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.
Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an “adhesion synapse,” a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor κB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies.
In the largest series to date comparing operative and non-operative management of adult spinal deformity in elderly patients greater than 75 years of age, reconstructive surgery provides significant improvements in pain and disability over a 2-year period. Furthermore, operative patients were more likely to reach MCID than non-operative patients. When counseling elderly patients with ASD, such data may be helpful in the decision-making process regarding treatment.
Introduction Surgical treatment and cement augmentation procedures are effective palliative techniques for the treatment of symptomatic spinal metastases. However, clinical results specific to a breast cancer cohort are generally lacking. We aim to systematically review the literature for clinical outcomes following operative interventions and prognostic factors for the treatment of breast metastases to the spine. Specifically, we describe the survival and clinical outcomes of surgery and cement augmentation procedures for breast metastases to the spine and to determine prognostic variables that may help recognize which patients will perform better or worse following surgery. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results A total of 19 surgical studies, 4 cement augmentation studies, and 6 nonsurgical prognostic variable studies met the preset inclusion criteria. All but three studies (two surgical and one cement augmentation) were retrospective in nature, and all studies were of level of evidence IV. Median postoperative survival for metastatic breast cancer was 21.7 months (8.2–36 months), mean rate of pain improvement was 92.9% (76–100%), mean rate of neurological improvement was 63.8% (53–100%), mean rate neurological decline was 4.1% (0–8%), and mean rate LTC was 92.6% (89–100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included: hormonal (estrogen and progesterone) and HER2 receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, studies consistently found that surgery resulted in neurological improvement for a majority of patients, with a minimal risk of worsening, and kyphoplasty studies reported a high rate of pain control. Increased postoperative survival 2002 onwards was likely due to FDA approval of new chemotherapies. However, specific factors associated with shorter survival following surgery involve hormone and HER2 receptor status and disease-free interval.
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