Ann Surg Oncol DOI 10.1245/s10434-014-3754-y
ORIGINAL ARTICLE – NEURO-ONCOLOGY
Partial Tumor Resection Combined with Chemotherapy for Multiple Myeloma Spinal Cord Compression Jun Qian, MD1, Juehua Jing, MD1, Dasheng Tian, MD1, and Huilin Yang, MD2 1
Department of Orthopaedics, The Second Hospital of An Hui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China
ABSTRACT Background. Some controversies about the optimal therapy for multiple myeloma (MM) spinal cord compression are still presented. This study was conducted to investigate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression. Methods. Eleven patients were diagnosed with MM spinal cord compression. Radiological examinations manifested 12 spinal lesions on 11 patients. All patients were treated with partial tumor resection with adjuvant chemotherapy. The mean procedure time, the mean blood loss, visual analog scale score, Oswestry Disability Index (ODI) score, neurological status, complication, recurrence, and quality of life were evaluated. Results. Eleven patients were followed up with a mean of 25.1 months. The mean procedure time was 152.6 ± 30.4 min, and the mean blood loss was 396.4 ± 82.7 ml. Overall pain control rate was 89 %, with complete pain relief in 64 %, and partial pain relief in 25 %. The median pre-ODI values of 85 % significantly improved to 12 % at the last follow-up. Neurological improvement of one to two grades was observed 6 months postoperatively. Complications included pleural effusion, titanium cage loose, and thrombocytopenia in three patients each. Local recurrence was 18.2 %. One patient died of pulmonary infection. Quality of life improved from 39 % before surgery to 81 % in ten survivors at the last follow-up. Conclusions. Partial tumor resection combined with chemotherapy seems to be an effective treatment for MM spinal cord compression owing to the minor surgical trauma, fewer
complications, and effective pain control. Total resection of the tumor is not necessary for MM of the spine.
Ó Society of Surgical Oncology 2014
MATERIALS AND METHODS
INTRODUCTION Multiple myeloma (MM) is a hematological malignancy characterized by accumulation of monoclonal plasma cells. It accounts for approximately 1 % of all cancers and represents about 10 % of all hematological malignancies.1 It affects the bone marrow and presents as multiple osteolytic lesions with the most common localization being the spine.2,3 Pathological fracture of the vertebral body resulting in spinal cord compression is a common complication of this disorder.4 Spinal cord compression accounts for approximately 5 % of patients with MM.5 The first outstanding symptom is neck pain or back pain as MM attacks the spine, and the pain may be worse with movement.6 The spinal cord compression due to pathological collapse of the vertebral body by MM presents a progressive neurological deficit. This is the next most characteristic clinical sign of spinal MM.6 Traditional treatments of osteolytic vertebral collapse for pain control included bed rest, bracing, and analgesics.7 Surgical resection and radiation therapy were the main treatments for MM spinal cord compressions described in previous papers.7–10 Less experience with surgical treatment combined with chemotherapy for MM spinal cord compression was discussed. The aim of this study was to investigate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression.
First Received: 11 January 2014 J. Jing, MD e-mail: [email protected]
We have obtained the approval from the ethics committee of the second hospital of An Hui Medical
J. Qian et al.
University. All patients have provided written informed consent to participate in this study, and the ethics committee of our hospital has approved this procedure. Furthermore, our study meets the guidelines of the responsible governmental agency. Patients Eleven patients underwent partial tumor resection combined with chemotherapy for MM spinal cord compression between October 2008 and July 2012. There were women and eight men with a mean age of 60.3 years (range 47– 69 years). All patients complained of severe neck pain or back pain, numbness, and weakness of lower extremities between 3 and 17 months (average 5.8 months). Neck pain or back pain and neurological deficits gradually worsened during this time. Physical examinations showed neurological deficits resulted from spinal cord compression. Standard radiological examinations including X-ray, magnetic resonance imaging (MRI), and three-dimensional computed tomography (CT) were performed to prove the spinal lesion. X-rays showed 11 vertebral body fractures of whole spine on all patients, but 12 vertebral destructions and spinal cord compression at the same level were illustrated by MRI. Osteolytic lesions were located in the cervical spine in two patients, the thoracic spine in five patients, and the lumbar spine in four patients. Heterogeneous hyposignal in T1weighted spin-echo sequence and hypersignal in T2weighted spin-echo sequence were shown within the osteolytic lesion. Three-dimensional CT showed osteolytic destruction, expansive growth, and soft tissue mass. Emission computed tomography (ECT) revealed multiple bone involvements, except spinal lesions. Based on MRI and CT, it was strongly suggested that the spinal osteolytic lesion was caused by MM. According to the grade system developed by Tomita et al.11 three patients were classified as grade 4, six patients were grade 5, and 2 patients were grade 6. Laboratory studies including serum protein electrophoresis showed a Bence-Jones protein and a monoclonal hypergammaglobulinemia were positive in 11 patients. Bone marrow aspiration and biopsy confirmed MM (20 % abnormal plasma cells) in nine patients. Ten patients were diagnosed with MM and one patient was suspicious of MM by laboratory tests and bone marrow biopsy before treatment. Surgical procedures The surgical strategy consisted of decompression of the spinal cord and stabilization of the spine for pain control and neurological function recovery. Complete tumor
FIG. 1 A 67-year-old female patient presenting with a history of neck pain, numbness, and weakness of the lower extremities for 7 months was diagnosed as multiple myeloma spinal cord compression. We performed anterior decompression, corpectomy of the involved vertebral, removal of soft tissue mass that was creating spinal cord compression, iliac strut graft, and a cervical spine locking plate. a and b are T1 and T2 magnetic resonance images of the cervical spine before surgery, respectively. The vertebral body of C7 is destroyed and the spinal cord is compressed at the same level. c is ECT picture before surgery. d is an X-ray of the cervical spine after surgery
resection is not the primary goal of the surgery. We performed partial tumor resection and spinal fixation on all patients. Reconstructions were done with iliac bone graft and a cervical spine locking plate in two patients, iliac bone graft with titanium cage and posterior instrumentation in four patients, and iliac bone graft and posterior instrumentation in five patients. Anterior decompression, corpectomy of the involved vertebral, removal of soft tissue mass creating spinal cord compression, iliac strut graft, and a cervical spine locking plate were performed in the cervical osteolytic lesions (Fig. 1). We did not resect the outer edge within the tumor vertebral body for minor surgical trauma and less blood loss. Dorsal decompression, transpedicular partial tumor resection, iliac strut graft, titanium cage and pedicle screws were carried out in thoracic and lumbar lesions (Figs. 2, 3). The anterior edge and contralateral of decompression within the tumor vertebral body were not routinely resected like other malignancies.
Treatment of Multiple Myeloma Spinal Cord Compression
FIG. 2 A 49-year-old male patient presenting with a history of back pain, numbness, and weakness of the lower extremities for 4 months was diagnosed as multiple myeloma spinal cord compression. We performed dorsal decompression, transpedicular partial tumor resection, iliac strut graft, with a titanium cage and pedicle screws. a and b are T1 and T2 magnetic resonance images of the thoracic spine before surgery, respectively. The vertebral body of T4 and lamina of T3,4 are destroyed and the spinal cord is compressed at the level of T4. c is ECT picture before surgery. d is an X-ray of the thoracic spine after surgery
FIG. 3 A 47-year-old male patient presenting with a history of back pain, numbness, and weakness of the lower extremities for 11 months was diagnosed as multiple myeloma spinal cord compression. We performed dorsal decompression, transpedicular partial tumor resection, iliac strut graft, and used pedicle screws. a and b are T1 and T2 magnetic resonance images of thoracic spine before surgery, respectively. The vertebral body of L5 is destroyed and the spinal cord is compressed at the level of L5. c is a three-dimensional computed tomography (CT) picture before surgery. d is an X-ray of the lumbar spine after surgery
Postoperative care
together with oral dexamethasone (40 mg daily) for 4 days. This VAD chemotherapy was repeated every 21 days for four cycles.
All patients received alendronate therapy at an oral dose of 70 mg/week. An external spine brace was also used for the purpose of early ambulation.
Effectiveness assessment
Chemotherapy All patients were treated with chemotherapy 3 weeks postoperatively. Eight patients had undergone chemotherapy including bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of each 21-day cycle for four cycles, and together with oral dexamethasone (40 mg daily) on days 1–4, 9–12, and 17–20 for four cycles.12 Thalidomide was used in three of the eight patients. The starting amount of thalidomide was 100 mg/day, according to the patient’s condition, which was gradually increased to 200 mg/day. The other three patients were carried out by vincristine, doxorubicin and dexamethasone (VAD) chemotherapy.13 Vincristine (total dose 1.6 mg) with doxorubicin (36 mg/m2) over 4 days,
The following parameters were investigated to assess the efficacy: (1) the mean procedure time, (2) the mean blood loss, (3) VAS score, (4) ODI score, (5) complications, (6) recurrence, (7) neurological status,14 and (8) quality of life.15 Follow-up The follow-up methods consisted of questionnaires or personal contact with patients (either by phone or clinical investigation). Laboratory studies and radiological examinations, including MRI, were done to evaluate the patient’s condition, recurrence of spinal cord compression, stability of instrumentations, and bone graft fusion during the follow-up.
J. Qian et al. TABLE 1 Preoperative and postoperative characteristics of all patients Case Age Sex Symptoms (years)
Location Tomita Surgical treatment grade
Procedure Blood Chemotherapy time loss (min) (ml)
Recurrence Alive
1
53
M
Back pain, numbness, weakness
T9
6
Dorsal decompression, posterior fixation
215
631
Bortezomib, dexamethasone thalidomide
No
Yes
2
47
M
L5
5
Dorsal decompression, posterior fixation
186
359
Bortezomib, dexamethasone
No
Yes
3
66
F
Back pain, numbness, weakness Neck pain, numbness, weakness
C4
5
Anterior 141 decompression, cervical locking plate
325
Vincristine, doxorubicin dexamethasone
Yes
Yes
4
51
M
Back pain, numbness, weakness
L2
4
Dorsal decompression, posterior fixation
118
300
Bortezomib, dexamethasone thalidomide
No
Yes
5
49
M
Back pain, numbness, weakness
T3,4
5
Dorsal decompression, posterior fixation
245
720
Bortezomib, dexamethasone
No
Yes
6
67
F
Neck pain, numbness, weakness
C7
5
Anterior 157 decompression, cervical locking plate
384
Vincristine, doxorubicin dexamethasone
No
Yes
7
54
M
Back pain, numbness, weakness
T5
6
Dorsal decompression, posterior fixation
207
580
Bortezomib, dexamethasone thalidomide
Yes
Yes
8
69
M
Back pain, numbness, weakness
T10
5
Dorsal decompression, posterior fixation
172
416
Vincristine, doxorubicin dexamethasone
No
Yes
9
50
M
Back pain, numbness, weakness
L2
4
Dorsal decompression, posterior fixation
139
365
Bortezomib, dexamethasone
No
Yes
10
57
F
Back pain, numbness, weakness
L3
5
Dorsal decompression, posterior fixation
156
526
Bortezomib, dexamethasone
No
Yes
11
53
M
Back pain, numbness, weakness
T5
4
Dorsal decompression, posterior fixation
194
650
Bortezomib, dexamethasone
No
No
F female, M male, min minutes
Statistical analysis Continuous data were presented as the mean ± standard deviation, unless otherwise specified. Categorical variables were analyzed by the v2 test or Fisher’s exact test, and continuous variables were analyzed by the Student’s t test. P \ 0.05 was considered to be statistically significant. Statistical analyses were performed using SPSS software, version 13.0. RESULTS Preoperative and postoperative characteristics of all patients are shown in Table 1. Clinical follow-up was available for all patients, and the median follow-up time was 25.1 months (range 11–29 months). Partial tumor resection and stabilization of spine combined with chemotherapy were
successfully performed on all patients. The mean procedure time was 152.6 ± 30.4 min (range 118–245 min), and the mean blood loss was 396.4 ± 82.7 ml (range 300–720 ml). All patients completed the questionnaires before and after surgery and chemotherapy. The mean VAS score was 8.9 ± 1.1 before surgery and 3.4 ± 0.9 the first week postoperatively, which represented a statistically significant difference (P \ 0.05). At the last follow-up, the mean VAS score improved to 1.7 ± 0.8. In all patients, overall pain control rate was 89 %, with complete pain relief in 64 % and partial pain relief in 25 %. One patient was complicated by pleural effusion after surgery. The pleural effusion was successfully treated by percutaneous drainage. 2 months postoperatively, we observed the position of the titanium cage changed slightly in one case. This patient did not present clinical symptoms and did not require any further procedures. One patient
Treatment of Multiple Myeloma Spinal Cord Compression
developed severe thrombocytopenia and pulmonary infection during chemotherapy, and presented with the symptoms of epistaxis, hematuria, and cough. Temporary improvement of symptoms was obtained after blood platelet transfusion and anti-infection of the patient. Unfortunately, this patient died of pulmonary infection 11 months after surgery (9.1 %). Ten patients were alive at the last follow-up review. According to Frankel grade, nine of 11 cases were classified D grade and two cases were C grade before surgery. Neurological deficits progressed from D grade to C grade in one of two cases after admission. 6 months after surgery, there were 10 cases of E grade and one case of D grade. The mean muscular power recovered one to two grades. Spinal cord compressions were manifested on MRI in two patients (18.2 %) 3 months after surgery, and the extent of spinal cord compression was significantly less than that before surgery. However, with consideration of neurological function recovery of the two patients after surgery, chemotherapy was performed instead of re-surgery to treat the recurrence of spinal cord compression. The mean ODI score was 76.3 ± 14.6 preoperatively and 43.5 ± 0.9 at 3 months postoperatively. The last follow-up ODI score was 23.8 ± 7.5, which represented a statistically significant difference between preoperative stage and the last postoperative follow-up (P \ 0.05). The median pre-ODI values of 85 % significantly improved to 12 % at the last follow-up. Karnofsky score improved from 39 % before surgery to 62 % at 3 months after surgery and 75 % in ten survivors at the last follow-up. Comparison of their preoperative scores with the scores obtained 3 months postoperatively revealed that ten patients had improved, one patient stayed the same, and no patients declined. At the last follow-up, the scores of all ten surviving patients had improved from their preoperative levels.
DISCUSSION MM is a B cell neoplasm characterized by malignant plasma cells that arise in the bone marrow and produce osteolytic bone lesions.16 Progressive bone destruction is the mark of MM. The spine is the most affected skeletal organ, and single or multiple spinal lesions are due to bone destruction caused by MM.7 Pain, spinal instability, and spinal cord compression followed by spinal lesions affect quality of life and survival of patients suffering from this disease. Therefore, it is essential to treat spinal metastatic tumor derived from MM with an effective method to improve quality of life and prevent permanent disability.7,17 All possible efforts are aimed at maximizing quality of life.18 Furthermore, unlike other malignant spinal metastases, medical interventions must take into account
the relatively long period of survival in MM patients.19 However, the optimal treatment of metastatic spine lesions, especially associated with spinal cord compression, is not well-confirmed currently.20 Therefore, the aim of this study was to evaluate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression. Jin et al.8 reported a study that was conducted to investigate the role of single fraction radiosurgery for epidural spinal cord compression due to MM. Obvious radiographic changes of spinal cord compression were obtained in 81 % of patients at 3 months after radiosurgery and radiographic or neurological progression was not presented at the treated spine. Even obtaining relatively satisfactory results by means of radiosurgery, Du¨rr et al.9, 21 suggested urgent surgical treatment combined with additional medical method was an effective treatment for neurological function and quality of life in selected patients. Bisagni-Faure et al.22 reported 22 patients of spinal cord compression due to MM or plasmacytoma were performed with laminectomy, with or without local radiotherapy. Neurological function improved in 72 % of all cases, and the median of survival was 30 months. With the advancement of minimally invasive spine technology, percutaneous vertebroplasty (PV) was used to treat MM located in the spine.23,24 PV was an effective method for pain control resulting from spinal MM,23,24 but spinal cord compression and neurological deficits cannot be treated by PV. There are no guidelines for treatment of MM spinal cord compression until now, and individualized medical treatments for MM spinal cord compression should be rewarding. Therefore, partial tumor resection combined with chemotherapy for treatment of MM spinal cord compression was analyzed in this study. Three reasons were to be considered about this treatment method. The first reason was decompression of spinal cord for saving neurological function. The part of the tumor resulting in spinal cord compression must be resected, but the remaining part of the tumor within the involved vertebral body was not routinely resected for minor surgical trauma and lesser blood loss. This was different with other malignancies requiring total resection of the involved vertebral body. The second reason was stabilization of the spine for pain control. Pain relief can significantly improve the quality of life of survivors suffering from MM. The last reason was essential treatment for patients with MM by means of chemotherapy, which is the main treatment modality for MM.15 By using the treatment method of partial tumor resection combined with chemotherapy, there was a pain control rate of 89 %, a local recurrence rate of 18.2 %, and a survival rate of 90.9 % achieved within 29 months postoperatively for our patients. Different
J. Qian et al. TABLE 2 Summary of previously published literature of treating multiple myeloma spinal cord compression Author
Year Case Treatment method
Jin et al.8 Du¨rr et al.9
2009 24
Radiosurgery
2002 27
Surgery
Chataigner et al.21
1998 18
Bisagni-Faure et al.22
Pain control rate
Average survival (month)
Complication and number
Recurrence
86.4 %
–
Tracheoesophageal fistula: 1
1
96.2 %
49.7
Deep vein thrombosis: 1; hemothorax: 1; 3 paraplegia: 1; wound infection: 1; device-related complication: 1
Surgery ± radiotherapy/ 50.0 % immunotherapy
36.2
Local infections: 2; implant mobilization: 1
1
1991 22
Surgery ± radiotherapy 72.0 %
30
Wound infection: 1
2
Anselmetti et al.23
2012 106
Percutaneous vertebroplasty
95.3 %
–
Disseminated intravascular coagulopathy: 1; bacterial infection: 1
16
Mont’Alverne et al.24
2009 4
Percutaneous vertebroplasty
100 %
–
Cement leakage: 3; spinal instability: 1
–
chemotherapy regimens were selected for our patients according to the age and the level of serum creatinine of all patients.12,13 Furthermore, there was no difference in clinical outcome, including pain control and recurrence of spinal cord compression between different patients who underwent different chemotherapy regimens. To the best of our knowledge, this is the first report of clinical outcome of partial tumor resection combined with chemotherapy for MM spinal cord compression. Although relatively good clinical outcomes were obtained by the treatment of partial tumor resection combined with chemotherapy, we believed that some limitations were to be presented. Because of the low incidence of MM, we did not have a control group in this paper, and there was not a comparator group (e.g., surgery alone or chemotherapy alone, or surgery combined with radiation that can be used). These may lead to biased results. Therefore, the clinical outcome of partial tumor resection combined with chemotherapy in this study was compared with the outcome presented in previous papers about the treatment of MM spinal cord compression (Table 2). Furthermore, the follow-up time was relatively short, and local tumor recurrence and death of patients may be missed. Based on this present study, it is suggested that partial tumor resection has the advantage of minor surgical trauma, fewer complications, and effective pain control. The most important is that clinical outcomes have not been weakened, even when the tumor is partially resected. This surgical method, combined with chemotherapy, seems to be an effective treatment for patients with MM spinal cord compression. Total resection of the tumor is not necessary for MM of the spine. ACKNOWLEDGMENT We thank Jue-hua Jing and Hui-lin Yang for their technical surgical support.
DISCLOSURE Jun Qian, Juehua Jing, Dasheng Tian, and Huilin Yang have no conflicts of interest or financial ties to disclose.
REFERENCES 1. Angtuaco EJ, Fassas AB, Walker R, Sethi R, Barlogie B. Multiple myeloma: clinical review and diagnostic imaging. Radiology. 2004;231:11–23. 2. Okacha N, Chrif E, Brahim E, et al. Extraosseous epidural multiple myeloma presenting with thoracic spine compression. Joint Bone Spine. 2008;75:70–2. 3. Braggio E. Incidence and prognostic value of recurrent chromosomal abnormalities in elderly patients with multiple myeloma. Future Oncol. 2013;9:1805–8. 4. Dispenzieri A, Kyle RA. Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol. 2005;18:673–88. 5. Watanabe Y, Endou A, Ooi S, Matsushima E, Shimisu Y, Nakashima K. Extraosseous epidural IgD myeloma presenting with compression myeopathy. Psychiatry Clin Neurosci. 2000;54:665–7. 6. Durman DC. Myeloma of the spine. Ann Surg. 1928; 88:975–84. 7. Latif T, Hussein MA. Advances in multiple myeloma and spine disease. Clin Lymphoma Myeloma. 2005;6:228–33. 8. Jin R, Rock J, Jin JY, et al. Single fraction spine radiosurgery for myeloma epidural spinal cord compression. J Exp Ther Oncol. 2009;8:35–41. 9. Du¨rr HR, Wegener B, Kro¨del A, Mu¨ller PE, Jansson V, Refior HJ. Multiple myeloma: surgery of the spine: retrospective analysis of 27 patients. Spine.2002;27:320–4. 10. Huang W, Cao D, Ma J, et al. Solitary plasmacytoma of cervical spine: treatment and prognosis in patients with neurological lesions and spinal instability. Spine. 2010;35:E278–84. 11. Tomita K, Kawahara N, Baba H, Tsuchiya H, Nagata S, Toribatake Y. Total en bloc spondylectomy for solitary spinal metastases. Int Orthop. 1994;18:291–8. 12. Kouroukis CT, Baldassarre FG, Haynes AE, Imrie K, Reece DE, Cheung MC. Bortezomib in multiple myeloma: a practice guideline. Clin Oncol (R Coll Radiol). 2013;26(2):110–9. 13. Anderson H, Scarffe JH, Ranson M, et al. VAD chemotherapy as remission induction for multiple myeloma. Br J Cancer. 1995;71:326–30.
Treatment of Multiple Myeloma Spinal Cord Compression 14. Frankel HL. Ascending cord lesion in the early stages following spinal injury. Paraplegia. 1969;7:111–8. 15. Karnofsky DA, Abelmann WA, Craver LF, et al. The use of nitrogen mustard in the palliative treatment of carcinoma. Cancer. 1948;1:634–9. 16. Joshua D, Brown R, Ho PJ. Multiple myeloma: challenges and opportunities. Methods Mol Med. 2005;113:1–4. 17. Snowden JA, Ahmedzai SH, Ashcroft J, D’Sa S, Littlewood T, Low E. Guidelines for supportive care in multiple myeloma 2011. Br J Haematol. 2011;154:76–103. 18. Smith ML, Newland AC. Treatment of myeloma. QJM. 1999;92:11–4. 19. Wegener B, Mu¨ller PE, Jansson V, Kro¨del A, Heinert G, Du¨rr HR. Cervical spine metastasis of multiple myeloma: a case report with 16 years of follow-up. Spine (Phila Pa 1976). 2004;29: E368–72. 20. Kim JM, Losina E, Bono CM, et al. Clinical outcome of metastatic spinal cord compression treated with surgical
21.
22.
23.
24.
excision ± radiation versus radiation therapy alone: a systematic review of literature. Spine (Phila Pa 1976). 2012;37:78–84. Chataigner H, Onimus M, Polette A. Surgical treatment of myeloma localized in the spine. Rev Chir Orthop Reparatrice Appar Mot. 1998;84:311–8. Bisagni-Faure A, Ravaud P, Amor B, Menke`s CJ. Myeloma and epidural invasiveness. Clinical and therapeutic aspects (a study of 22 cases). Rev Rhum Mal Osteoartic. 1991;58:501–6. Anselmetti GC, Manca A, Montemurro F, et al. Percutaneous vertebroplasty in multiple myeloma: prospective long-term follow-up in 106 consecutive patients. Cardiovasc Intervent Radiol. 2012;35:139–45. Mont’Alverne F, Valle´e JN, Guillevin R, et al. Percutaneous vertebroplasty for multiple myeloma of the cervical spine. Neuroradiology. 2009;51:237–42.
ORIGINAL ARTICLE – NEURO-ONCOLOGY
Partial Tumor Resection Combined with Chemotherapy for Multiple Myeloma Spinal Cord Compression Jun Qian, MD1, Juehua Jing, MD1, Dasheng Tian, MD1, and Huilin Yang, MD2 1
Department of Orthopaedics, The Second Hospital of An Hui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China
ABSTRACT Background. Some controversies about the optimal therapy for multiple myeloma (MM) spinal cord compression are still presented. This study was conducted to investigate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression. Methods. Eleven patients were diagnosed with MM spinal cord compression. Radiological examinations manifested 12 spinal lesions on 11 patients. All patients were treated with partial tumor resection with adjuvant chemotherapy. The mean procedure time, the mean blood loss, visual analog scale score, Oswestry Disability Index (ODI) score, neurological status, complication, recurrence, and quality of life were evaluated. Results. Eleven patients were followed up with a mean of 25.1 months. The mean procedure time was 152.6 ± 30.4 min, and the mean blood loss was 396.4 ± 82.7 ml. Overall pain control rate was 89 %, with complete pain relief in 64 %, and partial pain relief in 25 %. The median pre-ODI values of 85 % significantly improved to 12 % at the last follow-up. Neurological improvement of one to two grades was observed 6 months postoperatively. Complications included pleural effusion, titanium cage loose, and thrombocytopenia in three patients each. Local recurrence was 18.2 %. One patient died of pulmonary infection. Quality of life improved from 39 % before surgery to 81 % in ten survivors at the last follow-up. Conclusions. Partial tumor resection combined with chemotherapy seems to be an effective treatment for MM spinal cord compression owing to the minor surgical trauma, fewer
complications, and effective pain control. Total resection of the tumor is not necessary for MM of the spine.
Ó Society of Surgical Oncology 2014
MATERIALS AND METHODS
INTRODUCTION Multiple myeloma (MM) is a hematological malignancy characterized by accumulation of monoclonal plasma cells. It accounts for approximately 1 % of all cancers and represents about 10 % of all hematological malignancies.1 It affects the bone marrow and presents as multiple osteolytic lesions with the most common localization being the spine.2,3 Pathological fracture of the vertebral body resulting in spinal cord compression is a common complication of this disorder.4 Spinal cord compression accounts for approximately 5 % of patients with MM.5 The first outstanding symptom is neck pain or back pain as MM attacks the spine, and the pain may be worse with movement.6 The spinal cord compression due to pathological collapse of the vertebral body by MM presents a progressive neurological deficit. This is the next most characteristic clinical sign of spinal MM.6 Traditional treatments of osteolytic vertebral collapse for pain control included bed rest, bracing, and analgesics.7 Surgical resection and radiation therapy were the main treatments for MM spinal cord compressions described in previous papers.7–10 Less experience with surgical treatment combined with chemotherapy for MM spinal cord compression was discussed. The aim of this study was to investigate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression.
First Received: 11 January 2014 J. Jing, MD e-mail: [email protected]
We have obtained the approval from the ethics committee of the second hospital of An Hui Medical
J. Qian et al.
University. All patients have provided written informed consent to participate in this study, and the ethics committee of our hospital has approved this procedure. Furthermore, our study meets the guidelines of the responsible governmental agency. Patients Eleven patients underwent partial tumor resection combined with chemotherapy for MM spinal cord compression between October 2008 and July 2012. There were women and eight men with a mean age of 60.3 years (range 47– 69 years). All patients complained of severe neck pain or back pain, numbness, and weakness of lower extremities between 3 and 17 months (average 5.8 months). Neck pain or back pain and neurological deficits gradually worsened during this time. Physical examinations showed neurological deficits resulted from spinal cord compression. Standard radiological examinations including X-ray, magnetic resonance imaging (MRI), and three-dimensional computed tomography (CT) were performed to prove the spinal lesion. X-rays showed 11 vertebral body fractures of whole spine on all patients, but 12 vertebral destructions and spinal cord compression at the same level were illustrated by MRI. Osteolytic lesions were located in the cervical spine in two patients, the thoracic spine in five patients, and the lumbar spine in four patients. Heterogeneous hyposignal in T1weighted spin-echo sequence and hypersignal in T2weighted spin-echo sequence were shown within the osteolytic lesion. Three-dimensional CT showed osteolytic destruction, expansive growth, and soft tissue mass. Emission computed tomography (ECT) revealed multiple bone involvements, except spinal lesions. Based on MRI and CT, it was strongly suggested that the spinal osteolytic lesion was caused by MM. According to the grade system developed by Tomita et al.11 three patients were classified as grade 4, six patients were grade 5, and 2 patients were grade 6. Laboratory studies including serum protein electrophoresis showed a Bence-Jones protein and a monoclonal hypergammaglobulinemia were positive in 11 patients. Bone marrow aspiration and biopsy confirmed MM (20 % abnormal plasma cells) in nine patients. Ten patients were diagnosed with MM and one patient was suspicious of MM by laboratory tests and bone marrow biopsy before treatment. Surgical procedures The surgical strategy consisted of decompression of the spinal cord and stabilization of the spine for pain control and neurological function recovery. Complete tumor
FIG. 1 A 67-year-old female patient presenting with a history of neck pain, numbness, and weakness of the lower extremities for 7 months was diagnosed as multiple myeloma spinal cord compression. We performed anterior decompression, corpectomy of the involved vertebral, removal of soft tissue mass that was creating spinal cord compression, iliac strut graft, and a cervical spine locking plate. a and b are T1 and T2 magnetic resonance images of the cervical spine before surgery, respectively. The vertebral body of C7 is destroyed and the spinal cord is compressed at the same level. c is ECT picture before surgery. d is an X-ray of the cervical spine after surgery
resection is not the primary goal of the surgery. We performed partial tumor resection and spinal fixation on all patients. Reconstructions were done with iliac bone graft and a cervical spine locking plate in two patients, iliac bone graft with titanium cage and posterior instrumentation in four patients, and iliac bone graft and posterior instrumentation in five patients. Anterior decompression, corpectomy of the involved vertebral, removal of soft tissue mass creating spinal cord compression, iliac strut graft, and a cervical spine locking plate were performed in the cervical osteolytic lesions (Fig. 1). We did not resect the outer edge within the tumor vertebral body for minor surgical trauma and less blood loss. Dorsal decompression, transpedicular partial tumor resection, iliac strut graft, titanium cage and pedicle screws were carried out in thoracic and lumbar lesions (Figs. 2, 3). The anterior edge and contralateral of decompression within the tumor vertebral body were not routinely resected like other malignancies.
Treatment of Multiple Myeloma Spinal Cord Compression
FIG. 2 A 49-year-old male patient presenting with a history of back pain, numbness, and weakness of the lower extremities for 4 months was diagnosed as multiple myeloma spinal cord compression. We performed dorsal decompression, transpedicular partial tumor resection, iliac strut graft, with a titanium cage and pedicle screws. a and b are T1 and T2 magnetic resonance images of the thoracic spine before surgery, respectively. The vertebral body of T4 and lamina of T3,4 are destroyed and the spinal cord is compressed at the level of T4. c is ECT picture before surgery. d is an X-ray of the thoracic spine after surgery
FIG. 3 A 47-year-old male patient presenting with a history of back pain, numbness, and weakness of the lower extremities for 11 months was diagnosed as multiple myeloma spinal cord compression. We performed dorsal decompression, transpedicular partial tumor resection, iliac strut graft, and used pedicle screws. a and b are T1 and T2 magnetic resonance images of thoracic spine before surgery, respectively. The vertebral body of L5 is destroyed and the spinal cord is compressed at the level of L5. c is a three-dimensional computed tomography (CT) picture before surgery. d is an X-ray of the lumbar spine after surgery
Postoperative care
together with oral dexamethasone (40 mg daily) for 4 days. This VAD chemotherapy was repeated every 21 days for four cycles.
All patients received alendronate therapy at an oral dose of 70 mg/week. An external spine brace was also used for the purpose of early ambulation.
Effectiveness assessment
Chemotherapy All patients were treated with chemotherapy 3 weeks postoperatively. Eight patients had undergone chemotherapy including bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of each 21-day cycle for four cycles, and together with oral dexamethasone (40 mg daily) on days 1–4, 9–12, and 17–20 for four cycles.12 Thalidomide was used in three of the eight patients. The starting amount of thalidomide was 100 mg/day, according to the patient’s condition, which was gradually increased to 200 mg/day. The other three patients were carried out by vincristine, doxorubicin and dexamethasone (VAD) chemotherapy.13 Vincristine (total dose 1.6 mg) with doxorubicin (36 mg/m2) over 4 days,
The following parameters were investigated to assess the efficacy: (1) the mean procedure time, (2) the mean blood loss, (3) VAS score, (4) ODI score, (5) complications, (6) recurrence, (7) neurological status,14 and (8) quality of life.15 Follow-up The follow-up methods consisted of questionnaires or personal contact with patients (either by phone or clinical investigation). Laboratory studies and radiological examinations, including MRI, were done to evaluate the patient’s condition, recurrence of spinal cord compression, stability of instrumentations, and bone graft fusion during the follow-up.
J. Qian et al. TABLE 1 Preoperative and postoperative characteristics of all patients Case Age Sex Symptoms (years)
Location Tomita Surgical treatment grade
Procedure Blood Chemotherapy time loss (min) (ml)
Recurrence Alive
1
53
M
Back pain, numbness, weakness
T9
6
Dorsal decompression, posterior fixation
215
631
Bortezomib, dexamethasone thalidomide
No
Yes
2
47
M
L5
5
Dorsal decompression, posterior fixation
186
359
Bortezomib, dexamethasone
No
Yes
3
66
F
Back pain, numbness, weakness Neck pain, numbness, weakness
C4
5
Anterior 141 decompression, cervical locking plate
325
Vincristine, doxorubicin dexamethasone
Yes
Yes
4
51
M
Back pain, numbness, weakness
L2
4
Dorsal decompression, posterior fixation
118
300
Bortezomib, dexamethasone thalidomide
No
Yes
5
49
M
Back pain, numbness, weakness
T3,4
5
Dorsal decompression, posterior fixation
245
720
Bortezomib, dexamethasone
No
Yes
6
67
F
Neck pain, numbness, weakness
C7
5
Anterior 157 decompression, cervical locking plate
384
Vincristine, doxorubicin dexamethasone
No
Yes
7
54
M
Back pain, numbness, weakness
T5
6
Dorsal decompression, posterior fixation
207
580
Bortezomib, dexamethasone thalidomide
Yes
Yes
8
69
M
Back pain, numbness, weakness
T10
5
Dorsal decompression, posterior fixation
172
416
Vincristine, doxorubicin dexamethasone
No
Yes
9
50
M
Back pain, numbness, weakness
L2
4
Dorsal decompression, posterior fixation
139
365
Bortezomib, dexamethasone
No
Yes
10
57
F
Back pain, numbness, weakness
L3
5
Dorsal decompression, posterior fixation
156
526
Bortezomib, dexamethasone
No
Yes
11
53
M
Back pain, numbness, weakness
T5
4
Dorsal decompression, posterior fixation
194
650
Bortezomib, dexamethasone
No
No
F female, M male, min minutes
Statistical analysis Continuous data were presented as the mean ± standard deviation, unless otherwise specified. Categorical variables were analyzed by the v2 test or Fisher’s exact test, and continuous variables were analyzed by the Student’s t test. P \ 0.05 was considered to be statistically significant. Statistical analyses were performed using SPSS software, version 13.0. RESULTS Preoperative and postoperative characteristics of all patients are shown in Table 1. Clinical follow-up was available for all patients, and the median follow-up time was 25.1 months (range 11–29 months). Partial tumor resection and stabilization of spine combined with chemotherapy were
successfully performed on all patients. The mean procedure time was 152.6 ± 30.4 min (range 118–245 min), and the mean blood loss was 396.4 ± 82.7 ml (range 300–720 ml). All patients completed the questionnaires before and after surgery and chemotherapy. The mean VAS score was 8.9 ± 1.1 before surgery and 3.4 ± 0.9 the first week postoperatively, which represented a statistically significant difference (P \ 0.05). At the last follow-up, the mean VAS score improved to 1.7 ± 0.8. In all patients, overall pain control rate was 89 %, with complete pain relief in 64 % and partial pain relief in 25 %. One patient was complicated by pleural effusion after surgery. The pleural effusion was successfully treated by percutaneous drainage. 2 months postoperatively, we observed the position of the titanium cage changed slightly in one case. This patient did not present clinical symptoms and did not require any further procedures. One patient
Treatment of Multiple Myeloma Spinal Cord Compression
developed severe thrombocytopenia and pulmonary infection during chemotherapy, and presented with the symptoms of epistaxis, hematuria, and cough. Temporary improvement of symptoms was obtained after blood platelet transfusion and anti-infection of the patient. Unfortunately, this patient died of pulmonary infection 11 months after surgery (9.1 %). Ten patients were alive at the last follow-up review. According to Frankel grade, nine of 11 cases were classified D grade and two cases were C grade before surgery. Neurological deficits progressed from D grade to C grade in one of two cases after admission. 6 months after surgery, there were 10 cases of E grade and one case of D grade. The mean muscular power recovered one to two grades. Spinal cord compressions were manifested on MRI in two patients (18.2 %) 3 months after surgery, and the extent of spinal cord compression was significantly less than that before surgery. However, with consideration of neurological function recovery of the two patients after surgery, chemotherapy was performed instead of re-surgery to treat the recurrence of spinal cord compression. The mean ODI score was 76.3 ± 14.6 preoperatively and 43.5 ± 0.9 at 3 months postoperatively. The last follow-up ODI score was 23.8 ± 7.5, which represented a statistically significant difference between preoperative stage and the last postoperative follow-up (P \ 0.05). The median pre-ODI values of 85 % significantly improved to 12 % at the last follow-up. Karnofsky score improved from 39 % before surgery to 62 % at 3 months after surgery and 75 % in ten survivors at the last follow-up. Comparison of their preoperative scores with the scores obtained 3 months postoperatively revealed that ten patients had improved, one patient stayed the same, and no patients declined. At the last follow-up, the scores of all ten surviving patients had improved from their preoperative levels.
DISCUSSION MM is a B cell neoplasm characterized by malignant plasma cells that arise in the bone marrow and produce osteolytic bone lesions.16 Progressive bone destruction is the mark of MM. The spine is the most affected skeletal organ, and single or multiple spinal lesions are due to bone destruction caused by MM.7 Pain, spinal instability, and spinal cord compression followed by spinal lesions affect quality of life and survival of patients suffering from this disease. Therefore, it is essential to treat spinal metastatic tumor derived from MM with an effective method to improve quality of life and prevent permanent disability.7,17 All possible efforts are aimed at maximizing quality of life.18 Furthermore, unlike other malignant spinal metastases, medical interventions must take into account
the relatively long period of survival in MM patients.19 However, the optimal treatment of metastatic spine lesions, especially associated with spinal cord compression, is not well-confirmed currently.20 Therefore, the aim of this study was to evaluate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression. Jin et al.8 reported a study that was conducted to investigate the role of single fraction radiosurgery for epidural spinal cord compression due to MM. Obvious radiographic changes of spinal cord compression were obtained in 81 % of patients at 3 months after radiosurgery and radiographic or neurological progression was not presented at the treated spine. Even obtaining relatively satisfactory results by means of radiosurgery, Du¨rr et al.9, 21 suggested urgent surgical treatment combined with additional medical method was an effective treatment for neurological function and quality of life in selected patients. Bisagni-Faure et al.22 reported 22 patients of spinal cord compression due to MM or plasmacytoma were performed with laminectomy, with or without local radiotherapy. Neurological function improved in 72 % of all cases, and the median of survival was 30 months. With the advancement of minimally invasive spine technology, percutaneous vertebroplasty (PV) was used to treat MM located in the spine.23,24 PV was an effective method for pain control resulting from spinal MM,23,24 but spinal cord compression and neurological deficits cannot be treated by PV. There are no guidelines for treatment of MM spinal cord compression until now, and individualized medical treatments for MM spinal cord compression should be rewarding. Therefore, partial tumor resection combined with chemotherapy for treatment of MM spinal cord compression was analyzed in this study. Three reasons were to be considered about this treatment method. The first reason was decompression of spinal cord for saving neurological function. The part of the tumor resulting in spinal cord compression must be resected, but the remaining part of the tumor within the involved vertebral body was not routinely resected for minor surgical trauma and lesser blood loss. This was different with other malignancies requiring total resection of the involved vertebral body. The second reason was stabilization of the spine for pain control. Pain relief can significantly improve the quality of life of survivors suffering from MM. The last reason was essential treatment for patients with MM by means of chemotherapy, which is the main treatment modality for MM.15 By using the treatment method of partial tumor resection combined with chemotherapy, there was a pain control rate of 89 %, a local recurrence rate of 18.2 %, and a survival rate of 90.9 % achieved within 29 months postoperatively for our patients. Different
J. Qian et al. TABLE 2 Summary of previously published literature of treating multiple myeloma spinal cord compression Author
Year Case Treatment method
Jin et al.8 Du¨rr et al.9
2009 24
Radiosurgery
2002 27
Surgery
Chataigner et al.21
1998 18
Bisagni-Faure et al.22
Pain control rate
Average survival (month)
Complication and number
Recurrence
86.4 %
–
Tracheoesophageal fistula: 1
1
96.2 %
49.7
Deep vein thrombosis: 1; hemothorax: 1; 3 paraplegia: 1; wound infection: 1; device-related complication: 1
Surgery ± radiotherapy/ 50.0 % immunotherapy
36.2
Local infections: 2; implant mobilization: 1
1
1991 22
Surgery ± radiotherapy 72.0 %
30
Wound infection: 1
2
Anselmetti et al.23
2012 106
Percutaneous vertebroplasty
95.3 %
–
Disseminated intravascular coagulopathy: 1; bacterial infection: 1
16
Mont’Alverne et al.24
2009 4
Percutaneous vertebroplasty
100 %
–
Cement leakage: 3; spinal instability: 1
–
chemotherapy regimens were selected for our patients according to the age and the level of serum creatinine of all patients.12,13 Furthermore, there was no difference in clinical outcome, including pain control and recurrence of spinal cord compression between different patients who underwent different chemotherapy regimens. To the best of our knowledge, this is the first report of clinical outcome of partial tumor resection combined with chemotherapy for MM spinal cord compression. Although relatively good clinical outcomes were obtained by the treatment of partial tumor resection combined with chemotherapy, we believed that some limitations were to be presented. Because of the low incidence of MM, we did not have a control group in this paper, and there was not a comparator group (e.g., surgery alone or chemotherapy alone, or surgery combined with radiation that can be used). These may lead to biased results. Therefore, the clinical outcome of partial tumor resection combined with chemotherapy in this study was compared with the outcome presented in previous papers about the treatment of MM spinal cord compression (Table 2). Furthermore, the follow-up time was relatively short, and local tumor recurrence and death of patients may be missed. Based on this present study, it is suggested that partial tumor resection has the advantage of minor surgical trauma, fewer complications, and effective pain control. The most important is that clinical outcomes have not been weakened, even when the tumor is partially resected. This surgical method, combined with chemotherapy, seems to be an effective treatment for patients with MM spinal cord compression. Total resection of the tumor is not necessary for MM of the spine. ACKNOWLEDGMENT We thank Jue-hua Jing and Hui-lin Yang for their technical surgical support.
DISCLOSURE Jun Qian, Juehua Jing, Dasheng Tian, and Huilin Yang have no conflicts of interest or financial ties to disclose.
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