Tumor pseudoprogression of spinal metastasis after radiosurgery: a novel concept and case reports

Abstract

<jats:p>Radiosurgery for primary and metastatic tumors of the central nervous system is increasing in utility and intensity. Known complications in the brain include radiation necrosis and the well-documented phenomenon of pseudoprogression. Known complications of radiosurgery to spinal column tumors include radiation myelopathy and delayed vertebral compression fractures; however, the concept of pseudoprogression of spinal column tumors has not been previously described. The authors review 2 cases of spinal metastasis treated with stereotactic radiosurgery (SRS) and attempt to define the concept of spine tumor pseudoprogression.</jats:p> <jats:p>Two patients who had undergone SRS to the spine for metastatic disease presented in early follow-up (3 and 7 weeks) with symptomatic complaints consisting of axial pain, radicular pain, or evidence of cord compression. In both patients, MRI revealed evidence of tumor enlargement. In one patient, the lesion had grown by 9 mm and 7.7 mm in the axial and sagittal planes, respectively. In the other patient, the tumor growth resulted in a 5-mm decrease in spinal canal diameter with epidural compression and right foraminal encroachment. Because of the absence of progressive neurological deficit, myelopathy, mechanical symptomatology of instability, or vertebral compression fracture, the first patient was treated expectantly with a corticosteroid taper and had improvement of symptoms at 1 month and near-total radiographic resolution of the tumor. In the second patient, worsening symptoms suggested a need for surgical intervention to address presumed radiosurgical failure and tumor progression. During surgery, only necrotic tumor cells were observed, without viable tumor. Follow-up imaging over 1 year showed ongoing local control.</jats:p> <jats:p>To their knowledge, the authors report the first description of pseudoprogression involving spinal column metastasis in the literature and aim to alert the treating physician to this clinical situation. Unlike brain tumor pseudoprogression, spine tumor pseudoprogression is a relatively early posttreatment phenomenon, measured in days to 2 months. The authors believe that the acute inflammatory response associated with tumor necrosis and disruption of the tumor capillary integrity caused by radiotherapy is an important component in the development of pseudoprogression. Future studies will be fundamental in assigning clinical significance, defining the incidence and predictors, and affecting future management of this phenomenon.</jats:p>

Osseous Pseudoprogression in Vertebral Bodies Treated with Stereotactic Radiosurgery: A Secondary Analysis of Prospective Phase I/II Clinical Trials

“…With expanded use of SBRT, pseudoprogression has been described and analyzed in lung lesions 5, 6 and more recently reported in the soft tissue components of two bone lesions following SSRS 7 . However, no systematic analysis or even anecdotal reports of pseudoprogression of lesions confined to bone have been published.…”

“…A significant association was present between single-fraction therapy and OPP, and there was a significant difference in OPP-free survival between single- and multi-fraction regimens (p=0.0052, Figure 2). Interestingly, the two recently reported cases of pseudoprogression of soft tissue components of bone lesions have also been in single-fraction regimens 7 . This suggests that the higher biological dose delivered by single-fraction regimens plays a role in development of OPP.…”

“…Tumor growth due to necrosis in response to therapy (chemo- and radiation) is a well-known phenomenon 8 that likely plays a role in the development of OPP. Indeed, a recent case report in a patient with pseudoprogression in the soft tissue (epidural) component of a spine lesion following SSRS showed necrosis in the early (<8 weeks) post-SSRS period 7 . The effect of radiation on the surrounding bone can be extrapolated from experimental data in animals on the effect of conventional radiation therapy over time, and compared with time course of OPP (Figure 3).…”

“…This difference is not unexpected given the differences between the local environments encountered in bone and brain. Temporal evolution information was not obtained in the aforementioned case series on soft tissue pseudoprogression 7 , since both reported lesions were treated following the development of pseudoprogression due to symptoms (steroids in one case, and laminectomy in the other).…”

The Downside of Radiosurgery, Possible Complications

“…Notwithstanding that a variable rate of SRS induced neurological complications (ranging from 2 to 32%) has been reported, only 3 to 5% of patients still presented neurological deficits at the time of the last follow-up117,118,138,141 . It is essential to highlight that the signal changes on MRI associated with clinical deterioration, despite being transitory in many cases, are frequently incorrectly interpreted as RN.…”