Long Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression treated with Hybrid Therapy (Surgery followed by Stereotactic Body Radiation Therapy)
BACKGROUND:"Hybrid-therapy", consisting of separation-surgery followed by stereotactic body radiation therapy (SBRT) has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study is to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS:This is a retrospective study performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid-therapy for high-grade epidural spinal cord or nerve root compression from 2005-2020 were included. Outcome variables evaluated included patient demographics, overall survival (OS) and progression-free survival (PFS), surgical and radiation complications, and clinical-genomic correlations. RESULTS:Fifty patients met inclusion criteria. Progression of disease occurred in 7 (14%) patients at the index-level requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. Adenomatous polyposis coli (APC) exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at another spinal levels. CONCLUSIONS:Hybrid-therapy in CRC patients resulted in 86.7% local control at two years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.
The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy)
BACKGROUND:In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE:To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS:This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS:One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION/CONCLUSIONS:Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.
Patient outcomes following implementation of an enhanced recovery after surgery pathway for patients with metastatic spine tumors
BACKGROUND:Metastatic spine tumor surgery consists of palliative operations performed on frail patients with multiple medical comorbidities. Enhanced recovery after surgery (ERAS) programs involve an evidence-based, multidisciplinary approach to improve perioperative outcomes. This study presents clinical outcomes of a metastatic spine tumor ERAS pathway implemented at a tertiary cancer center. METHODS:The metastatic spine tumor ERAS program launched in April 2019, and data from January 2018 to May 2020 were reviewed. Measured outcomes included the following: hospital length of stay (LOS), time to ambulation, urinary catheter duration, time to resumption of diet, intraoperative fluid intake, estimated blood loss (EBL), and intraoperative and postoperative day 0-5 cumulative opioid use (morphine milligram equivalent [MME]). RESULTS:A total of 390 patients were included in the final analysis: 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program and 213 consecutive pre-ERAS patients. Although the mean case durations were similar in the ERAS and pre-ERAS cohorts (265 vs. 274Â min; p = .22), the ERAS cohort had decreased EBL (157 vs. 215Â ml; p = .003), decreased postoperative day 0-5 cumulative mean opioid use (178 vs. 396 MME; pÂ <Â .0001), earlier ambulation (mean, 34 vs. 57Â h; p = .0001), earlier discontinuation of urinary catheters (mean, 36 vs. 56Â h; pÂ <Â .001), and shorter LOS (5.4 vs. 7.5Â days; pÂ <Â .0001). CONCLUSIONS:The implementation of a multidisciplinary ERAS program designed for metastatic spine tumor surgery led to improved clinical quality metrics, including shorter hospitalizations and significant reductions in opioid consumption.
Development and external validation of predictive algorithms for 6-week mortality in spinal metastasis using 4304 Patients from 5 Institutions
BACKGROUND CONTEXT/BACKGROUND:Historically, spine surgeons used expected postoperative survival of 3-months to help select candidates for operative intervention in spinal metastasis. However, this cutoff has been challenged by the development of minimally invasive techniques, novel biologics, and advanced radiotherapy. Recent studies have suggested that life expectancy of 6 weeks may be enough to achieve significant improvements in postoperative health-related quality of life. PURPOSE/OBJECTIVE:The purpose of this study was to develop a model capable of predicting 6-week mortality in patients with spinal metastases treated with radiation or surgery. STUDY DESIGN/SETTING/METHODS:Retrospective review was conducted at five large tertiary centers in the United States and Taiwan. PATIENT SAMPLE/METHODS:The development cohort consisted of 3,001 patients undergoing radiotherapy and/or surgery for spinal metastases from one institution. The validation institutional cohort consisted of 1,303 patients from four independent, external institutions. OUTCOME MEASURES/METHODS:The primary outcome was six-week mortality METHODS: Five models were considered to predict six-week mortality, and the model with the best performance across discrimination, calibration, decision-curve analysis, and overall performance was integrated into an open access web-based application. RESULTS:The most important variables for prediction of 6-week mortality were albumin, primary tumor histology, absolute lymphocyte, three or more spine metastasis, and ECOG score. The elastic-net penalized logistic model was chosen as the best performing model with AUC 0.84 on evaluation in the independent testing set. On external validation in the 1,303 patients from the four independent institutions, the model retained good discriminative ability with an area under the curve of 0.81. The model is available here: https://sorg-apps.shinyapps.io/spinemetssurvival/. CONCLUSIONS:While this study does not advocate for the use of 6-week life expectancy as a criteria for considering operative management, the algorithm developed and externally validated in this study may be helpful for preoperative planning, multidisciplinary management, and shared decision making in spinal metastasis patients with shorter life expectancy.
Responder Analysis of Pain Relief After Surgery for the Treatment of Spinal Metastatic Tumors
BACKGROUND:Central tendency analysis studies demonstrate that surgery provides pain relief in spinal metastatic tumors. However, they preclude patient-specific probability of treatment outcome. OBJECTIVE:To use responder analysis to study the variability of pain improvement. METHODS:In this single-center, retrospective analysis, 174 patients were studied. Logistic regression modeling was used to associate preoperative characteristics with rating the Brief Pain Inventory (BPI) worst pain item 0 to 4. Linear regression modeling was used to associate preoperative characteristics with minimal clinically important improvement (MCI) in physical functioning defined by a 1-point decrease in the BPI Interference Construct score from preoperative baseline to 6 months postoperatively. RESULTS:Patient-level analysis revealed that 60% of patients experienced an improvement in pain. At least half experienced a decrease in pain resulting in MCI in physical functioning. Cutpoint analysis revealed that 48% were responders. Increasing scores on the preoperative pain intensity BPI items, the MD Anderson Symptom Inventory (MDASI) Core Symptom Severity Construct, the MDASI Spine Tumor-Specific Construct, the presence of preoperative neurologic deficits, and postoperative complications were associated with lower probability of treatment success while increasing severity in all BPI pain items, and MDASI constructs were associated with increased probability of MCI in physical function. Significant mortality and loss to follow-up intrinsic to this patient population limit the strength of these data. CONCLUSION/CONCLUSIONS:Although patients with milder preoperative symptoms are likely to achieve better pain relief after surgery, patients with worse preoperative symptom also benefit from surgery with adequate pain relief with an improvement in physical function.
Clinical Reliability of Genomic Data Obtained from Spinal Metastatic Tumor Samples
PURPOSE/OBJECTIVE:The role of tumor genomic profiling is rapidly growing as it results in targeted, personalized, cancer therapy. Though routinely used in clinical practice, there are no data exploring the reliability of genomic data obtained from spine metastases samples often leading to multiple biopsies in clinical practice. This study compares the genomic tumor landscape between spinal metastases and the corresponding primary tumors as well as between spinal metastases and visceral metastases. PATIENTS AND METHODS/METHODS:Spine tumor samples, obtained for routine clinical care from 2013 to 2019, were analyzed using MSK-IMPACT, a next generation sequencing assay. These samples were matched to primary or metastatic tumors from the corresponding patients. A concordance rate for genomic alterations was calculated for matching sample pairs within patients for the primary and spinal metastatic tumor samples as well as for the matching sample pairs within patients for the spinal and visceral metastases. For a more robust and clinically relevant estimate of concordance, a subgroup analyses of previously established driver mutations specific to the main primary tumor histologies was performed. RESULTS:Eighty-four patients contributed next generation sequencing from a spinal metastasis and at least one other site of disease: 54 from the primary tumor, 39 had genomic tumor data from another, non-spinal metastasis, 12 patients participated in both subsets. For the cohort of matched primary tumors and spinal metastases (n = 54) comprised of mixed histologies, we found an average concordance rate of 96.97% for all genetic events, 97.17% for mutations, 100% for fusions, 89.81% for deletions, and 97.01% for amplifications across all matched samples. Notably, >25% of patients harbored at least one genetic variant between samples tested, though not specifically for known driver mutations. The average concordance rate of driver mutations was 96.99% for prostate cancer, 95.69% (p = 0.0004513) for lung cancer and 96.43% for breast cancer. An average concordance of 99.02% was calculated for all genetic events between spine metastases and non-spinal metastases (n=41) and, more specifically, a concordance rate of 98.91% was calculated between spine metastases and liver metastases (n=12) which was the largest represented group of non-spine metastases. CONCLUSION/CONCLUSIONS:Sequencing data performed on spine tumor samples demonstrate a high concordance rate for genetic alterations between the primary tumor and spinal metastasis as well as between spinal metastases and other, visceral metastases, particularly for driver mutations. Spine tumor samples may be reliably used for genomic based decision making in cancer care, particularly for prostate, NSCLC and breast cancer.
Systemic considerations for the surgical treatment of spinal metastatic disease: a scoping literature review
Systemic assessment is a pillar in the neurological, oncological, mechanical, and systemic (NOMS) decision-making framework for the treatment of patients with spinal metastatic disease. Despite this importance, emerging evidence relating systemic considerations to clinical outcomes following surgery for spinal metastatic disease has not been comprehensively summarised. We aimed to conduct a scoping literature review of this broad topic. We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL databases from Jan 1, 2000, to July 31, 2021. 61 articles were included, accounting for a total of 22â€ˆ335 patients. Preoperative systemic variables negatively associated with postoperative clinical outcomes included demographics (eg, older age [>60 years], Black race, male sex, low or elevated body-mass index, and smoking status), medical comorbidities (eg, cardiac, pulmonary, hepatic, renal, endocrine, vascular, and rheumatological), biochemical abnormalities (eg, hypoalbuminaemia, atypical blood cell counts, and elevated C-reactive protein concentration), low muscle mass, generalised motor weakness (American Spinal Cord Injury Association Impairment Scale grade and Frankel grade) and poor ambulation, reduced performance status, and systemic disease burden. This is the first comprehensive scoping review to broadly summarise emerging evidence relevant to the systemic assessment component of the widely used NOMS framework for spinal metastatic disease decision making. Medical, surgical, and radiation oncologists can consider these findings when prognosticating spinal metastatic disease-related surgical outcomes on the basis of patients' systemic condition. These factors might inform a shared decision-making approach with patients and their families.
Influence of Healthcare Disparities on Outcomes for Spinal Metastasis Patients [Meeting Abstract]
Introduction: The objective of this analysis was to compare sociodemographic characteristics and outcomes between cohorts of patients receiving separation surgery for spinal metastases at two neighboring institutions, one private and one public, affiliated with a major academic medical center in a large metropolitan area.
Method(s): Patients who received separation surgery for spinal metastases between 2013 and 2021 were included in this analysis. Sociodemographic factors, treatment characteristics, and outcomes were compared between those treated at a private hospital and those treated at a neighboring public hospital using Rao-Scott chi square tests.
Result(s): Compared to those treated at our private hospital, patients treated at our public hospital were more often younger (p=0.005), of Black or Hispanic race (70% vs. 14.9%, p<0.001), and insured via Medicaid or Emergency Medicaid (48.6% vs. 3.2%, p<0.001). They more frequently presented with ESCC grade 3 compression (81.6% vs. 49.2%), potentially unstable or unstable lesions as denoted by SINS >7 (64.1% vs. 37.7%), and increased neurologic impairment as denoted by ASIA Impairment Scale scores of A, B, or C (35% vs. 7.9%). Local progression was less frequently observed in patients treated at our public hospital (28.2% vs. 54.7%, p=0.001), although this is likely due to poorer clinical and radiographic follow-up amongst this cohort. Median survival was significantly lower in patients treated at our public hospital (Median [Range]: 81 [11-1,873] days vs. 264 [0-3,092] days, p<0.001), although this is also likely confounded by lower rates of follow-up.
Conclusion(s): This study highlights substantial disparities amongst patients treated for spinal metastases at neighboring institutions affiliated with a major academic medical center. Further work is needed to identify reasons for these disparities and create avenues by which to mitigate them
Calculating Utilities From the Spine Oncology Study Group Outcomes Questionnaire: A Necessity for Economic and Decision Analysis
STUDY DESIGN/METHODS:General population utility valuation study. OBJECTIVE:The aim of this study was to develop a technique for calculating utilities from the Spine Oncology Study Group Outcomes Questionnaire v2.0 (SOSGOQ2.0). SUMMARY OF BACKGROUND DATA/BACKGROUND:The ability to calculate quality-adjusted life-years (QALYs) for metastatic spine disease would enhance treatment decision-making and facilitate economic analysis. QALYs are calculated using utilities. METHODS:Using a hybrid concept-retention and factorial analysis shortening approach, we first shortened the SOSGOQ2.0 to eight items (SOSGOQ-8D). This was done to lessen the cognitive burden of the utility valuation exercise. A general population sample of 2730 adults was then asked to evaluate 12 choice sets based on SOSGOQ-8D health states in a Discrete Choice Experiment. A utility scoring rubric was then developed using a mixed multinomial-logit regression model. RESULTS:We were able to reduce the SOSGOQ2.0 to an SOSGOQ-8D with a mean error of 0.003 and mean absolute error of 3.078 compared to the full questionnaire. The regression model demonstrated good predictive performance and was used to develop a utility scoring rubric. Regression results revealed that participants did not regard all SOSGOQ-8D items as equally important. CONCLUSION/CONCLUSIONS:We provide a simple technique for converting the SOSGOQ2.0 to utilities. The ability to evaluate QALYs in metastatic spine disease will facilitate economic analysis and patient counseling. We also quantify the importance of individual SOSGOQ-8D items. Clinicians should heed these findings and offer treatments that maximize function in the most important items.Level of Evidence: 3.
Spnal metastases 2021: a review of the current state of the art and future directions
Spinal metastases are an increasing societal health burden secondary to improvements in systemic therapy. Estimates indicate that 100,000 or more people have symptomatic spine metastases requiring management. While open surgery and external beam radiotherapy have been the pillars of treatment, there is growing interest in more minimally invasive technologies (eg separation surgery) and non-operative interventions (eg percutaneous cementoplasty, stereotactic radiosurgery). The great expansion of these alternatives to open surgery and the prevalence of adjuvant therapeutic options means that treatment decision making is now complex and reliant upon multidisciplinary collaboration. To help facilitate construction of care plans that meet patient goals and expectations, clinical decision aids and prognostic scores have been developed. These have been shown to have superior predictive value relative to more classic prediction models and may become an increasingly important aspect of the clinical practice of spinal oncology. Here we overview current therapeutic advances in the management of spine metastases and highlight emerging areas for research. Given the rapid advancements in surgical technologies and adjuvants, the field is likely to undergo further transformative changes in the coming decade.