in the treatment of spinal tumors , radiotherapy is considered as the essential treatment modality5 ) . recently , stereotactic radiosurgery ( srs ) has been developed and widely used in the field of spine tumor treatment .
one of the major complications associated with srs is vertebral compression fracture ( vcf)3,7,11 ) . in cases of osteolytic spinal tumors , vertebral
body and pedicle are eroded by tumor mass and the remaining bony structures must withstand spinal loading . when radiation is delivered to spinal tumor and the remaining vertebral body ,
soft mass shrinkage and bony necrosis can develop , which leads to vcf and the resultant kyphotic deformity10 ) .
the risk of vcf following srs has been investigated in several studies . a prospective trial by rose et al .
revealed that 39% of treated vertebral bodies showed new or progressing fractures , in which larger , lytic lesions located in the lower spine presented a high risk11 ) .
larger radiation dose , previous spinal deformity , histology , age of more than 55 years and vertebral body involvement by at least 40 - 60% were suggested as significant risk factors3,7,12,13 ) . in cases of significant vcf , vertebroplasty or stabilization surgery
the spine oncology study group ( sosg ) defines spine instability as the " loss of spinal integrity as a result of a neoplastic process that is associated with movement - related pain , symptomatic or progressive deformity and/or neural compromise under physiological loads"8 ) .
the sosg developed the spinal instability neoplastic score ( sins ) in 20118,9 ) . under this classification system ,
tumor - related instability is assessed by adding together six individual component scores : spine location , mechanical pain , lesion bone type ( lytic or blastic ) , radiographic alignment , vertebral body collapse , and posterolateral involvement of the spinal elements ( table 1 ) .
a score of 0 - 6 means stable condition , 7 - 12 denotes indeterminate ( possibly impending ) instability , and 13 - 18 instability .
the study cohort was 72 patients with malignant spinal column tumors , who underwent srs ( table 2 ) .
the mean age of the participants was 51 years ( range , 19 - 78 years ) .
17 tumors were located in the cervical region , 26 in the thoracic region , and 29 in the lumbar spine .
pre - srs deformities such as compression fracture or kyphosis were present in 8 patients . spinal canal encroachment by tumor mass was observed in 22 patients .
sins ranged from 2 to 15 ( mean score=8 ) . a modified weinstein - boriani - biagini ( wbb ) classification system was adopted to assess the extent of tumor infiltration in the whole vertebral body4 ) ( fig .
this measure was developed specifically to stage in patients with primary spine tumors . in this system , the whole vertebral body including posterior element is divided into 12 sectors .
the rate of whole vertebral body involvement was defined as the ratio of the number of tumor - infiltrated sectors to whole sectors ( sector 1 - 12 ) .
vertebral body osteolysis rate is defined as the ratio of the number of tumor - infiltrated sectors to sectors 4 - 9 . to evaluate the extent of tumor infiltration , t1 weighted axial mri was used .
1b shows a tumor infiltrating both laminae , the right pedicle and right vertebral body , which correspond to sectors 8 - 12 , 1 , and 2 .
the sectors of vertebral body excluding posterior element are 4 - 9 . in fig .
when these values were calculated as single equivalent srs doses , they ranged from 18gy to 26gy ( mean=21gy ) .
after srs , patients were assessed with regular follow - up for pain status , neurological status and radiological response .
x - rays were checked every month for 3 months and mri was used to evaluate radiological response .
vcf was defined as development of a new fracture or progression of pre - existent fractures with relevant symptoms .
analyzed risk factors of vcf were age , sex , whole vertebral body involvement rate , vertebral body osteolysis rate , pre - srs spinal deformity , spinal instability neoplastic score ( sins ) , spinal canal encroachment , lesion level , and radiation dose .
continuous variables such as age , whole spine involvement rate , vertebral body osteolysis rate , sins and radiation dose were categorized as two groups ( below mean and above mean ) .
pre - srs spinal deformity and spinal encroachment were also analyzed as categorical factors , which mean the presence or absence of the factors .
the mean follow - up for the study population was 11 months ( range , 3 - 24 months ) .
the mean time to fracture for those patients who developed vcf was 1.5 months ( range , 0.3 - 3.5 months ) . according to uni - variate analyses ,
whole vertebral body involvement rate ( p=0.007 ) , pre - srs deformity ( p=0.013 ) , vertebral body osteolysis rate ( p=0.001 ) , and sins ( p=0.002 ) were significant factors ( table 4 ) .
however , multi - variate analyses confirmed that only vertebral body osteolysis rate was predictive of vcf development ( p=0.016 ) .
patients whose vertebral body was destroyed by more than 60% showed an 8.4 times higher risk of vcf than those who had vertebral body destruction of less than 60% .
pre - srs deformity ( p=0.31 ) , sins ( p=0.07 ) , and whole vertebral body involvement rate ( p=0.8 ) were not significant predictive factors .
ten patients underwent percutaneous vertebroplasty and 5 underwent fusion surgery to treat pain associated with post - srs vcf .
mri showed a metastatic spine tumor infiltrating c2 vertebral body , left pedicle and left lamina ( fig .
after srs , his pain improved and vcf was not detected at 24 months follow - up . in case 2 , the metastatic spine tumor involved the vertebral body only ( fig .
following srs , the neck pain aggravated and follow - up x - ray showed progression of kyphosis at the c2 - 3 level .
srs is an emerging treatment for spinal tumors and is widely applied in clinical setting .
although the risk of vcf is approximately 5% after conventional radiotherapy , crude risk estimates for vcf after spinal srs range from 11% to 39%13 ) .
the incidence of vcf reported after spinal srs is variable depending on the reporting authors .
, who reported vcf in 27 ( 39% ) of 71 sited treated with srs11 ) .
they treated patients with high - dose single fraction srs ( median dose-24gy in one fraction ) .
authors from md anderson cancer center investigated 127 vertebral bodies of 93 patients , and reported a 20% risk of vcf with a threemonth median time to vcf3 ) .
cunha et al . analyzed 167 spinal segments in 90 patients treated with srs and reported an actuarial vcf rate of 12.7% at 1 year post - srs with a mean time to vcf of 3 months7 ) . in this study , patients with srs of 20gy or greater were at a higher risk of vcf . in a recent study by sahgal et al .
, the approximate risk was 14% , and the 1-year cumulative incidence was 12.35%12 ) . in that report , it was clear that as the radiation dose increases , the risk of vcf significantly increased .
the incidence of vcf was 39% in the group with radiation doses of > 24gy .
the risk of late normal tissue adverse effects increases as the radiation dose increases . similar findings that doses > 20 gy are associated with a greater risk of radiation necrosis have been obtained from brain radiosurgery14 ) . in the present study ,
the incidence of vcf was 36% , which was higher than the risk reported by other authors .
several reports on post - srs vcf suggest that if the radiation dose is reduced , the adverse events associated with vcf can be avoided .
the present findings suggested whole vertebral body involvement rate , pre - srs deformity , vertebral body osteolysis rate , and sins as risk factors for vcf , using uni - variate analyses .
of these factors , vertebral body osteolysis rate was the only significant factor using multi - variate analyses .
in their study , risk factors of vcf included age > 55 years , a preexisting fracture , and baseline mechanical pain3 ) .
states that the presence of kyphotic / scoliotic deformity , presence of a lytic tumor , specific histology ( lung and hepatocelluar carcinoma metastasis ) , and radiation dose of 20 gy were predictive factors of vcf .
investigated the risk factors of vcf using six criteria of sins ; location , presence of mechanical pain , bone lesion type , alignment , baseline vcf , and posterior element involvement . among six criteria , baseline vcf , bone lesion type ( lytic tumor ) , and malalignment were significant factors
however , the overall score was not predictive , which is compatible with our present results .
another study by cunha et al . , which also evaluated sins criteria as predictive risk factor of vcf , revealed that the presence of a lytic tumor , and the presence of malalignment were significant and baseline vcf was excluded7 ) .
's study investigated the risk of fracture depending on the degree of the vertebral body involvement rate .
classification according to the amount of the vertebral body occupied by the lesion resulted in a significantly different fracture incidence .
the risk of vcf was 22% in the group with 1 - 20% vertebral body involvement , 58% in the group with 21 - 40% involvement , 86% in the patients with 41 - 60% involvement , and 83% in the patients with 61 - 80% involvement .
there were a significant difference in the risk of vcf between the group with vertebral body involvement < 40% and the group with vertebral body involvement > 40% , which is compatible with the results of the present study .
our data indicate that patients with vertebral body osteolysis rates more than 60% showed higher risk of vcf than those with rates less than 60% .
osteoradionecrosis , which lead to both healthy vertebral bone and tumor tissue being replaced with friable necrotic tissue , is the proposed mechanism of srs induced vcf .
osteoradionecrosis has been defined as a slow - healing radiation - induced ischemic necrosis of the bone tissue .
the mechanism of osteoradionecrosis is thought to relate to radiation therapy by the production of a hypoxic , hypocellular , and hypovascular environment in which the basic metabolic demands for cellular survival can not be met15 ) .
the onset of osteoradionecrosis has been described to range from 6 months to 3 years following treatment , and may even occur as late as 25 years after radiation therapy . in srs planning , the entire vertebral body is included in the target volume , even if focal involvement was diagnosed6 ) .
recent data have confirmed a great risk of failure if the target is restricted to a visible tumor within the vertebral body .
therefore , both the healthy trabecular bone and tumor tissue are exposed to the high radiation dose .
histopathological analysis showed markedly thinned bone trabeculae , and the bone marrow was completely replaced by either dense fibrous tissue with focal lymphocytic inflammation or loose paucicellular fibrous tissue .
bone is a complex two - phase composite substance containing mineral ( hydroxyapatite ) and organic ( collagen ) components13 ) .
the mineral component gives strength and stiffness to bone tissue whereas the collagen part gives bone ductility , increasing the tissue toughness .
decreases in the strength , modulus , and toughness of the collagen network are associated with decline in bone strength . a high radiation dose damages collagen , which reduces bone toughness .
the mechanism of radiation - associated collagen damage might be an increase in the cross - link ratios2 ) .
ultimately , exposure to radiation progressively degrades the strength , ductility , and toughness of the bone tissue2 ) .
the management of vcf consisted of conservative treatment , bone cement augmentation , or surgical stabilization .
the proportion of patients who underwent vertebroplasty or surgery was 3/2711 ) , 10/253 ) , and 9/197 ) .
of these patients , percutaneous cement augmentation procedures were used more commonly ( 77% ) than spinal stabilization surgery ( 23% ) .
the choice of surgical intervention is determined by radiological finding of the spine . for example , vcf without kyphosis and without substantial posterior element involvement can be treated with a percutaneous cement augmentation procedure alone . by contrast , patients with kyphotic deformity or translation instability generally need a combination of vertebral augmentation and pedicle screw reconstruction .
additionally , the systemic status of the patient , tumor pathology , and extent of metastatic burden need to be carefully considered when deciding on surgical options . of the patients in this study ,
15 out of 26 patients with vcf were treated with vertebroplasty ( 10 patients ) and stabilization operation ( 5 patients ) .
vertebral body osteolysis rate more than 60% was the only significant risk factor for post - srs vcf demonstrated by our findings .
 objectivestereotactic radiosurgery ( srs ) is an emerging treatment modality for malignant spinal tumors . after srs 
 , some patients suffered from pain aggravation due to development of vertebral compression fracture ( vcf ) . in these cases 
 , surgery should be considered.methodsthis study consisted of 72 patients who underwent srs due to spinal tumors . in them , whether post - srs vcf developed or not was investigated . 
 we retrospectively analyzed their medical records and radiological imaging data . 
 vcf was diagnosed with x - ray and magnetic resonance imaging ( mri ) . 
 the incidence , time to development and risk factors for vcf were investigated . 
 age , sex , whole vertebral body involvement rate , vertebral body osteolysis rate , pre - srs spinal deformity , spinal instability neoplastic score ( sins ) , spinal canal encroachment , lesion level , and radiation dose were analyzed as potential risk factors . 
 a multi - variate logistic regression model was used for statistical analysis.resultsin our study population , vcf was observed in 26 patients ( 36% ) . 
 the mean time to vcf development was 1.5 months . using uni - variate analyses , the significant risk factors were pre - srs spinal deformity , sins , vertebral body osteolysis rate , and whole vertebral body involvement rate . 
 however , using multi - variate analyses , the only significant risk factor was vertebral body osteolysis rate . 
 the patients whose vertebral body was destroyed by more than 60% showed an 8.4 times higher risk of vcf than those who had vertebral body destruction of less than 60%(p=0.016).conclusionthe most significant prognostic factor for post - srs vcf was vertebral body osteolysis rate , rather than whole vertebral body involvement rate . 
 when more than 60% of the vertebral body was destroyed , the risk of vcf or spinal deformity was high . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION