br Surgery is the standard of care for patients
Surgery is the standard of care for patients with pathologic ver-tebral o-Phenanthroline fractures secondary to degeneration from metastatic disease, regardless of primary cancer type. Vertebral augmentation is first-line when the fracture is stable, or if unstable and the patient is not a surgical candidate. Adjuvant chemotherapy and radiation should be determined on an individual basis . Cord compression is a known negative prognostic factor, often resulting in increased levels of pain and neurologic deficits. Ten to twenty percent of patients with spinal metastases experience MESCC from posterior extension of the tumor from the vertebral body into the epidural space. This most commonly occurs in the thoracic spine, comprising approximately sixty to eighty percent of cases. The standard of care for these cases is a combination of surgery and radiation. Surgeries that show success in managing
MESCC include spinal cord decompression and tumor resection. Concomitant corticosteroids are administered along with surgery in order to prevent further development of neurologic deficits. Those cases of MESCC in which radiation therapy, specifically cEBRT, is expected to improve survival include patients with suffi-ciently long life expectancy, which could lend to the increased sur-vival in the non-operative group. Conversely, as the majority of these patients are not surgical candidates, their involvement in operations may have contributed to the decreased life expectancy of the operative cohort.
Various prognostic factors of metastatic spine disease have been identified to predict postoperative outcomes and survival. Favorable characteristics include: ECOG scale of performance sta-tus, higher Karnofsky performance status (KPS) score, female gen-der, primary histological diagnosis of adenocarcinoma, absence of appendicular metastases, lack of pathologic fracture, use of adju-vant chemotherapy and radiation, preoperative ambulation, and slower preoperative primary tumor growth rate. Unfavorable char-acteristics include: pathologic fracture in extraspinal metastases, complete pathologic fracture, primary histological diagnosis of SCLC, absence of adjuvant chemotherapy and radiation, visceral metastases, and greater number of spinal segments affected.
Furthermore, the mutational status of lung cancer holds utility as a prognostic factor. Various receptors, such as the epithelial growth factor receptor (EGFR) and estrogen receptor have a role in carcinogenesis and metastatic potential. These mutations can be treated with director inhibitors, decreasing cancer proliferation and leading to better survival. Mutational status can thus be a useful indicator for more aggressive, operative treatments.
5. Limitations of the study
This study is a systematic review of current literature and therefore can only demonstrate associations rather than causality.
The majority of included studies were case reports and retrospec-tive case series/reports, which often carry less clinical value than a randomized controlled trial and other research projects. As our findings represent an aggregate of these studies, concerns of exter-nal validity and reliability must be considered in the interpretation of our conclusions.
As treatment modality is based on patient characteristics and presenting disease burden, patients with increased disease burden were likely to undergo more aggressive treatment than patients with better prognosis. Thus outcomes may be skewed based on patient presentation. For example, those that underwent an oper-ation likely did so because of MESCC, which is a known negative prognostic factor. Additionally, the majority of included literature did not document mutational status and thus was not included in our survival analyses.
6. Future directions
Randomized clinical trials for different groups of patients with metastatic spinal disease should be performed in order to more accurately analyze treatment modalities on the basis of presenta-tion (asymptomatic, uncomplicated, MESCC, stable or unstable fracture) and evaluate outcomes in regards to symptomatic relief, recurrence, morbidity, mortality, and change in life expectancy. For each treatment algorithm, an analysis of risk factors should be performed to further extricate potential confounders. The effects of novel therapies currently in clinical trials, including bio-logic chemotherapy and radiotherapy techniques, should be included as well. As this study details a unique population with a very aggressive type of cancer, further studies should analyze the efficacy and outcomes of more aggressive treatments of spinal metastases of various primary cancers.