| Summary of study backgroundSpine vertebral column tumors incidence are approximately6%～10%of all bone tumors, cancer metastatic lesions are the most common with incidence of45%～75%of all spinal neoplasms, whereas primary malignant tumors rate for15%～25%and primary benign tumors account for10%～20%of all spinal neoplasms. Spinal tumors have a diverse range of aggressiveness ranging from benign lesions to highly infiltrative malignant tumors causing significant pain, neurological morbidity and negatively impact patient’s quality of life and survival. The aim in treating metastatic spine lesions is to provide patients with improved quality of life through controlling pain and achieving partial or full functional recovery. Many studies have demonstrated that suitable surgical resection of primary spinal tumors with adequate margins results in improved local disease control and survival, thus, the overall benefits and risks of surgical treatment in spinal tumors patients, the overall impact of each on the overall health must be assessed, and that was the aim of the first part of our study.Increasing life expectancy of patients with spinal metastases has resulted in seeking for better overall quality of life. The prognosis of patients with spinal metastasis is not very promising and hard to predict. Although there are many scales such as Revised Tokuhashi prognosis scoring system (RTSS) and Tomita score which attempt to help predicting metastatic patient prognosis and to guide management of spinal metastasis, their real applicability is unsure. In the second part of this study we sought to determine the practicability of these scores, we also sought to identify factors that may influenced prognosis and survival in spinal malignancies.Study design:Retrospective clinical study of123patients with primary spine tumors and86patients with spinal metastases underwent surgical treatment at HUST Tongji Hospital Orthopedic Spine Surgery Department from31December2003to31December2013. Study objectiveslrd part study purpose:1-To assess overall clinical outcomes in patients with extradural vertebral spinal tumors (primary spine tumors and spinal metastasis) whom underwent surgical treatment and to discuss surgical options that applied, Moreover to discuss postoperative complications, tumor recurrence and related factors, all to make suggestions for better treatment options in managing spinal neoplasms and for future research reference.2-To valuate the reliability of Tomita classification, Enneking staging and WBB zonation and their clinical practicality in managing spinal tumors.3-To analyse overall survival of patients with spinal and to investigate progression free survival (FPS) on primary tumors of the spine after surgery.2rd part study purpose:1-Survival analyzation for patients with spinal malignancies.2-To valuate the the applicability of Tomita prognosis score and RTSS in vertebral metastasis patients who surgically treated by calculating the actual average survival time and compare the results with two systems estimated life expectancys.in order to apply their prediction to treatment decision making.3-Univariate and multivariate survival analyses to primary malignant and metastases of the spine column.Study materials and methods1. Enrollment criteria:1-Patients with epidural spine column spinal bony neoplasm surgically managed at our hospital orthopedic spine surgery department from31December2003to31December2013.2-Tumors without vertebral encroachment or tumors only accept biopsy diagnostic operation was rolled out this study.3-Postoperative tumor specimen pathological study diagnosis conformation.4-The imaging studies done could identify Enneking grade and could localize the tumor according to Tomita classification&WBB zonation, together with other diagnostic procedure determining the primary site and if there any metastatic sites.2. Data collection:We retrospectively collected pre-and postoperative medical records clinical data of Amount of209cases according the criteria, Grouped into A, B, C three groups: Group A with86cases of spinal metastases, Group B with41cases of primary malignant spine tumors and Group C with82cases of primary benign spine tumors, there were130males (62%) and79females (38%). All cases were hospitalized then submitted to the same clinical and imaging workup and managed surgically, Followed-up period ranged from6months to10years (mean37.7months), the median age at surgery was46years (metastasis55.5years; primary malignant50years; primary benign37years).1-preoperative, postoperative and Followed-up outcome measures was obtained:Pain Visual Analog Scale(VAS), McAfee pain score.Neurological Function Frankel Score, the Karnofsky Index of performance status (KI), the Eastern Cooperative Oncology Group Functional status (ECOG) and HRQol EuroQoL5Dimensions(EQ-5D). In addition, at follow-up some patient was radiographically evaluated.2-Identified and recorded documented preoperative tumor Enneking stage, Tomita classification&WBB zonation for primary tumors, and preoperative Tomita prognosis score, RTSS score, the primary site and if there any metastatic for metastases patients,record surgical procedure materials for each patient.3-For those who didn’t survived at follow-up, the death time and cause was pursued as much as possible.Only spinal metastatic and primary malignant tumors of the spine enrolled the second part of this study:1-Overall survival was assessed using Kaplan-Meier survival analysis.2-Predictive scoring was done to patients with metastasis tumors according to the Tomita and RTSS prognosis scoring systems. A validation applicability study was done to these two systems by drawing the ROC curves and Spearman’s correlation analysis and then stepwise logistic regression to compare the actual survival with the life expectancys estimated by two systems.3-Univariate Kaplan-Meier survival method analysis and Multivariate COX regression model analysis was done to11factors may influence the metastatic spinal tumor and9factors my associated with the survival of primary malignant tumorsStatistical methodsThe main software tools was SPSS v20and MedCalc v12(The significance level established as p<0.05)1. Measurement data:t-test, and variance.2. Survival analysis:Kaplan-Meier method, corresponding K-M survival curve graphics and spearman correlation (α=0.05).3. Multivariate analyzing:COX regression (Backward). ResultsExcept for56cases, a mean follow-up of37.7months (range,6to120months) for other153cases at FLUP rate of73%(73.2%) was accomplished.Most of the metastatic tumors were from internal organs, gastrointestinal and unkown sources at onset. Metastases from lung cancer accounted for30%, liver10%, kidney8%, gastrointestinal8%, prostate6.5%, thyroid6.5%,breast4%, others14%whereas unknown primary was13%,. The period of symptom onset in three groups within3months and6months were (A group:63%,84%; B group:51%,63%; C group:35%,62%) respectively; Most of the malignant primary tumors were plasmocytoma, myeloma and chondrosarcoma; Most of the benign primary tumors were osteoangioma, giant cell tumor and osteoblastoma. The dominant symptoms were pain and neurological defect. The tumor involvement on more than one vertebrae in three groups rating as (3.5%,2%,1.8%) respectively. All tumors were mostly found in the thoracic spine (42%). Three groups’patients were treated by different combinations of operative methods mainly wide and marginal resection. The rate of misdiagnosis which mainly occurred in the metastatic tumor group was2.3%.lrd part study resultsAll outcome measures marked improvements in pain and HRQoL in both short-term and long-term phases.①Pain evaluation:The mean VAS pain scores attained to (2.7,2.6,0.96short-termly) and (3.2,3.3,1.2long-termly) compare to (7.6,7.4,6.2) preoperatively (P=0.000), and mean McAfee pain scores improved to (0.8,0.7,0.2short-termly) and (0.9,0.9,0.6long-termly) compare to (2.9,2.8,2.2) preoperatively (P=0.000)②Performance status evaluation:The mean Karnofsky score was (82,83,94short-termly) and (80.6,87.5,94.8long-termly) points compare to (65,66,73) points PREOP. Karnofsky score was significantly improved (P=0.000)③HRQoL evaluation:The mean EQ-5D score was (0.26,0.22,0.07short-termly) and (0.3,0.25,0.07long-termly) points compare to (0.5,0.48,0.38) points. PREOP. EQ-5D score was significantly improved (P=0.000)④Functional status evaluation:The mean functional score (ECOG) was (1.5,1.4,1.39short-termly) and (1.6,1.1,0.4long-termly) points compare to (2.5,2.6,2.1) points PREOP. ECOG score was significantly improved (P=0.000) ⑤Neurologic function evaluation(Frankel score):Only (3.3%) of156followed-up patients (2.3%,4.9%,1.2%) with motor deficits were worsened postoperatively, whereas93(60.8%) improved at least one Frankel grade.35.9%of the patients [55cases (E:48, D:2, C:1, B:1,A:3)] was retained during follow-up(P<0.0001).⑥Complications were recorded at a level of11.5%. Short-term complications(≤6months): Incision-related complications:wound malhealing, leaks, malunion and infections;11cases(5,3,3)(5.3%),4cases (1,1,2)(1.9%) had Neurological complications include local weakness, local paralysis and sphincter dysfunction, one case (1,0,0)(0.5%) had complete paraplegia, one case (0,0,1)(.5%) had intraoperative bleeding, one case(0,0,1)(0.5%) had systemic complications (0,0,1)(lung embolism. Surgical related complications was4cases (1,2,1)(1.9%);2cases was C.S.F leakage, one was pleural effusion and the forth was cage loosening.Long-term complications:Among153followed-up there was one case (0.5%) unstable cage fixation; cage loosening and one case (0.5%) had PMMA reactive inflammation.⑦Tumor Recurrence and Metastasis:Rolling out the dead cases, the recurrence rate on three groups’followed-up patients was (9%,19%,11.6%) and3cases (7%) of primary malignant had metastasized after surgery.⑧PFS mean time of primary benign tumors was16.5±10.4months, median10.5months, the progression mainly occurred in osteoblastoma and osteoid osteoma tumors cases and some implants related complications, however the PFS line was75%after6years.2rd part study results①For primary malignant spinal tumors the patients had a median age of50years and a median survival of46months after surgery. And for spinal metastases the patients had a median age of55.5years and a median survival of10months after surgery.②The K-M survival analysis showed the actual survival time of subgroups4-5and8-10points of Tomita were within expected life expectancy. While subgroups2-3points and6-7points had a20.7months median survival time, was less than expectancy (P<0.05), as for RTSS, the subgroup0-8which the median was6months which is the upper bound of expected life expectancy (<6months), subgroup with9-11score actual survival was higher than expect survival and12-15was within expected life expectancy (P=0.001).③ROC curves revealed there in no significance difference between RTSS and Tomita score accuracies (P>0.05) estimated survival and the actual survival, but two scores ROC line was above the baseline, relatively high prognostic accuracy in RTSS in period "death within6months" and Tomita score in the periods which the life expectancy more than one year, spearman’s correlation study showed RTSS was positively correlated with survival time while Tomita score was negatively.RTSS correlation coefficient(R=0.414) is larger than Tomita (R=0.339), However, the two scores were much lower than the0.6-0.8).④Stepwise logistic regression revealed that in the poor score (survival within6months) and good score (survival>12months) RTSS is more accurate and suitable predictor than Tomita whereas moderate scores (survival12-24months) Tomita score better than RTSS.⑤For spinal metastases, the univariate analysis revealed that the source of primary tumor, Tomita classification,Tomita surgical score,RTSS were associated with survival (P<0.05). multivariate analysis showed that the pathological of tumor, Tomita classification were independent predictors of survival, specially the pathological type and malignancy degree (P<0.05), and for primary malignant spinal tumors the univariate analysis and multivariate analysis revealed that Gender, the Pathological type of primary malignant neoplasm, Enneking grade were associated with survival specially the pathological type and malignant degree (P<0.050).Statistic results①Neurologic function statement statistics:Preoperatively (26.7%,26.8%,8.5%) were non-walkers (Frankel A-C),(24.4%,31.7,23.2%)could walk with aids (Frankel D) and (48.8%,41.5%,68.3%) had normal motor function (Frankel E).The followed-up patients’ neurological functions was improved:(12.7%,10.3%,3.3%) were non-walkers (Frankel A-C),(14.3%,17.2%,3.3%)could walk with aids (Frankel D) and (73%,72.4%,93.4%) had normal motor function (Frankel E). Five of153followed up (3.27%) patients (A,B,C:2.3%,4.9%,1.2%) with motor deficits were worsened postoperatively, whereas93(60.8%) improved at least one Frankel grade.35.9%of the patients (55cases (E:48, D:2, C:1, B:1,A:3))was retained during follow-up.②Surgery statistics:Surgical approaches; posterior (42,22,56); anteroposterior combined (19,11,7); antero&anterolateral (21,1,11); posterolateral (4,7,8) approaches. Oncological margins operation methods:Intralesional (0,0,21); Marginal en bloc (48,23,42); wide en bloc (18,17,15); Palliative (18,1,0); PVP&PKP (2,0,4)③Survival statistics:spinal metastases and primary malignant spine tumors3months survival rate was (80%,92%),6months survival was (73%,90%)1year survival was (32%, Spinal metastases overall median10months, the maximum survival time was6.1years (F,51y, thyroid follicular carcinoma) still alive, the minimum was one month. Whereas primary malignant spine tumors overall survival median46months, the maximum survival time was6years (F,19y, chondroblastic osteosarcoma) still alive, the minimum survival was only one week (F,42y,plasmocytoma).Conclusions1-Surgery for patients with primary bony tumors of the spine can offers radical cure, relief pain, function recovery and improved quality of life with low rates of complications and recurrence. Surgical intervention in patients with spinal metastatic has a positive impact on the patient’s overall health and function; many factors have influenced the outcome of surgical treatment. The most important is the tumor pathological characteristics.2-Results indicate substantial and near-perfect reliability for both Enneking and WBB classification in terms of staging and guidance for spinal tumors surgical treatment.3-Determining the tumor characteristic before deciding surgical treatment, recognizing the risk factors for postoperative complications, better preoperative preparation, carefully surgical planning and operative tactic, operation time controlling, extreme care in handling soft tissues, adequate exposure, full division and carefully fixing suitable stabilization technique all are the guarantees to reduce and prevent complications and to reduce the tumor recurrence.4-Because the rarity of primary tumors of the spinal column, it’s necessary to develop multicentre studies with a uniform data gathering tools to establish principles about the behavior of these lesions and their appropriate treatment, emphasized health education is away to decrease lung and liver cancers which they are male predominance causing by healthy-harming habits therefore minimize spinal metastases incidence.5-Both Tomita and RTSS survival prognosis systems have potentially merit when deciding the suitability and method of the surgery for patients with metastatic spinal disease. RTSS is reliable for life-expectancy estimation for rapid growth cancers and more accurate in differentiating between poor and good prognoses patients, whereas Tomita is less sensitive for early mortality and suitable in differentiating moderate prognoses, we recommend apply both two systems scoring metastatic spinal patient after admission,0-8and12-15tow subgroups in RTSS and4-5subgroup in Tomita are relatively more precise in predict survival than other subgroups. tumors patients with good and moderate life expectancy. For those who have poor life expectancy, the urgent treatment of vertebral metastasis still remains paramount to protect spinal cord vitality. Surgical decision criteria should be based on clinical and neurological disorders rather than prognostic scales for those individuals.7-The source of primary tumor, Tomita classification, Tomita score, RTSS are associated with survival in metastatic spinal tumors, the pathological of tumor, Tomita classification are independent affecting the spinal metastases patient’s survival, specially the pathological type and malignancy degree. The pathological type of primary malignant tumor, Enneking grade are the factors affect prognosis specially the pathological type and malignant degree. |
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