Leiomyosarcoma is a malignant soft tissue sarcoma. Outcomes after surgery for spinal metastatic leiomyosarcoma. Clinical article

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1 J Neurosurg Spine 17: , 2012 Outcomes after surgery for spinal metastatic leiomyosarcoma Clinical article John E. Ziewacz, M.D., M.P.H., Darryl Lau, B.A., Frank La Marca, M.D., and Paul Park, M.D. Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan Object. Leiomyosarcoma is a smooth-muscle sarcoma that rarely metastasizes to the spine. Its clinical course is variable, although patients with metastatic leiomyosarcoma can experience prolonged survival as compared with patients with more aggressive metastatic tumors. The authors report their single-institution experience in the surgical treatment of patients with leiomyosarcoma metastatic to the spine. Methods. A retrospective review of the electronic medical records was performed to obtain details on clinical management and outcomes for patients who had undergone surgical intervention for metastatic leiomyosarcoma of the spine. The few articles available in the current literature on this topic were also analyzed. Results. Eight patients with metastatic leiomyosarcoma of the spine underwent surgical management between 2005 and Six patients (75%) had improvement in their Nurick grade. Patients who had presented with pain as a primary symptom experienced significant relief. Five patients (63%) had lesion recurrence, and 4 underwent repeat surgery at a mean of 10.2 months after their initial surgery. The mean duration of survival was 11.7 months (range months). Conclusions. Leiomyosarcoma rarely metastasizes to the spine. However, surgical intervention can relieve pain and improve neurological function. Given the potential for prolonged survival, aggressive management should be considered in well-selected patients. ( Key Words spine metastasis leiomyosarcoma surgery cancer oncology Leiomyosarcoma is a malignant soft tissue sarcoma originating from smooth-muscle cells and typically arises in the uterus, retroperitoneal space, abdominal viscera, or soft tissues of the extremities, with an estimated overall incidence of 0.7 case per 100,000 persons per year. 4 Spinal metastasis is rare and typically represents a late manifestation of the disease. 5,9 Given reports of prolonged survival following the surgical management of both metastatic and primary spinal leiomyosarcomas, aggressive resection has been advocated when feasible. 5,10,16,18 The largest surgical series of metastatic spinal leiomyosarcoma included 5 patients. 5 In the present article, we report on a single-institution series of 8 surgically managed patients with metastatic spinal leiomyosarcoma and review the current literature on this topic. Methods After obtaining approval from the University of Michigan institutional review board, we retrospectively Abbreviation used in this paper: VAS = visual analog scale. reviewed the electronic medical records at our institution to identify all patients who had undergone surgical management of metastatic leiomyosarcoma of the spine. In each case, pathological examination confirmed that the diagnosis was consistent with metastatic leiomyosarcoma. In addition, the primary site of the leiomyosarcoma was identified in all cases. Presenting symptoms, demographic information, surgical procedure, and outcome for each patient were reviewed. Surgery was recommended for each patient after discussions with oncology and radiation oncology personnel. Specific criteria for surgery included a life expectancy of at least 3 months, neurological deficit, refractory pain, radiographic instability, and/ or tumor progression despite chemotherapy and radiation. Most patients received chemotherapy and radiotherapy as an adjunct to surgery. Postoperative improvements were assessed using individual motor strength testing, the Nurick scale for myelopathy, 11 and the VAS for pain. On the VAS scale, 0 was considered no pain, and 10 was considered the worst pain possible. Recurrence of the patient s metastatic lesion and the need for repeat surgery were also assessed and documented. Duration of survival after surgery was recorded as well. 432 J Neurosurg: Spine / Volume 17 / November 2012

2 Outcomes after surgery for spinal metastatic leiomyosarcoma Results Eight patients were identified for the period from 2005 to Table 1 provides demographic information, clinical details, and specific outcomes for these patients. The patient in Case 7 had previously undergone thoracic laminectomy for resection of a metastasis, and his initial presentation at our institution was for a recurrence. The mean age at the time of surgery was 50.9 years (range years). Five (62.5%) of the 8 patients were women. The primary leiomyosarcoma site was the uterus in 4 of these women and the chest wall in 1. The 3 men in the series had primary leiomyosarcoma originating from the thigh, retroperitoneal space, or knee. Three patients (38%) were unable to ambulate prior to surgery. Metastases occurred in the thoracic spine in 6 patients (75%) and in the lumbar spine in 2 (25%). The specific surgical procedure performed varied for each patient, ranging from aggressive procedures, such as vertebrectomy with anterior and posterior instrumentation, to laminectomy for resection of epidural tumor (Figs. 1 and 2). In all cases, tumor resection was intralesional. While the goal was maximal tumor resection, residual disease was likely, given the use of the intralesional approach. Allograft bone was used in instrumented cases to promote fusion. The average estimated blood loss was 650 ml. No complications were noted. In terms of postoperative outcomes, 6 patients had improvement in their Nurick grades. Among the 3 patients unable to ambulate preoperatively, all could do so postoperatively with improvement to Nurick Grade 3. In the patients who had presented with pain as a primary symptom, all had significant relief with at least a 2-point improvement in VAS score. Five patients (63%) had lesion recurrence, and 4 underwent repeat surgery for the metastatic lesion at a mean of 10.2 months (range months). Increased pain and/or myelopathy were present at the time of recurrence (Table 2). The majority of patients who underwent repeat surgery had pain relief and/ or improved myelopathy. The patient in Case 3 presented with worsening pain 7 months after her initial surgery and was found to have a recurrence (Table 1). After extensive discussion, she elected not to pursue further surgery until she presented with paraplegia 9 months after her initial surgery. Unfortunately, she had no improvement after the repeat surgery. The patient in Case 4 presented with worsening myelopathy and had improvement after repeat surgery. Six months later, however, she had another recurrence with associated myelopathy. Despite further surgery, her condition did not significantly improve. Although fusion was not assessed with postoperative CT studies, no evidence of hardware failure was noted on postoperative radiography. As of this writing, 7 patients have died. The mean survival was 11.7 months (range months) from the time of the first surgery. Discussion Leiomyosarcoma is a soft tissue sarcoma of mesenchymal derivation with a typically poor prognosis. 15 A national prognostic survey from Norway estimated J Neurosurg: Spine / Volume 17 / November 2012 overall 5-year survival for uterine leiomyosarcoma to be 15% 25%. 1 All patients with extrauterine spread in that same study had died at 5 years. A study of nonvisceral leiomyosarcoma demonstrated a 10-year survival of 49% overall, although this rate included cutaneous leiomyosarcomas, which are thought to be more benign. 15,17 In this context, surgery for primary or metastatic leiomyosarcomas of the spine, which are histologically indistinct from one another, has been considered solely for palliation. 10 However, the clinical course of leiomyosarcoma can be variable and depends on tumor location, histological grade, disease stage, and clinical status of the patient. Prolonged survival (usually more than 1 year for metastatic cancer) in those with primary or metastatic spinal lesions has been observed. 1,5,15,17 This realization, as well as recent surgical advances, has prompted some authors to advocate more aggressive approaches. 5,10,18 Spinal leiomyosarcoma, whether primary or metastatic, is rare. Furthermore, some question whether many of the lesions that are considered primary leiomyosarcoma of the spine are actually metastatic, especially given the documented underdiagnosis of leiomyosarcoma of the uterus in specimens previously diagnosed as benign leiomyoma. 5,6 Note that primary spinal leiomyosarcoma does appear to exist in the absence of uterine or other primary disease. 8,10,12,13,16 The literature particular to surgically treated metastatic spinal leiomyosarcoma consists of case reports and 1 case series of 5 patients. 2,3,5,7,9,14,16,18 The surgical case series by Elhammady et al. 5 documents 5 patients, all women with uterine primaries who presented with thoracic or lumbar metastases. These patients ranged in age from 36 to 47 years, and only one presented with weakness while the others presented with pain alone or pain and sensory deficit as the only neurological symptoms. They all underwent varied surgical approaches ranging from laminectomy and fusion to transpedicular vertebrectomy or corpectomy and fusion. In concert with these findings, metastases among our series of 8 patients demonstrated a predilection for the thoracic or lumbar spine, with 6 patients harboring thoracic metastases and the remainder harboring lumbar metastases. The mean age of 50.9 years in our study is comparable to that in the Elhammady et al. 5 study and highlights the relatively young age of those affected by metastatic leiomyosarcoma. We also used a variety of surgical approaches ranging from laminectomy to laminectomy and fusion as well as posterolateral vertebrectomy and fusion, depending on the location of the mass, extent of disease, and goals of therapy. In contrast to that previous case series, in which 2 patients died 13 and 14 years after diagnosis and 3 patients remained alive at 36 months, 42 months, and 8 years after diagnosis, our series demonstrated a shorter survival time, that is, a mean survival of 11.7 months after surgery in 7 patients (88%), and 1 patient alive at 10 months after surgery. 5 This difference in survival duration could be attributed to the fact that patients in our series may have had worse disease. Three of our patients were nonambulatory at baseline, whereas patients from the Elhammady et al. 5 study presented with pain only, except in 1 case in which weakness was present. Importantly, all of the patients with surgically treated 433

3 J. E. Ziewacz et al. TABLE 1: Characteristics, clinical details, and outcomes for patients undergoing resection of spinal metastatic leiomyosarcoma* Case No. Sex Age (yrs) Presentation Primary Tumor Location Spinal Level Chemotherapy/ Radiotherapy? Surgery Outcome 1 M 25 back pain w/ radiation to ant chest; diminished sensation in lt leg from hip down thigh T-5 yes/yes T4 5 laminectomy; T-5 vertebrectomy; interbody cage placement; T3 7 pst fusion 2 F 61 nonradiating low-back pain chest wall L-1 yes/yes T12 L2 laminectomy; T12 L2 pst fusion 3 F 35 radiating pain in rt arm, armpit, & back 4 F 57 thoracic back pain; burning pain & loss of function in lt hand; autonomic dysfunction; unable to ambulate 5 F 57 tingling in rt foot; radicular pain in buttocks & thigh 6 F 51 bilat lower extremity weakness, tingling, & numbness 7 M 55 worsening back pain; unable to ambulate 8 M 66 lower extremity weakness; unable to ambulate; loss of bladder control uterus T1 3 yes/yes T-2 hemilaminectomy; T-2 transpedicular tumor resection; C6 T4 pst fusion uterus T-1 yes/yes C7 T2 laminectomy; bilat transpedicular partial corpectomy of T-1; C5 T3 pst fusion improved Nurick grade (3 to 2) & strength; improved VAS score (7 to 0) for back pain at 4-mo FU improved Nurick grade (1 to 0) & improved VAS score (4 to 0) for back pain improved VAS score (7 to 5) at 3-mo FU improved Nurick grade (5 to 3); improved VAS score (8 to 4) at 9-mo FU uterus L4 S1 yes/yes L4 S1 hemilaminectomy improved VAS score (6 to 1) for back & leg pain at 3-mo FU uterus T2 4 no/no T2 4 laminectomy; T1 5 pst fusion retroperitoneal mass T10 12 yes/yes redo T10 12 laminectomy & pst fusion improved Nurick grade (3 to 2) score & strength improved Nurick grade (5 to 3) & strength; improved VAS score (5 to 3) for back pain at time of recurrence lt knee T-4 yes/no T1 4 laminectomy improved Nurick grade (5 to 3) & strength * ant = anterior; FU = follow-up; pst = posterior. Recurrence (mo)/ Repeat Surgery? Survival (mos) yes (8.1)/yes 15.1 no alive at 10 yes (7)/yes, at 9 mos 11.5 yes (9.9)/yes 20.3 yes (13.8)/yes 23.0 no 3.3 yes (2.2)/no 5.7 no J Neurosurg: Spine / Volume 17 / November 2012

4 Outcomes after surgery for spinal metastatic leiomyosarcoma Fig. 1. Case 1. Sagittal T2-weighted MR image showing a T-5 pathological fracture and an epidural tumor compressing the spinal cord. metastatic lesions from the literature, as well as those in our series, experienced pain relief and/or neurological recovery.2,3,5,7,9,14,16,18 All 8 patients who underwent surgery in our study had improved Nurick grades and/or pain relief. The improvement in ambulation in all 3 patients who were nonambulatory prior to surgery is a significant consideration for quality of life, even in the setting of a terminal illness. A high recurrence rate was noted among our patients; however, there were a few mitigating factors. The patient in Case 1 initially presented with a T-5 metastasis, and then a metastatic lesion developed at T7 8. One could argue that this event was a new metastasis and not a recurrence, but we elected to categorize it as a recurrence since it occurred within the surgically treated segments J Neurosurg: Spine / Volume 17 / November 2012 Fig. 2. Case 1. Lateral radiograph obtained after a T-5 vertebrectomy, showing interbody cage placement in conjunction with T3 7 posterior fusion. (he had undergone instrumentation at T-7 during his initial surgery). The patient in Case 7 presented to our institution with a recurrence after having undergone surgery the previous year at an outside hospital. This patient had a recurrence just 2.2 months after his repeat surgery at our institution and was not offered further surgery given the progression of his systemic disease. For the remaining 3 patients, intralesional resection was performed, and presumed contamination of the resection cavity likely contributed to recurrence. As with their initial surgeries, the majority of patients who underwent repeat surgery had neurological improvement and/or pain relief. Although no formal recommendations exist regarding adjuvant therapy for spinal leiomyosarcoma, chemotherapy and radiation therapy are commonly used in the treatment of metastatic spinal leiomyosarcoma.5 Six pa435

5 J. E. Ziewacz et al. TABLE 2: Characteristics, clinical details, and outcomes in patients with recurrence Case No. Presentation 1 back pain (VAS Score 2), lower extremity par esthesias & weakness, urinary dysfunction; Nurick Grade 4 3 back pain (VAS Score 9) at time of recurrence noted at 7 mos after initial surgery; new onset paraplegia at 9 mos after initial surgery; Nurick Grade 5 4 severe gait imbalance, lower extremity weakness; Nurick Grade 4 Spinal Level Surgery Outcome T7 8 T7 8 laminectomy & lt T-8 transpedicular approach for tumor resection, extension of fusion to T-9 T1 3 rt T-3 transpedicular tumor approach; partial T-2 & T-3 corpectomies for tumor resection; extension of fusion to T-5 T1 2 redo C7 T2 laminectomy for tumor resection improved back pain (VAS Score 0); VAS Score 4 leg pain attributed to lt femur metastasis; no bladder symptoms; Nurick Grade 3 remained paraplegic; Nurick Grade 5 improved to Nurick Grade 3; recurrence 6 mos later w/ myelopathy (Nurick Grade 4), prompting another tumor resection w/o significant improvement improved leg pain (VAS Score 1) 5 rt leg radiculopathy (VAS score range 2 7) L4 S1 redo L4 S1 laminectomy for tumor resection 7 back pain (VAS Score 3), paraplegia; Nur- T10 12 none remained paraplegic; Nurick Grade 5 ick Grade 5 tients in our series received adjuvant chemotherapy and radiation therapy, 1 (Case 6) received neither, and 1 (Case 8) received chemotherapy. While the patients in Cases 6 and 8 did not have recurrent spinal disease, they did have the shortest survival after surgery. Interestingly, 2 of the 5 patients in the Elhammady et al. 5 study received no adjuvant therapy after what appeared to be intralesional resection and were alive at 3 and 8 years. The impact of adjuvant therapy is therefore unclear, and a larger study is needed. Because of the rarity of spinal metastatic leiomyosarcoma, no definitive statement regarding management can be made. Surgical and therapeutic decision-making must be individually tailored and based on the patient s clinical status, disease prognosis, lesion location, disease burden, and goals of care. However, given the aggressive nature of the disease and the variability in clinical outcomes with the possibility of prolonged survival, aggressive resection and stabilization should be considered when feasible in the well-selected patient with metastatic leiomyosarcoma of the spine. Conclusions Leiomyosarcoma metastatic to the spine is rare and has a predilection for the thoracic and lumbar regions. The clinical course is variable, and relatively prolonged survival is possible. Surgery is likely to improve pain and neurological function. Given the possibility of relatively long-term survival and the locally aggressive nature of the disease, aggressive excision with stabilization should be considered when feasible in the well-selected patient. Disclosure Dr. La Marca is a consultant for Biomet, Globus, and Lanx and has received non study related support from DePuy. Dr. Park is a consultant for Globus and is a past consultant for DePuy Spine. He has also received a non study related honorarium from Medtronic. Author contributions to the study and manuscript preparation include the following. Conception and design: Park, La Marca. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: Park, Ziewacz, Lau. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Park. Study supervision: Park, La Marca. References 1. Abeler VM, Røyne O, Thoresen S, Danielsen HE, Nesland JM, Kristensen GB: Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 54: , Arnesen MA, Jones JW: Spindle cell neoplasm of the thoracic spine. Ultrastruct Pathol 16:29 34, Botwin KP, Zak PJ: Lumbosacral radiculopathy secondary to metastatic uterine leiomyosarcoma: a case report. Spine (Phila Pa 1976) 25: , Ducimetière F, Lurkin A, Ranchère-Vince D, Decouvelaere AV, Péoc h M, Istier L, et al: Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. 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6 Outcomes after surgery for spinal metastatic leiomyosarcoma ifestation of metastasizing leiomyosarcoma. Spine (Phila Pa 1976) 24: , Nishida J, Kato S, Shiraishi H, Ehara S, Sato T, Okada K, et al: Leiomyosarcoma of the lumbar spine: case report. Spine (Phila Pa 1976) 27:E42 E46, Nurick S: The pathogenesis of the spinal cord disorder associated with cervical spondylosis. Brain 95:87 100, Ochiai H, Yamakawa Y, Fukushima T, Yamada H, Hayashi T: Primary leiomyosarcoma of the cervical spine causing spontaneous compression fracture: report of an autopsy case. Neuropathology 20:60 64, Potsi M, Stavrinou P, Patsinakidis N, Hatzibougias D, Foroglou N, Karayanopoulou G, et al: Primary osseous leiomyosarcoma of the spine: a rare entity case report and review of the literature. J Neurol Surg A Cent Eur Neurosurg 73: , Shapiro S: Myelopathy secondary to leiomyosarcoma of the spine. Case report. Spine (Phila Pa 1976) 17: , Skubitz KM, D Adamo DR: Sarcoma. Mayo Clin Proc 82: , Sucu HK, Bezircioglu H, Rezanko T: Partial spondylectomy for primary leiomyosarcoma of C2 vertebra. Spine (Phila Pa 1976) 36:E1422 E1426, Svarvar C, Böhling T, Berlin O, Gustafson P, Follerås G, Bjerkehagen B, et al: Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group. Cancer 109: , Takemori M, Nishimura R, Sugimura K, Mitta M: Thoracic vertebral bone metastasis from uterine leiomyosarcoma. Gynecol Oncol 51: , 1993 Manuscript submitted March 30, Accepted August 2, Please include this information when citing this paper: published online August 31, 2012; DOI: / SPINE Address correspondence to: Paul Park, M.D., Department of Neurosurgery, University of Michigan Health System, 1500 East Medical Center Drive, Room 3552 TC, Ann Arbor, Michigan ppark@umich.edu. J Neurosurg: Spine / Volume 17 / November