Surgical oncology is a diverse field in medicine and has undergone a significant paradigm shift over the past few decades. This shift in both medical and surgical management of patients with primarily metastatic tumors has largely been due to the more complete understanding of tumor biology as well as due to advances in surgical approaches and instrumentation. Furthermore, radiation oncology has seen significant advances with stereotactic radiosurgery and intensity-modulated radiation therapy contributing to a decline in surgical treatment of metastatic spinal disease. We analyze the entire spectrum of treating patients with metastatic spinal disease, from methods of diagnosis to the variety of treatment options available in the published literature.
A review of recent literatures providing complication rates for ASD surgery was performed, providing the most up-to-date incidence of early and late complications. Providers may use such data in helping to counsel patients of the literature-supported complication rates of such procedures despite the planned benefits, thus obtaining a more thorough informed consent.
Extracorporeal photochemotherapy (ECP) is employed for the management of cutaneous T cell lymphoma (CTCL). ECP involves the extracorporeal exposure of white blood cells (WBCs) to a photosensitizer, 8-methoxypsoralen (8-MOP), in the context of ultraviolet A (UVA) radiation, followed by WBC reinfusion. Historically, the therapeutic activity of ECP has been attributed to selective cytotoxicity on circulating CTCL cells. However, only a fraction of WBCs is exposed to ECP, and 8-MOP is inactive in the absence of UVA light, implying that other mechanisms underlie the anticancer effects of ECP. Recently, ECP has been shown to enable the physiological differentiation of monocytes into dendritic cells (DCs) that efficiently cross-present tumor-associated antigens (TAAs) to CD8 + T lymphocytes to initiate cognate immunity. However, the source of TAAs and immunostimulatory signals for such DCs remains to be elucidated. Here, we demonstrate that 8-MOP plus UVA light reduces melanoma cell viability along with the emission of ICD-associated danger signals including calreticulin (CALR) exposure on the cell surface and secretion of ATP, high mobility group box 1 (HMGB1) and type I interferon (IFN). Consistently, melanoma cells succumbing to 8-MOP plus UVA irradiation are efficiently engulfed by monocytes, ultimately leading to cross-priming of CD8 + T cells against cancer. Moreover, malignant cells killed by 8-MOP plus UVA irradiation in vitro vaccinate syngeneic immunocompetent mice against living cancer cells of the same type, and such a protection is lost when cancer cells are depleted of calreticulin or HMGB1, as well as in the presence of an ATP-degrading enzyme or antibodies blocking type I IFN receptors. ECP induces bona fide ICD, hence simultaneously providing monocytes with abundant amounts of TAAs and immunostimulatory signals that are sufficient to initiate cognate anticancer immunity.
In 2007, members of our group reported a 21 month median survival for patients undergoing surgery for metastatic breast cancer in the spinal column. Cervical spine metastases were associated with decreased survival, Estrogen receptor positivity was associated with improved survival, and age and visceral metastases did not significantly impact survival. In the current study, we reassess these variables in the context of modern adjuvant therapies, and investigate the impact of the Spinal Instability Neoplastic Score (SINS). We report an observational cohort of 43 patients undergoing surgical resection for metastatic breast cancer of the spine treated at a single academic institution from June 2002 to August 2011. Patient medical records were reviewed in accordance with policies outlined by the University Institutional Review Board. Median overall survival following surgery for metastatic breast cancer in the spine was 26.8 months. 1 year overall survival was 66%. 5 year-overall survival was 4%. Age (p=0.12), preoperative functional status (p=0.17), location of metastasis (p=0.34), the presence of visceral metastases (p=0.68), and spinal instability (p=0.81) were not significant variables on survival analysis. Postoperative adjuvant therapy with a single modality (radiation or chemotherapy) was associated with a significantly lower median survival compared to dual therapy with chemotherapy and radiation (p=0.042). Patients that received radiation and chemotherapy after surgery were younger but demonstrated prolonged median survival versus single modality therapy. This data supports the concept that visceral metastases do not impact survival, however cervical spine lesions were not associated with decreased survival.
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