Nineteen studies including 1373 patients met the inclusion criteria for this systematic review. The pooled pain relief, neurological improvement, 1­year local control, and 1­year overall survival rates were 74.3%, 73.8%, 78.8%, and 54.6%, respectively, with moderate to high heterogeneity among studies. No difference in heterogeneity was evidenced for pain relief or local control after omitting studies not using stereotactic body radiotherapy (SBRT) or studies delivering biologically effective dose (BED) < 45 Gy10, whereas heterogeneity for 1­year OS was lower after omitting studies not using SBRT and delivering BED < 45 Gy10. The pooled results of grade ≥ 3 acute and late toxicity were 0.4% (95% confidence interval: 0.1-1.2%) and 2.2% (95% confidence interval: 1.2-37%), respectively, with low heterogeneity among studies. CONCLUSION: While this systematic review confirmed that reRT is both safe and effective for treating patients with recurrent spinal metastases, it could not identify factors which may affect outcomes of reRT in this patient population.

Review of Palliative Radiation Therapy Patterns of Practice for Adrenal Metastases in British Columbia.

PURPOSE: The adrenal gland is a common site of metastasis in patients with advanced cancer, but it is rarely symptomatic. A subset of patients develop a complex pain syndrome with anorexia, nausea, and poorly localized visceral pain in the back, flank, or epigastric region. These symptoms can affect quality of life and are occasionally challenging to palliate. The role of palliative radiation therapy (PRT) in these patients is unclear. This population-based retrospective study evaluates PRT practices for patients with adrenal metastases and aims to describe treatment response and acute toxicity. METHODS AND MATERIALS: Patients who received PRT to an adrenal metastasis between the years of 1985 and 2015 were identified in a provincial database. Patient demographics, tumor factors, symptom burden, radiation therapy prescriptions, and response to treatment were collected. Variables were summarized using descriptive statistics. The Kaplan-Meier test was used to assess survival. Factors associated with clinical response were evaluated using univariate and logistic regression analysis. Factors associated with survival were evaluated using univariate and Cox proportional hazards model. RESULTS: One hundred patients who received 103 separate courses of PRT were identified. The majority had a lung primary (82%). The most common baseline symptoms were pain (90%) and gastrointestinal upset (13%). Prescriptions ranged from 600 cGy in a single fraction to 4500 cGy in 25 fractions. Seventy percent of patients experienced an improvement in pain (either a complete or partial response). Forty-three percent of patients developed acute toxicity from treatment. Median survival was 3 months. CONCLUSIONS: Compared with other anatomic sites, conventional PRT is uncommonly delivered to adrenal metastases. Despite heterogeneity in tumor histology and radiation therapy prescriptions, treatment was associated with an overall pain response of 70%. Prophylactic antiemetics to decrease radiation-induced nausea are required before treatment. Given the poor prognosis of this population, short fractionations are indicated.

Early response assessment of palliative conventional radiotherapy for painful uncomplicated vertebral bone metastases.

BACKGROUND: Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis. METHODS: Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR. RESULTS: Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P < 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS < 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002). CONCLUSIONS: Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

[A case of thyroid medullary carcinoma with multiple painful bone metastases successfully treated with strontium-89 chloride].

A 70-year-old man was diagnosed as thyroid medullary carcinoma with multiple bone metastases. He underwent total thyroidectomy and cervical lymph node dissection. After one year, the pain from his bone lesions was becoming severe. To relieve the pain, he was administered opioids and external-beam radiation therapy. However, he continued to have substantial multiple bone pain. We used combination therapy of strontium-89 chloride for the treatment of widespread multiple bone pain and external-beam radiation therapy for localized pain. That combination therapy was effective and improved the QOL of the patient. We used strontium-89 chloride four times within one year, and no serious side effects occurred during therapy. Our thoroughly investigated case suggests that strontium-89 therapy is one of the effective and safe therapies for patients with painful bone metastases of thyroid medullary carcinoma.

Malignant epidural spinal cord compression: the role of external beam radiotherapy.

PURPOSE OF REVIEW: Spinal cord compression is a common complication of metastatic malignancy. If not diagnosed and treated early when the patient is still able to ambulate, outcomes and survival are poor. The purpose of this study is to review treatment options for patients presenting with metastatic spinal cord compression and emphasize the importance of early diagnosis. This review also aims to highlight the need for ongoing research to improve patient outcomes. RECENT FINDINGS: Recent literature suggests that treatment choices should take into account overall patient prognosis and ambulation status at diagnosis. In particular, poor prognosis patients can be treated with short courses of radiation and longer courses of radiation may be associated with better local control and therefore should be considered for good prognosis patients. Patient prognosis can be estimated using validated scoring systems. MRI screening may be of benefit in selected patient groups deemed at high risk of developing spinal cord compression. SUMMARY: Despite being a common complication of metastatic bone disease, there is a paucity of high-level evidence to guide treatment practice. Current and future randomized trials are vital.

Multimodal approach to the management of metastatic epidural spinal cord compression (MESCC) due to solid tumors.

PURPOSE: To assess the impact of a multidisciplinary approach for treatment of patients with metastatic epidural spinal cord compression in terms of feasibility, local control, and survival. METHODS AND MATERIALS: Eighty-nine consecutive patients treated between January 2004 and December 2007 were included. The most common primary cancers were lung, breast, and kidney cancers. Ninety-eight surgical procedures were performed. Radiotherapy was performed within the first month postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. Nearly all patients (93%) had back pain before treatment, whereas major or minor preoperative neurologic deficit was present in 62 cases (63%). RESULTS: Clinical remission of pain was obtained in the vast majority of patients (91%). Improvement of neurologic deficit was observed in 45 cases (72.5%). Local relapse occurred in 10%. Median survival was 11 months (range, 0-46 months). Overall survival at 1 year was 43.6%. Type of primary tumor significantly affected survival. CONCLUSIONS: In patients with metastatic epidural spinal cord compression, the combination of surgery plus radiotherapy is feasible and provides clinical benefit in most patients. The discussion of each single case within a multidisciplinary team has been of pivotal importance in implementing the most appropriate therapeutic approach.

Percutaneous tumor curettage and interstitial delivery of samarium-153 coupled with kyphoplasty for treatment of vertebral metastases.

OBJECT: The object of this study was to investigate the use of a minimally invasive technique for treating metastatic tumors of the vertebral body, aimed at relieving pain, preventing further tumor growth, and minimizing the adverse effects of systemic use of samarium-153 ((153)Sm). METHODS: The procedure is performed in the same fashion as a kyphoplasty, using a unilateral extrapedicular approach under local anesthesia/mild general sedation, with the patient in the lateral decubitus position. The tumor is accessed as in a standard kyphoplasty. The side is chosen according to the location of the metastasis. Prior to inflation of the balloon the tumor is debulked by percutaneous curettage. Balloon inflation is carried out as per standard kyphoplasty in an attempt to create a larger space and reduce a possible kyphotic deformity. Three mCi of (153)Sm-EDTMP (ethylenediaminetetramethylenephosphonic acid) is then mixed with bone cement (polymethylmethacrylate) and injected into the void created by the balloon tamp. RESULTS: Twenty-four procedures were performed in 19 patients. There was reliable and reproducible delivery of the radiolabeled (153)Sm-EDTMP to the metastatic site, without spillage. The procedure was safe. There were no procedure-related complications. There was no hematological toxicity with the low doses of (153)Sm used. Pain improved in all patients. The long-term results related to tumor control continue to be investigated. CONCLUSIONS: Combined percutaneous debulking of confined vertebral metastases and administration of local (153)Sm is feasible and safe. Furthermore, this technique leads to immediate relief of cancer-related pain and may help prevent or slow down the progression of vertebral metastatic tumors.

Efficacy of percutaneous vertebroplasty combined with radiotherapy in osteolytic metastatic spinal tumors.

OBJECT: Vertebroplasty involves the percutaneous injection of polymethylmethacrylate into collapsed vertebral bodies due to hemangioma, osteoporosis, or malignant tumor. The purpose of this study was to evaluate the merits and efficacy of percutaneous vertebroplasty (PVP) combined with radiotherapy in treating patients with osteolytic metastatic spinal tumors (OMSTs). METHODS: Twenty-eight patients with OMSTs underwent PVP for the treatment of 72 vertebrae after administration of a local anesthetic or induction of general anesthesia for pain relief and spinal stabilization. Radiotherapy for suppressing tumor or inducing pain relief was performed immediately after PVP in 22 patients. Pain levels were assessed before and after the procedure by using a visual analog scale (VAS), and follow-up assessment was conducted at 1, 3, 6, and 9 months. On postoperative Day 3, marked-to-complete VAS score-based pain relief was achieved in 13 patients (48%) and moderate relief was demonstrated in 11 (41%). The mean VAS pain score was reduced from 8.2 to 3, and major complications were absent in all cases. Follow-up plain radiography was performed to assess vertebral column stability. Neither additional vertebral collapse in the treated vertebrae nor neurological deterioration was observed. CONCLUSIONS: Percutaneous vertebroplasty is a minimally invasive procedure and, when combined with radiotherapy, seems to be effective in providing pain relief and stabilization in patients with OMSTs.

Laser therapy: a randomized, controlled trial of the effects of low-intensity Nd:YAG laser irradiation on musculoskeletal back pain.

OBJECTIVE: To assess the effectiveness of low-intensity laser therapy in the treatment of musculoskeletal low back pain. DESIGN: A double-masked, placebo-controlled, randomized clinical trial. SETTING: A physical medicine and rehabilitation clinic. PARTICIPANTS: Sixty-three ambulatory men and women between the ages of 18 and 70yrs with symptomatic nonradiating low back pain of more than 30 days' duration and normal neurologic examination results. INTERVENTION: Subjects were bloc randomized into two groups with a computer-generated schedule. All underwent irradiation for 90 seconds at eight symmetric points along the lumbosacral spine three times a week for 4 weeks by a masked therapist. The sole difference between the groups was that the probes of a 1.06 microm neodymium:yttrium-aluminum-garnet laser emitted 542mW/cm2 for the treated subjects and were inactive for the control subjects. MAIN OUTCOME MEASURES: Subject's perception of benefit, level of function as assessed by the Oswestry Disability Questionnaire, and lumbar mobility. RESULTS: The treated group had a time-dependent improvement in two of the three outcome measures: perception of benefit and level of function. These results were most marked at the midpoint evaluation (p < .005, p < .01) and end of treatment (p < .017, p < .001) but tended to lessen at the 1-month follow-up (p < .10, p < .004). Lumbar mobility did not differ between the groups at any time. All tests were two-sample t tests with unequal variances. CONCLUSIONS: Treatment with low-intensity 1.06 microm laser irradiation produced a moderate reduction in pain and improvement in function in patients with musculoskeletal low back pain. Benefits, however, were limited and decreased with time. Further research is warranted.

The longer term effect of pulsed radiofrequency for neuropathic pain.

Pulse radiofrequency has been recently described as a technique to apply a relatively high voltage near a nerve but without the usual effects of a rise in temperature or subsequent nerve injury. In this set of case reports, the effect of pulsed radiofrequency (PRF) is described in patients with neuropathic pain syndromes which have been poorly controlled with other oral and invasive treatments. Whilst anecdotal, the results have been remarkable and should encourage further research into this technique. Observations from the basic science tend to support the concept that PRF may induce some sort of long-term depression in the spinal cord.

Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial.

A phase II trial was planned to investigate the feasibility of radiotherapy (RT) without steroids in 20 consecutive patients with metastatic spinal cord compression (MSCC), no neurologic deficits, or only radiculopathy, and no massive invasion of the spine at magnetic resonance imaging (MRI) or computed tomography (CT). Aiming at an early diagnosis, MRI or CT was prescribed for all cancer patients with back pain and osteolysis, even when there were no signs of neurologic spinal compression. All patients were given 30 Gy in 10 fractions over 2 weeks with no steroids. Back pain and motor capacity were the parameters adopted to verify response to RT. Sixteen of 20 patients (80%) were able to walk without support, and 14 (70%) had no radiculopathy. Seventeen of 20 cases (85%) achieved relief from back pain. Regarding motor function, all patients (100%) responded to RT because the 16 patients able to walk without support at diagnosis did not deteriorate and the other 4, who needed support, became ambulatory without motor impairment. Median survival time was 14 months. Eight of 20 (40%) treated patients are still alive (14 to 36 months after end of RT), fully ambulatory, and free from relapse in the treated spine. Acute side effects were documented in only 2 patients (10%) and were managed without steroids. The results of this study suggest that RT without steroids is a feasible regimen for MSCC patients with good motor function. Elimination of steroids from the standard treatment for MSCC avoids cortisone side effects above all in those patients with diabetes, hypertension, peptic ulcer, and other steroid-sensitive medical problems.

Targeted radiotherapy of osteosarcoma using 153 Sm-EDTMP. A new promising approach.

We report a case where targeted radionuclide therapy using 153Sm-EDTMP gave substantial palliative effect. A 35-year-old male with a primary osteosarcoma located in the first lumbar vertebra relapsed with progressive back pain after conventional treatment modalities had failed. He became bedridden, and developed paraparesis and impaired bladder function. On a diagnostic bone-scan intense radioactivity was localized in the tumor. He therefore was given 153Sm-EDTMP treatment twice, 8 weeks apart, 35 and 32 MBq/kg body weight respectively. After a few days the pain was significantly relieved and by the second radionuclide treatment the pareses subsided. For six months he was able to be up and about without any neurological signs or detectable metastases. Eventually, however, he experienced increasing local pain, developed paraparesis, was re-operated but died 4 months later. The dramatic transient improvement observed in this case warrants further exploration using 153Sm-EDTMP as a boost technique, supplementary to conventional external radiotherapy.

[Tuberculous spondylitis--a forgotten differential diagnosis in backache]. / Spondylitis tuberculosa--eine vergessene Differentialdiagnose bei Rückenschmerzen.

A four-year-old boy had been complaining for one year of backache when sitting or bending. Radiological changes in the lumbar spine were at first interpreted as due to an old vertebral fracture. Half a year after the onset of the symptoms his sister was found to have open pulmonary tuberculosis, but a positive Tine test (he had not received BCG vaccination) was without any consequences. He was finally hospitalized five months later because the backache persisted and he now also had impaired movement of the left hip-joint. Physical examination revealed a 10 x 15 cm firm mass in the abdomen. Imaging demonstrated destruction of the 4th and 5th lumbar vertebrae and a large abscess. Acid-fast bacteria were found in gastric juice. Tuberculostatic treatment was started with isoniazid (10 mg/kg), rifampicin (10 mg/kg) and pyrazinamide (30 mg/kg). Two weeks later spondylectomy was performed, the defect being bridged with bone chips from the iliac crest. Four months after the operation, tuberculostatic treatment now being only isoniazid and rifampicin, he was able to partake fully in all activities of his age group.

Systemic mastocytosis--a case treated with interferon alpha and radiotherapy.

Systemic mastocytosis is uncommon. Symptoms result from local infiltration and degranulation of mast cells. Reports in the literature describe successful use of interferon alpha and radiotherapy to produce reduction in symptoms and bulk of disease. We report a patient who responded to radiotherapy but not interferon alpha.

Clinical study of the effect of laser therapy in rheumatic degenerative diseases.

The effect of a 940-980 nm length wave laser radiation in rheumatic degenerative diseases was studied in 136 patients unresponsive to or with contraindications for antiinflammatory non-steroid therapy. The evolution was clinically estimated using four parameters; pain, muscular contracture, local edema and the impairment of the articular mobility. All patients presented a beneficial evolution appearing gradually during the treatment. The osteoarthritis of the knee, ankle and shoulder evolved worse than the painful back. The painful back presented an improved evolution when it was located at the thoracal level. No adverse reaction was observed during this study.

Spinal epidural tumor in patients with prostate cancer. Clinical and radiographic predictors of response to radiation therapy.

The authors retrospectively reviewed 50 episodes of spinal epidural tumor that occurred in 42 patients with metastatic prostate cancer and were treated with external-beam radiation. Treatment response was evaluated in terms of symptoms, neurologic status, and, in most cases, reduction of tumor on repeat myelography. At the completion of therapy, 92% of treated patients experienced pain relief and 67% had significant to complete improvement on neurologic examination. Thirty days after treatment, repeat myelography was performed in 40 of the 50 cases; compared with the initial findings immediately preceding radiation therapy (RT), the results of 58% of these studies had normalized completely, results were improved in 25%, and the results had not changed in 18%. The presence of a high-grade compression fracture of the vertebral body was an indicator of poor prognosis for tumor response on repeat myelography. The ability of a patient to walk before treatment and tumor response on repeat myelography were associated significantly with improved outcome of RT and with survival. The authors conclude that RT can effectively palliate epidural lesions from metastatic prostate cancer. The prognosis for the long-term response to therapy may be indicated by pretreatment ambulatory status and posttreatment imaging of the epidural space.

Radiation therapy in a case of systemic mastocytosis: evaluation of histamine levels and mucosal effects.

Plasma histamine levels were obtained during palliative radiation therapy of the spine involved with systemic mastocytosis in a 68-year-old woman. Baseline plasma histamine levels were obtained before irradiation and compared to levels obtained on the third, fifth, eighth, and tenth treatment days. Despite concerns regarding histamine release with mast cell destruction following irradiation, plasma histamine levels remained within normal limits. No change in dermatologic or other systemic manifestations were observed. No untoward systemic or localized sequelae associated with mast cell degranulation in response to the administered large field of radiation was observed. Effective palliation was accomplished, and it was concluded that radiation therapy can effectively be applied in treatment of systemic mast cell disease without significant morbidity.