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

Abstract

Background and Purpose Osseous pseudoprogression (OPP) on MRI can mimic true progression in lesions treated with spine stereotactic radiosurgery (SSRS). Our aim is to describe the prevalence and time course of OPP, in order to assist radiologists in assessment of post-SSRS patients. Materials and Methods A secondary analysis of two prospective trials was performed. MRIs before and after SSRS were assessed for response. OPP was defined as transient growth in signal abnormality centered at the lesion with a sustained decline on follow-up MRI that was not attributable to chemotherapy. Results From the initial set of 223 patients, 37 lesions in 36 patients met inclusion criteria and were selected for secondary analysis. Five of the 37 lesions (14%) demonstrated OPP and 9 demonstrated progressive disease. There was significant association between single-fraction therapy and the development of OPP (p=0.01), and there was a significant difference in OPP-free survival between single- and multi-fraction regimens (p=0.0052). In lesions demonstrating OPP, time to peak size occurred between 9.7 and 24.4 weeks after SSRS (mean: 13.9 weeks, 95% CI: 8.6–19.1 weeks). The peak lesion size was between 4–10 mm larger than baseline. Most lesions returned to baseline size between 23–52.4 weeks following SSRS. Conclusions Progression on MRI obtained between 3 and 6 months following SSRS should be treated with caution, as OPP may be seen in > 1/3 of these lesions. Single-fraction SSRS may be associated with OPP. The possibility of OPP should be incorporated into prospective criteria for assessment of local control following SSRS.

Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: Current challenges and future directions

“…Symptoms or vertebral fractures at the time of tumour growth on imaging did not occur in any of the patients who were deemed to have PP. These findings are similar to the series by Amini et al, which demonstrated a PP rate of 14% and median time to occurrence of 5 months 26 . It is worth noting that the use of the 80% isodose line to describe the high dose region was extrapolated from the CNS setting and has not been validated for the spine.…”

“…However, for patients with spine metastases, unless there is cord compromise or vertebral instability, a conservative approach with serial imaging is usually adopted given the invasive nature and morbidity of surgery which may ultimately prove to be unnecessary. Earlier reports describing PP following spine SABR 26‐29 have recently been followed by two more recent publications. Bahig et al performed a retrospective quantitative analysis of 49 spinal lesions treated with SBRT 30 .…”

“…It is possible that we might observe an increase in PP rates in patients treated with both immunotherapy and SBRT. Osseous PP following SBRT is an early feature on imaging studies with time to peak size occurring between 9.7 and 24.4 weeks in one series 26 . It is important to accurately differentiate between PP and true local recurrence (LR), as the latter has significant implications for the patient in terms of further intervention with, for example, biopsy, surgery, re‐irradiation and change in systemic treatment.…”

Reirradiation spine stereotactic body radiation therapy for spinal metastases: systematic review

“…Furthermore, an experienced neuroradiologist is imperative to assess whether changes seen on imaging are related to disease progression versus radiation-induced change, because osseous pseudoprogression has been reported and is an active area of investigation. 2 Similarly, for pain control, the lack of standardization in the pain assessment tool and time points at which response was determined are confounding factors. The SPIne response assessment in Neuro-Oncology (SPINO) group was formed to address such issues.…”

Stereotactic Body Radiotherapy for Spinal Metastases

“…The association of single-fraction SBRT (versus multifraction) with greater pain flare rates, 13 and emerging evidence of early-onset pseudoprogression 14 are clinical surrogates confirming an early intense inflammatory reaction. Alternatively, we postulate that late-onset VCF is because of the slow induction of necrosis yielding damage to the vertebral body boney and cartilaginous structure that eventually compromises the capacity of the vertebral body to withstand the mechanical load, manifesting as VCF.…”