Stereotactic Spinal Radiosurgery and Delayed Vertebral Fracture Risk

摘要

The spine is one of the most common sites for tumor metastasis.1Suva L.J. Washam C. Nicholas R.W. Griffin R.J. Bone metastasis: Mechanisms and therapeutic opportunities.Nat Rev Endocrinol. 2011; 7: 208-218Crossref PubMed Scopus (280) Google Scholar It is estimated that approximately 30% of all patients with cancer develop spinal metastasis at some point in their cancer course.2Boyce-Fappiano D. Elibe E. Schultz L. et al.Analysis of the factors contributing to vertebral compression fractures after spine stereotactic radiosurgery.Int J Radiat Oncol Biol Phys. 2017; 97: 236-245Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Spinal metastatic disease can cause significant morbidity in patients, including pain, hypercalcemia, pathologic fractures, spinal instability, and compression of the spinal cord or cauda equina.3Coleman R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity.Clin Cancer Res. 2006; 12: 6243s-6249sCrossref PubMed Scopus (1705) Google Scholar Management of spinal metastases can be complex and may benefit from multimodal therapeutic strategies to achieve optimal outcomes. Stereotactic spinal radiosurgery (SSRS) is an emerging technique that has been developed to deliver highly conformal ionizing radiation doses, designed to control gross disease while simultaneously minimizing dose to surrounding critical structures such as the spinal cord. Current data on SSRS suggest favorable local control rates of approximately 90% at 1 year, complete pain response of approximately 50%, and low rates of high-grade toxicity.4Husain Z.A. Sahgal A. De Salles A. et al.Stereotactic body radiation therapy for de novo spinal metastases: Systematic review.J Neurosurg Spine. 2017; 27: 295-302Crossref PubMed Scopus (97) Google Scholar However, as with all emerging technologies, understanding the potential complications of novel therapies such as SSRS is fundamental to safely implementing this technology throughout the wider oncology community. The focus of this case and review is the risk of vertebral fracture after SSRS. A 54-year old male patient presented with a progressively worsening cough. His medical history was notable for smoking half a pack of cigarettes daily for 35 years but was otherwise unremarkable. Further evaluation included an 18F-fluorodeoxyglucose positron emission/computed tomography (FDG-PET/CT) scan that revealed 2 right upper-lung nodules, 2 enlarged mediastinal lymph nodes, a left adrenal gland lesion, and a lesion involving the left posterolateral elements of the T6 vertebrae (Fig 1A). Endoscopically guided biopsy of a right upper-lung nodule and the left adrenal mass revealed concordant poorly differentiated adenocarcinoma of primary lung origin. After multidisciplinary tumor board discussion, systemic therapy was recommended. The patient was treated with 6 cycles every 21 days of gemcitabine (1250 mg/m2/d on days 1 and 8), cisplatin (80 mg/m2/d on day 1), and bevacizumab (7.5 mg/kg/d on day 1). A reevaluation with FDG-PET/CT scan 4.5 months after the initial diagnosis showed a mixed response with decreased FDG uptake in the right upper-lung nodules and mediastinal lymph nodes, stable FDG uptake in the left adrenal gland, and increased FDG uptake in the left pedicle of T6 (Fig 1B). There was no evidence of new metastatic disease. After further multidisciplinary discussion, continuation of systemic therapy was recommended. The patient was reinitiated on 1 additional cycle of gemcitabine, cisplatin, and bevacizumab (7 total cycles) and then switched to pemetrexed (500 mg/m2/d on day 1), carboplatin (area under the curve 6 on day 1), and bevacizumab (15 mg/kg/d on day 1) for 3 cycles (10 cycles total). Bevacizumab was omitted during the 10th total cycle in preparation for stereotactic radiation therapy. A reevaluation with FDG-PET/CT scan 7.5 months after initial diagnosis showed further response in the right upper-lung nodules, T6 lesion, and left adrenal. There was c