Survival analysis amongst patients with metastatic spine tumor treated with corpectomy

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1 ISSN X Kręgosłup i klatka piersiowa Survival analysis amongst patients with metastatic spine tumor treated with corpectomy Analiza przeżyć pacjentów po korpektomiach wykonanych z powodu guzów przerzutowych kręgosłupa Piotr Biega, Grzegorz Guzik, Tomasz Pitera Oddział Ortopedii Onkologicznej Szpitala Specjalistycznego w Brzozowie Podkarpacki Ośrodek Onkologiczny Abstract Introduction: Spine metastasis are found In 30% of ontological patients. Approximately 10% of the patients with spine metastasis suffer from decline In neurological function. For those patients surgical decompression is treatment of choice. The vertebral body is common involved by metastatic tumor. Corpectomy allow to remove tumor. However after procedure reconstruction of the vertebral body is necessary. Aim: Aim of the study are analysis of treatment results of the patents with spine metastasis after corpectomy. Material and methods: Retrospective analysis of 51 patients records with metastatic spinal cord compression treated with corpectomy were preformed. Those patients underwent surgical debunking of the vertebral body with implantation of the vertebral body prosthesis. All patients were operated between 2014 to 2015 In The department of Orthopaedic Oncolog of The Podkarpackie Oncological Center In Brzozów. Most of patients were men (61%). Mean age was 61 years. The most common origin of metastasis was Brest. Mean observation time vary from 9 to 920 days. Results: In postoperative period neurological status improve In 71% of patients. Pain reduction was achieve. Mean VAS reduction was 4.26 point. Functional improvement was also noted. Karnofsky score improve by 16 point. Mean survival was 16 month. Complication rate was 16%. One patient (2%) suffer from wound infection. Future neurological impairment was detected In 7% of patients. Conclusion: Corpectomy is safe and sufficient method of treatment for spine metastasis. The origin of cancer and it s advanced influence survival. Multilevel involvement increase operations time and reduce patients survival. Key words: gtumors, spine, metastasis, treatment, survival, corpectomy Streszczenie Wstęp: Przerzuty nowotworów złośliwych do kręgosłupa dotyczą 30% pacjentów onkologicznych. Około 10% chorych z przerzutami do kręgosłupa doświadcza pogorszenia stanu neurologicznego. W tej grupie pacjentów leczenie operacyjne powinno być postępowaniem z wyboru. Większość guzów przerzutowych kręgosłupa lokalizuję się w trzonach kręgów. Korporektomia pozwala na usunięcie guza w całości lub w znacznej części ale wymaga odtworzenia powstałego ubytku kości przy użyciu cementu lub protezy. Cel pracy: Celem pracy była analiza wyników leczenia pacjentów poddanych korporektomii z powodu guzów przerzutowych. Materiały i metody: Wykonano retrospektywną analizę przebiegu leczenia 51 pacjentów z guzami przerzutowymi kręgów powodującymi ucisk rdzenia kręgowego i deficyty neurologiczne. U chorych resekowano przerzuty wraz z trzonami kręgów uzyskując dekompresję rdzenia kręgowego a następnie implantowano protezy kręgów. Materiał obejmuje pacjentów operowanych w Oddziale Ortopedii Onkologicznej w Brzozowie w latach Większość chorych stanowili mężczyźni (61%). Średni wiek (zarówno mężczyzn i kobiet) wynosił 61 lat. Najczęściej zmiany przerzutowe powodował rak sutka (28%). Czas obserwacji wynosił od 9 do 920 dni. Wyniki: W okresie pooperacyjnym stwierdzono poprawę funkcji neurologicznych u 71% chorych. Uzyskano redukcję natężenia bólu o 4,6 jednostki VAS i poprawę funkcjonalną chorych w skali Karnofsky ego o 16 punktów. Średni czas przeżycia wynosił 16 miesięcy. Odsetek powikłań wynosił 16%. Pooperacyjne pogorszenie funkcji neurologicznych odnotowano u 7% chorych. U jednego (2%) pacjenta stwierdzono opóźnienie gojenia rany operacyjnej. Wnioski: Korpektomia jest skuteczną i bezpieczną metodą leczenia guzów przerzutowych. Przeżycie pacjentów zależy głównie od punktu wyjścia i zaawansowania nowotworu. Zmiany wielopoziomowe powodują wydłużenie czasu operacji i skrócenie okresu przeżycia pacjentów. Słowa kluczowe: guzy, kręgosłup, przerzuty, operacyjne, przeżycie, korpektomia. Author s address: lek. Piotr Biega, ul. Daszyńskiego 3/11, Sanok, tel.: , ap.biega@gmail.com Received: Accepted: Published:

2 Introduction The spine is the most common site of bone metastasis. While almost every cancer can metastaise to bone. Breast, lung, prostate and kidney account for 80% of all bone lesion. [1,2]. Improvement in diagnostic modalities and systemic treatment had led to increase in survival periods in cancer patients. Therefore metastatic bone disease with led to intractable pain, pathological fracture, spine instability and neurological deficit gain in importance. Surgery can restore and preserve neurological function, spine stability and decrease mortality morbidity and increase quality of life [4,5,6]. Between 2000 to 2009 number of spine surgery due to spine metastatic tumor increase by 60% [7]. Plausible treatment options for metastatic spinal tumor patients include chemotherapy, radiotherapy, vertebroplasty, or operation[8]. Selection appropriate treatment depends on patients general status, origin of metastasis, number of metastasis and its location [9]. To guide treatment recommendation various scale were proposed (Tomita, Tokuhasi, Bauer, van Bollen, Gasbarrini) [10]. Up to 70% of the spine metastasis located in the vertebral body. Therefore only corpectomy or en bloc resection allow to remove tumor. Corpectomy is indicated in patients with single involvement of the 2-3 adjacent vertebral body, and survival prognosis more than 6 mouth. [11]. There are few studies regarding treatment results of corpectomy amongst patients with cancer. Available study analyzed small population of patients, with metastases located in the thoraco-lumbar spine. Moreover patients in these studies had single level involvement, whereas in clinical setting 50% of metastatic tumors had multilevel involvement [12]. In our study we analyzed results, complication, and functional results of corpectomy amongst 51 patients with metastatic bone disease. Material and methods We performed retrospective analysis of the 51 medical records of the patients with metastatic spine tumor, which underwent corpectomy in our hospital. Database include patients receive one or more level corpectomy followed by prosthesis implantation and posterior stabilization in single institution between 2014 and The indication for surgery was intractable pain, neurological deficit, unstable pathological fracture. Additional all patients were evaluated by multidisciplinary team prior operation to assess possibility of radiotherapy or systemic treatment and predicted survival time. Based on medical documentation and radiological finding clinical characteristics of the patients were created. Preoperative and postoperative pain intensity was assessed by VAS scale (Visual Analogue Scale), functional status was assessed by Karnofsky scale and neurological function was assessed using Frankel grade system. Additional operation time, blood lost, survival, complication and hospitalization time were analyzed. Normally distributed continuous variables were presented as means ± standard deviations. Variables with a skewed distribution were expressed as medians with lower and upper quartiles. The intergroup differences were tested using Student s t-test. The categorical variables were expressed as numbers with percentages. The inter-group differences were tested using the c2 test. Survival analysis was performed by Kaplan-Meier method. A value of p < 0.05 was considered statistically significant. Statistical analyses were performed using the STATISTICA 10 data analysis software system (StatSoft, Inc.). Operation procedure Position of the patient and selected approche depends on tumor localization. The cervical spine lesion (C3-Th2) was managed by anterior approach, with longitudinal incision along sterno-cleido-mastoideus muscle. The upper thoracic spine (Th3-Th6) was managed by posterolateral approach. The thoracolumbar spine lesion (Th7-L5) was managed by thoracophrenico lumbotomy or lumbotomy approach. The reconstruction was performed by placement of an expandable titanium cage (Vlift; Stryker,Kalamazoo, Michigan USA) and lateral stabilization by two pedicle screw above and below a pathologic level in the thoracolumbar spine. Whereas in the cervical spine reconstruction was performed by ECD (Expandable Corpectomy Device Synthes), with anterior plate stabilization. We don t use bone grafts for reconstruction. The drainage was maintained for 5 days in the retroperitoneal space and 7 day in the pleural cavity. The patients were bring to upright posture after two days. Results Most of the patients were men (61%). Mean age of women were ,2, and men were ,2. Mean observation time was 422 (od 9 do 920) days. Tabel 1 clinical characteristic of the study population. 171

3 Tabel 1. Clinical characteristic of the patients with the spinal metastatic tumor treated with corpectomy (N=51). Variables Age [years] 60,5±12,7 Operation time [min] 124 (45-315) Volume of blood transfusion [ml] 760 ( ) Hospitalization time [days] 14,3±6,72 Observation time [days] 422 (9-1087) Blood transfusion 31 (61) Multilevel involvement 23 (45) Sex [Men] 31 (61) Spine portion Cervical 7 (14) Thoracic 26 (51) Lumbar 18 (35) Origin of the metastasis Myeloma 14 (27) Prostate 9 (18) Kidney 8 (15) Breast 6 (12) Lung 5 (10) Gastrointestinal 5 (10) Larynx 2 (4) Urethra 1 (2) Thyroid 1 (2) The primary sites of the metastatic tumors were as follows: myeloma (27%), prostate cancer (18%), kidney cancer (15%), breast cancer (12%), and lung cancer (10%). In 8% of the patients visceral metastasis were diagnose. The spinal metastases were first sign of cancer diseases in 31% of patients. Localization of the spinal lesion presented as follows: the cervical spine 12%, the thoracic spine 47%, the thoracolumbar spine 6% and lumbar spine 35%. According to Tomita scale most of the spinal tumor were assessed as T6 (76%). After surgery mean VAS score was 3,72 and was decreased by 4.26 point (p>0.05). Functional status of the patient asses according to Karnofsky score was 70 after surgery and rose by 16 point (p<0.05). Neurological status improve in 69% and increased by an average of 2 grade in Frankel scale. Median survival was 483 days ( ). Overall survival was 36%. Highest survival rate was noted amongst patients with myeloma 54%, and lowest in patients with lung cancer(0%) Figure 1. Number of involved level had no influence on survival. The mean procedure duration was 149 ( ) minute. Mean blood loss was 1445 ( ) mililiter, and was highest in patient with melanoma. Estimated blood loss expressed as a hemoglobin reduction was 2,15 g/dl±1,58. In postoperative period 61% required an average of 2 units (0-8) of blood. Highest hemoglobin reduction was note amongst patients with kidney cancer. In one-way ANOVA analysis of hemoglobin reduction in the patients with different cancer origin did not show significant correlations. However subgroup indicated higher reduction in kidney cancer compared to other groups Figure 2. Fig. 1. Survival time by orygin of the methastasis. Clinical characteristic of the patients by number of involved levels Tabel 2. The patients with multilevel involvement compared to single level metastatic tumor need longer operation. Mean hospitalization time was 14 ± 6,7 days. In eight (16%) patients complication were noted. Declination in neurological function were observed in 4 (7,8%) patients. However despite MRI scans and revision we didn t found underlay condition of it. Two patients had minor wound infection, and one had pleural abscess. One patient died within 30 day after operation. Tabela 2. Clinical characteristic by number of involved level. Variabel [unit] Singiel level N=28 Multi level N=21 Age 60,5 62,23 Main tumor orygin Myeloma 25% Myeloma 33% Main localization Lumbar 50% Thoracic 61% Operation time [min] * reduc- Hemoglobin tion [mg/dl] Transfusion [ml] volume 2,08 2, VAS reduction 4,2 4,9 improve- Karnofsky ment Hospitalization [days] 13,2 14,89 172

4 Discussion Corpectomy with subsequent reconstruction of the vertebrae body using prostheses allows to restore height, spine curvature and reduce sagittal deformity. Also significant cytoreduction can be achieved (50-80%)[13]. Compared to posterior decompression, the anterior approach increases the rate of improvement in neurological status, up to 71% of patients[14]. Tomita et al. indicate a prolonged survival of patients treated with corporectomy by 11.4 months[15]. A direct comparison of survival of the patients undergoing different types of surgical treatment is rarely considered because the expected lifetime, estimated using prognostic scales, is one of the main parameters eligible patients for a particular surgical treatment. The quality of life of patients with metastatic spinal tumors correlates with the functional score obtained in the KPS, Frankel scale and the intensity of pain asses by VAS score[5,16]. Corpectomy like other surgical techniques, can achieves a reduction in pain. In the our study pain reduction by 4.26 VAS point was noted. Similar results presents Jouberta et al.[16] and Chonga et al.[17], which had pain reduction ranging from 3.2 to 6.3 in VAS scale. Neurological status was improved in 68% of the patients, whereas in 24% preoperative and postoperative neurologic statuses did not differ. Similar neurological improvement was reported in available in literature range from 20% to 90% [5,18,19,17,20,21]. Ruiter et al. show neurological improvement only in 20% of patients, however in this study patients had more severe spinal cord compression asses according to Frankel system [20]. Only one study of Ruiter et al. assess functional status by Karnofsky score. Similar to his study after operation we noted increased by 16 points in Karnofsky score [20]. Moreover Ruiter et al. indicated that pain asses by VAS, functional status asses by Karofsky and spinal cord injury asses in Frankel grading system correlate with quality of life [20]. Mean survival time was 16 months and these outcomes were comparable with those reported in a literature (Shen et al. 16 months [21], de Ruiter 14 months [20], a Jobert 17 months [16]. At final follow up 35% of patients were alive. Origin of cancer, neurological status and multilevel involvement affect survival [19,23]. Also tumor mass, and pathological fracture has influence on survival [22]. In the our study visceral metastasis do not affect survival. Death within 3 months after surgery range from 6.8 to 17%. In the our study 8% of the patients died within 3 months [17,19,23]. According to literature complication after corpectomy is as high as 60% [23]. With the development of techniques for reconstruction of vertebral body with prosthesis instead bone cement the number of complications systematically decreases [23]. Recently complication rate vary from 4 to 14,3% [5,16,21,]. De Ruiter et al. show reduction of infectious complication from 10% to 4% and neurological complication from 12% to 0% within 3 years [5]. Also mean operation time decrease by 2.2 hours and one hour in Jansson [5,15]. Those observation indicated that corpectomy should be performed by surgeon familiar with that technique. Lau et al. show that complication rate and hospitalization time can by future decrease be employment of mini-invasive technique for corpectomy [23]. The most common complication after corpectomy is infection (2,5-16%) [52]. Compare to posterior stabilization number of infection is similar [5,25,26]. However anterior approach is endangered with vascular insult ( %) [27] and mechanical instability with cage subsidence (1.7-21%) [20]. The risk of infection is associated with blood loss and in posterior stabilization with number of stabilization levels [22,25,26,28]. Mean operation time of 120 minutes and complication rate of 16% is comparable with other study [15,16,21]. The most common complication amongst our patients were neurological deterioration after surgery (7,8%). Jansson et al. reported 4,7% [19], Shen 5% [20], de Rutier 12% [21] of future neurological decline after surgery. However compared to rest of the authors we perform operation in patients with compression lasted longer than 48 hours ( range from 4 days to 2 months). Conclusions 1. Corpectomy is an effective and safe method of treating metastatic spinal tumors. 2. Survival of patients depends mainly on the origin of the tumor. 3. Multi-level changes dominate. There was no effect of the multilevel involvement on the outcome of the treatment, apart from prolongation of the operating procedure. References [1] Zaikova O, Giercksky KE, Fossa SD, et al. 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