Clinical Investigation
Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials

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Purpose

There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival.

Methods and Materials

Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derived survival score.

Results

Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P=.007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P<.001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P<.001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P<.05).

Conclusions

We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.

Introduction

Spine metastasis can pose significant functional consequences because it produces structural compromise and/or neurologic sequela. The main modalities for treatment include surgery, conventionally fractionated radiation, and stereotactic spine radiation surgery (SSRS) (1). SSRS represents one of the newest of these treatment modalities, with reports of high rates of local control, symptom control, and maintenance of neurological function without substantial toxicities 2, 3, 4. To achieve this, SSRS uses advanced target tracking, patient immobilization, and radiation planning to administer relatively large doses of conformal radiation while minimizing normal tissue doses 5, 6.

However, compared to conventionally fractionated radiation, SSRS requires greater planning time, additional personnel involvement, and considerable technical investment. Moreover, SSRS carries additional risk compared to that with conventional radiation, including the potential for vertebral body fracture, myelopathy, or radiculopathy 7, 8. The benefits of SSRS compared to conventional radiation techniques lie in its ability to provide durable control and pain relief for well-selected patients 9, 10, 11. Given the heterogeneity in survival outcomes among patients with metastases, it remains unclear who might derive benefit from SSRS compared to less involved treatments. To address this, various groups have created prognostic models to stratify patients after surgical resection or conventional radiation 12, 13, 14, 15. However, there are limited models that describe survival after SSRS (16).

There is a wide spectrum of patient survival after metastasis. On one end of the spectrum are patients who, despite developing metastatic disease, exhibit slow disease progression and good functional status 17, 18. In these patients with potentially excellent survival, intensifying treatment may be justified. In contrast, there also exists a patient population with poor performance status and advanced metastatic disease. In these patients with poor survival, consideration should be made for therapies less involved than SSRS, including hospice or conventional fractionated radiation. We hypothesized that a survival stratification score could be created to identify the outlying patients with poor and excellent survival. We attempted to do so by analyzing patients enrolled in 2 mature institutional prospective SSRS trials. In addition, because symptom burden has been correlated with survival in previous studies 19, 20, 21, 22, we evaluated the prognostic ability of pretreatment symptoms and their correlation with the presented survival model.

Section snippets

Patient selection

A total of 209 patients were enrolled in 2 phase 1-2 trials between 2002 and 2011, evaluating treatment with single or multifraction SSRS for spinal metastasis at our institution. Indications for treatment were oligometastatic disease, medical inoperability, residual tumor after surgery, failure of previous local therapy, radiation-resistant histology, or surgery refusal. Protocol inclusion criteria included the Karnofsky performance score (KPS) >40, histopathological confirmation of cancer at

Patient demographics

Among 209 patients enrolled in both studies, 3 patients were removed from analysis due to short (<3-year) follow-up. Patient characteristics are presented in Table 1. Fifty-four percent of patients (n=111) were female, and 97% had a KPS of >70 and a median of 1 (range, 0-5) organ system outside of bone involved with metastatic disease. The most common histology treated was renal cell carcinoma (n=77 [37%]), and the most frequent extraosseous organ system involved with metastasis was lung (n=69

Discussion

We present a survival model intended to define poor and excellent risk subgroups, using 7 pretreatment variables: sex, KPS, previous surgery at the SSRS site, previous radiation at the SSRS site, number of organ systems involved with metastases, whether the SSRS site is the only site of disease, and the interval between initial diagnosis and detection of metastasis. We labeled this the prognostic index after spinal metastases (PRISM) model. Significant findings from this analysis include

Conclusions

In conclusion, patients treated with SSRS for metastatic disease may be stratified by a prognostic scoring system into poor and excellent survivors. Following validation of this score in an independent dataset, the presented PRISM model may aid in selecting patients for aggressive treatment options including SSRS versus more conservative options such as hospice. Given that this study was derived from prospective single-institution trials, using patients with good function status (majority of

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    This work was supported in part by Cancer Center Support (Core) grant CA016772 to the University of Texas MD Anderson Cancer Center.

    Conflict of interest: none.

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