Quantified CIN Score From Cell-free DNA as a Novel Noninvasive Predictor of Survival in Patients With Spinal Metastasis

Purpose: Most currently available scores for survival prediction of patients with bone metastasis lack accuracy. In this study, we present a novel quantified CIN (Chromosome Instability) score modeled from cfDNA copy number variation (CNV) for survival prediction.Experimental Design: Plasma samples collected from 67 patients with bone metastases from 11 different cancer types between November 2015 and May 2016 were sent through low-coverage whole genome sequencing followed by CIN computation to make a correlation analysis between the CIN score and survival prognosis. The results were validated in an independent cohort of 213 patients.Results: During the median follow-up period of 598 (95% CI 364–832) days until December 25, 2018, 124 (44.3%) of the total 280 patients died. Analysis of the discovery dataset showed that CIN score = 12 was the optimal CIN cutoff. Validation dataset showed that CIN was elevated (score ≥12) in 87 (40.8%) patients, including 5 (5.75%) with head and neck cancer, 11 (12.6%) with liver and gallbladder cancer, 11 (12.6%) with cancer from unidentified sites, 21 (24.1%) with lung cancer, 7 (8.05%) with breast cancer, 4 (4.60%) with thyroid cancer, 6 (6.90%) with colorectal cancer, 4 (4.60%) with kidney cancer, 2 (2.30%) with prostate cancer, and 16 (18.4%) with other types of cancer. Further analysis showed that patients with elevated CIN were associated with worse survival (p < 0.001). For patients with low Tokuhashi score (≤8) who had predictive survival of less than 6 months, the CIN score was able to distinguish patients with a median overall survival (OS) of 443 days (95% CI 301–585) from those with a median OS of 258 days (95% CI 184–332).Conclusion: CNV examination in bone metastatic cancer from cfDNA is superior to the traditional predictive model in that it provides a noninvasive and objective method of monitoring the survival of patients with spine metastasis.

Pre-Operative Modified Glasgow Prognostic Score 2 For The Prediction of Poor Post-Operative Performance Status Following Palliative Surgery For Pathological Spinal Fracture: A Retrospective Cohort Study

Background: Skeletal-related events due to spinal metastasis in cancer significantly impair patients’ activities of daily living and quality of life. Most of these events occur suddenly. To reduce their impairment occurred suddenly, and to allow them to return to their normal life immediately, many patients undergo palliative surgery; however, some patients do not improve their performance status (PS) as expected. There is little evidence regarding the factors influencing a patient’s PS after palliative surgery. We aimed to investigate the pre-operative predictors of poor PS 1 month after surgery.Methods: The study included a consecutive series of 71 patients with pathological spinal fracture who underwent palliative surgery. Pre-operative predictors of poor post-operative PS were investigated. The participants were categorized into two groups according to PS; the Good group (PS 0, 1, or 2) and the Poor group (PS 3 or 4). We performed univariate and multivariable logistic regression analyses on demographic information, unidentified primary site, AIS grade, poor PS, spinal instability neoplastic score, revised Tokuhashi score, New Katagiri score, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio(NLR), and prognostic nutrition index (PNI). Results: Post-operatively, the Poor group included 38.0% of the patients. Univariate analysis revealed that the following pre-operative factors were related to poor outcomes (p<0.05): BMI<18.5; AIS grade C; poor PS; revised Tokuhashi score 0−8; New Katagiri score 7−10; mGPS 2; and PNI. In the multivariate analysis, mGPS 2 (OR = 22.8, 95% CI = 2.59−202.00, p<0.01) was a significant pre-operative predictor of poor post-operative PS. Conclusion: mGPS 2 was a predictive clinical factor that influenced PS 1 month after surgery. Patients with mGPS 2 should be carefully evaluated to determine their treatment, especially whether they should undergo palliative surgery.

Are spine metastasis survival scoring systems outdated and do they underestimate life expectancy? Caution in surgical recommendation guidance

OBJECTIVE Survival scoring systems for spine metastasis (SPM) were designed to help surgical practice. The authors sought to validate the prognostic accuracy of the main preoperative scoring systems for SPM. METHODS It was hypothesized that true patient survival in SPM was better than that predicted using prognosis scores. To investigate this hypothesis, the authors designed a French national retrospective study of a prospectively collected multicenter database involving 739 patients treated for SPM between 2014 and 2017. RESULTS In this series, the median survival time for all patients from an SPM diagnosis was 17.03 ± 1.5 months. Sensitivity and specificity were estimated using the area under the curve (AUC). The AUC of Tomita’s prognosis score was the lowest and poorest (0.4 ± 0.023, range 0.35–0.44), whereas the AUC of the Tokuhashi score was the highest (0.825). The Lei score presented an AUC of 0.686 ± 0.022 (range 0.64–0.7), and the Rades score showed a weaker AUC (0.583 ± 0.020, range 0.54–0.63). Differences among AUCs were all statistically significant (p < 0.001). The modified Bauer score and the Rades score had the highest rate of agreement in predicting survival, with a weighted Cohen’s kappa of 0.54 and 0.41, respectively, indicating a moderate agreement. The revised Tokuhashi and Lei scores had a fair rate of agreement (weighted Cohen’s kappa = 0.24 and 0.22, respectively). The van der Linden and Tomita scores demonstrated the worst performance, with only a “slight” rate of agreement (weighted Cohen’s kappa = 0.19 and 0.16, respectively) between what was predicted and the actual survival. CONCLUSIONS The use of prognostic scoring systems in the estimation of survival in patients with SPM has become obsolete and therefore underestimates survival. Surgical treatment decisions should no longer be based on survival estimations alone but must also take into account patient symptoms, spinal instability, and quality of life.

Minimally-invasive Tubular Surgery Versus Conventional Surgery in the Treatment of Spinal Metastasis: a Retrospective Case-control Study

Background: This study aims to evaluate the perioperative safety and efficacy of minimally-invasive tubular surgery for spinal metastasis with different blood supply.Methods: 72 patients with spinal metastasis between January 2011 to June 2020 were retrospectively reviewed. 14 patients underwent minimally-invasive tubular surgery (Mini-invasive group), and 58 patients underwent conventional surgery (Conventional group). T-test and Mann–Whitney U test was used to evaluate the difference in demographic and perioperative data between the two groups.Results: Baseline characteristics did not differ significantly between the two groups except for the Tokuhashi score (p=0.036). Overall, conventional group had significantly more blood loss (P=0.001), blood transfused(P=0.027), drainage(P<0.001), and longer time of drainage tube(P<0.001), postoperative hospitalization(P=0.002) compared with the mini-invasive group. Sub-analysis showed that for patients with hypo-vascular tumor, trans-channel decompression surgery had all advantages mentioned above. For patients with hyper-vascular tumor, trans-channel decompression surgery only had advantages on the drainage related events. Patients with hyper-vascular tumor had significantly more blood loss compared with patients with hypo-vascular tumor among mini-invasive group.Conclusion: In selected cases with spinal metastasis, minimally-invasive tubular surgery is safe and effective for patients with spinal metastasis. Patients with hypo-vascular tumor were more suitable for this technique with less blood loss, less blood transfused, less drainage and shorter postoperative hospitalization.

A COMPARISON OF THE TOMITA AND TOKUHASHI SCORES IN SPINAL METASTASIS

ABSTRACT Objective To compare Tokuhashi and Tomita scores in patients with epidural spinal metastasis who underwent surgical treatment. Methods A retrospective evaluation of 103 patients with spinal metastasis and epidural compression who underwent surgical treatment. An analysis was performed of agreement between the survival rates observed in the study sample and the survival rate estimated by the Tomita and Tokuhashi scales. Results The overall accuracy was 39.03% for the Tomita scale and 61.75% for the Tokuhashi scale. Fair agreement (0.38 weighted Cohen’s Kappa coefficient) was observed between patient survival and the Tokuhashi score, and slight agreement (0.25 weighted Kappa coefficient) for the Tomita score. The agreement for both scales was higher for patients with less than six months’ survival, with general accuracy of 79.17% for the Tomita and 70.59% for the Tokuhashi scoring system. Conclusion There was fair and slight agreement between the Tokuhashi and Tomita scores with patient survival group. The agreement was higher for patients with less than six months’ survival. Level of evidence III; Comparative retrospective study.

Sarcopenia as a Prognostic Factor for 90-Day and Overall Mortality in Patients Undergoing Spine Surgery for Metastatic Tumors: A Multicenter Retrospective Cohort Study

BACKGROUND Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. OBJECTIVE To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. METHODS A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. RESULTS Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. CONCLUSION In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

Modified score based on revised Tokuhashi score is needed for the determination of surgical intervention in patients with lung cancer metastases to the spine

Background Revised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction. Methods Our study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan–Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves. Results Targeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved. Conclusions The modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.

CMET-15. SARCOPENIA INDEPENDENTLY AND STRONGLY PREDICTS SURVIVAL IN PATIENTS UNDERGOING SPINE SURGERY FOR METASTATIC TUMORS

INTRODUCTION Predicting survival and surgical morbidity in patients with spinal metastases would help guide clinical decision making and stratify treatments between surgical intervention and palliative care. This multi-center retrospective cohort study evaluates whether the frailty/sarcopenia paradigm, as measured by psoas size, is predictive of survival in patients undergoing surgery for spinal metastasis. METHODS 271 patients from four institutes who had undergone surgery for spinal metastasis were identified. Morphometric measurements were taken of the psoas muscle at the L4 vertebral level < 200d from surgery. Mortality hazard ratios were calculated using multivariate analysis, with variables included from past medical history, type and extent of tumor spread, type and intensity of surgery, and postoperative chemotherapy or radiation. RESULTS Psoas size was predictive of overall mortality; patients in the smallest tertile had shorter overall survival compared to the middle (OR 0.52, p< 0.001) and largest tertile (OR 0.45, p< 0.001). Psoas size predicted overall mortality more strongly than Tokuhashi score (OR 0.91, p= 0.010), Tomita score (OR 1.07, p= 0.04), and KPS (OR 0.99, p= 0.58). Psoas size was also predictive of 90-day survival; patients in the smallest tertile had shorter 90-day survival compared to the middle (OR 0.24, p= 0.003) and largest tertile (OR 0.16, p= 0.001). Psoas size predicted 90-day mortality more strongly than Tokuhashi score (OR 0.73, p= 0.002), Tomita score (OR 1.00, p= 0.92), and KPS (OR 0.98, p= 0.39). CONCLUSION In patients undergoing surgery for spine metastases, psoas size as a surrogate for frailty/sarcopenia predicts 90-day and overall mortality, independent of demographical, functional, oncological, and surgical characteristics. The sarcopenia/frailty paradigm is a stronger predictor of survival at these time points than the Tokuhashi score, Tomita score, and KPS. Psoas size can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

Elevated plasma cell-free DNA copy number variations to predict survival for cancer patient with spinal metastasis.

e14522 Background: Approximately 70% of patients with cancer have evidence of spinal metastatic disease at the time of their deaths. The spinal column is the most common location among osseous sites for metastatic deposits. Expected overall survival is the major determinant of treatments for those ones suffering from intractable pain, neurologic deficits, and even paralysis. We sought to evaluate copy number variations (CNV) in spinal metastatic cancer via cfDNA and determine if CNV is associated with prognosis and treatment decision. Methods: In this study, 314 patients with pathologically confirmed spinal metastatic cancers were recruited since November 2015. 314 plasma samples were sent to low-coverage genome-wide sequencing of cfDNA from plasma followed by a customized bioinformatics workflow UCAD. Tokuhashi score was also evaluated for each patient before surgery. Statistical correlation with clinical index like prognosis was estimated. Results: 280 evaluable data were collected (34 samples failed Quality Control). The median follow-up time is 276 days. 114 (40.7%) patients died during follow up till December the 25th, 2018. Elevated CNVs was found in 109 (38.9%) patients, including 9(69.2%) head&neck, 15(46.9%) liver and gallbladder, 27(44.3%) lung, 7(38.9%) breast, 2(28.6%) prostate, 5(19.2%) thyroid cancer, 4 (10.5%) kidney and 20(40.0%) cancer with unknown primary site. Further analyses showed that patients with elevated CNVs were found with worse survival. The median overall survival (OS) was 298 (95% CI: 258-422) days, as compared with those low-CNVs status with median OS 657 (95% CI:433-NA) days (Hazard ratio = 3.73 [95% CI: 2.22-6.27], P < 0.01). Especially for patients with low Tokuhashi score (≤8) who have the predictive survival less than 6 months, CNVs score distinguish those well-prognosis patients with median OS 433 (95% CI: 308-NA) days from the worse survival group with median OS 285(95% CI:243-348) days (Hazard ratio = 2.42 [95% CI:1.38-4.25], P = 0.013). Conclusions: We present the largest cfDNA genomic characterization of spinal metastatic cancers. Specific CNVs features are enriched in spinal metastasis cancers with different primary sites. Elevated CNVs in plasma cfDNA is significantly associated with worse survival in a large spinal metastatic cancer cohort. This demonstrates that cfDNA CNVs could be a useful marker in estimating the survival time of spinal metastasis cancer patients for whom the outcome is mainly dependent on the selection of proper treatment.