Summary The abscopal effect is a phenomenon in which local radiotherapy is associated with the regression of metastatic cancer at a distance from the irradiated site. The abscopal effect may be mediated by activation of the immune system. Ipilimumab is a monoclonal antibody that inhibits an immunologic checkpoint on T cells, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). We report a case of the abscopal effect in a patient with melanoma treated with ipilimumab and radiotherapy. Temporal associations were noted: tumor shrinkage with antibody responses to the cancer–testis antigen NY-ESO-1, changes in peripheral-blood immune cells, and increases in antibody responses to other antigens after radiotherapy. (Funded by the National Institutes of Health and others.)

Background. Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan-Kettering Cancer Center to determine the optimal therapy for patients with spine metastases. Methods. We provide a literature review of the integral publications that serve as the basis for the NOMS framework and report the results of systematic implementation of the NOMSguided treatment. Results. The NOMS decision framework consists of the neurologic, oncologic, mechanical, and systemic considerations and incorporates the use of conventional external beam radiation, spinal stereotactic radiosurgery, and minimally invasive and open surgical interventions. Review of radiation oncology and surgical literature that examine the outcomes of treatment of spinal metastatic tumors provides support for the NOMS decision framework. Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population. Conclusion. NOMS paradigm provides a decision framework that incorporates sentinel decision points in the treatment of spinal metastases. Consideration of the tumor sensitivity to radiation in conjunction with the extent of epidural extension allows determination of the optimal radiation treatment and the need for surgical decompression. Mechanical stability of the spine and the systemic disease considerations further help determine the need and the feasibility of surgical intervention. The Oncologist 2013;18:744 -751 Implications for Practice: Treatment of spinal metastatic tumors requires a multidisciplinary approach which integrates radiation and medical oncology, surgery, and interventional radiology. The NOMS framework described in this manuscript incorporates the neurologic, oncologic, mechanical, and systemic considerations to facilitate decision making in the care of patients with spinal metastases. Furthermore, this framework allows dynamic integration of novel systemic and radiation options which is crucial in these rapidly evolving disciplines. The article summarizes the supporting literature for this framework and provides the results of implementation of the NOMS paradigm in the care of cancer patients. INTRODUCTIONSpinal metastases occur in 20% of all patients with cancer [1, 2], with 5%-10% of patients with cancer developing spinal cord compression [3,4]. The treatment of spinal metastases is palliative, with the goals of providing pain relief, maintenance or recovery of neurologic function, local durable tumor control, spinal stability, and improved quality of life. Over the past decade, treatment has evolved from simple decisions regarding the need for either surgery or conventional external beam...

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OBJECT Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurologic function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression. The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy (IG-IMRT) delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control. METHODS A retrospective chart review identified 186 patients with epidural spinal cord compression from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (22%), high-dose hypofractionated SRS (24-30 Gy in 3 fractions) in 37 patients (20%), or low-dose hypofractionated SRS (18-36 Gy in 5 or 6 fractions) in 109 patients (58%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology-specific radiosensitivity, grade of epidural spinal cord compression, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis. RESULTS The total cumulative incidence of local progression was 16.4% one year after SRS. Multivariate Gray’s competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year; hazard ratio = 0.12, p = 0.04) as compared to low-dose hypofractionated SRS (22.6% local progression at 1 year; HR = 1). Although univariate analysis demonstrated a trend towards greater risk of local progression for patients that failed preoperative cEBRT (22.2% local progression at 1 year, HR = 1.96, p = 0.07) compared to patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR = 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of epidural spinal cord compression, extent of surgical decompression, or gender. CONCLUSIONS Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology-specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated one-year local progression rates less than 5% (95% CI: 0-12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after single-fraction SRS was less than 10% (95% CI: 0-19.0%).

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The ESCC scale provides a valid and reliable instrument that may be used to describe the degree of ESCC based on T2-weighted MR images. This scale accounts for recent advances in the treatment of spinal metastases and may be used to provide an ESCC classification scheme for multicenter clinical trial and outcome studies.

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Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigate the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single fraction SRS for BMs. A total of 113 BMs (91% intact, 9% post-operative) were treated with median dose 21Gy (15-24Gy). Ipi was given at 3mg/kg (54%) or 10mg/kg (46%) for a median of 4 doses (1-21). Adverse events were recorded using CTCAE 3.0. Kaplan-Meier methods were used to estimate survival and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with timing of SRS/Ipi (p=0.035) and melanoma-specific graded prognostic assessment (p=0.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence (RR) than those treated with SRS after Ipi (1-yr OS 65% vs. 56% vs. 40%, p=0.008; 1-yr RR 69% vs. 64% vs. 92%, p=0.003). SRS during Ipi also yielded a trend toward less local recurrence (LR) than SRS before or after Ipi (1-yr LR 0% vs. 13% vs. 11%, p=0.21). On MRI, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but only 13% of patients treated after Ipi. Grade 3-4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly due to enhanced immunomodulatory effect.