Abstract

Background: Gastrointestinal stromal tumors (GISTs) very rarely metastasize to the vertebrae. Tyrosine kinase inhibitors (TKIs) confer favorable long-term survival and durable disease control for metastatic disease. Here, we reviewed a case and the literature to determine the various management options, and neurological outcomes for these patients.

Case Description: A 63-year-old Chinese female with metastatic jejunal GIST previously treated with various TKIs presented with the left lower limb weakness and a sensory level at T10. MRI revealed a T9 vertebral body tumor with cord compression. The tumor was excised and surgical fixation was performed. She received 30Gy of fractionated adjuvant radiotherapy. She achieved near-complete neurological recovery but died 2 months later from systemic disease progression.

Conclusion: Based on this case and a review of the literature, surgical intervention and treatment with TKIs with adjuvant RT can lead to comparable survival and neurological outcomes.

Keywords: Gastrointestinal stromal tumor, Spine metastasis, Spine surgery, Vertebral metastasis

INTRODUCTION

Metastasis of gastrointestinal stromal tumor (GIST) to the vertebral column is very rare; there are only a handful of reported cases in the literature. Tyrosine kinase inhibitors (TKIs) (e.g., imatinib mesylate) have significantly prolonged survival in metastatic GIST,[ 2 ] with response rates in excess of 80%.[ 11 ] Responses have been reported as rapid and durable, with a median time-to-response of 13 weeks, lasting for more than 46 weeks.[ 10 ] Unlike many other common metastatic malignancies, survival beyond 6 years can be expected for patients with metastatic GISTs.[ 4 , 22 ] These are important considerations, as radiotherapy (RT) for symptom relief and TKIs for tumor control may also be reasonable nonsurgery-based alternatives.

Here, we report a case of metastatic vertebral GIST, and provide a summary of the current literature regarding treatment options, and long-term survival/neurological outcomes for these patients.

METHODS

Literature review

PubMed and MEDLINE were searched using the term “(GIST OR (gastrointestinal AND stromal)) AND (spine OR spinal OR vertebral)” on April 11, 2019. It yielded 47 results; Chinese, Japanese, and English articles were assessed. Patient characteristics were identified and summarized. Kaplan– Meier analysis was used to estimate the median overall survival, 1-year and 2-year survivals by pooling outcome data from individual case reports or series. Python version 3.7, and the lifelines package were used to perform survival analyses.[ 9 ]

CASE REPORT

History, examination, and imaging

A 63-year-old Chinese female presented with 1-week history of progressive thoracolumbar back pain and left leg weakness with a T10 sensory level with preservation of sphincter function. She had been diagnosed with jejunal GIST 5 years previously and had known metastases to the liver, mesenteric lymph nodes, pelvis, and bladder. She had already received multiple lines of TKIs (imatinib, sunitinib, regorafenib, and dasatinib). The holospinal MR revealed a T9 enhancing lesion with an associated pathological fracture, spinal cord compression, and cord edema [ Figure 1 ]. Small asymptomatic enhancing lesions were also noted involving the L5 vertebral body and L1 spinous process [ Figure 2 ].

Figure 1:

(a) Postcontrast T1 sagittal, (b) T2 sagittal, and (c) T1 axial MRI images showing anterior compression of the spinal cord from epidural extension of the lesion at the T9 vertebra.

Figure 2:

Asymptomatic enhancing lesions at the L1 spinous process and L5 vertebral body.

Operation

She underwent a T9 decompressive laminectomy for tumor excision and an instrumented fusion from T7 to T11; the diseased left T9 pedicle was excised. The tumor was gray, soft, friable, and hyper-vascular. The extradural component anterior to the cord was removed, and the cord was adequately decompressed.

Histopathology

The histopathology confirmed the diagnosis of metastatic GIST. It revealed lamellar bone fragments with nests and cords of epithelioid cells accompanied by moderate anisonucleosis, fair amounts of cytoplasm, and gland-like spaces in some areas. Background myxoid features were also noted. The tumor stained weakly for KIT (CD117), strongly for DOG-1, and negative for S-100, HMB45, desmin, CD31, ERG, Cam5.2, and AE1/3.

Postoperative course

Following surgery, she had no surgery-related complications, and nearly-completely recovered neurological function with a short rehabilitation stay. Adjuvant RT of 30 grays over ten fractions was administered from T7 to T11. Some residual back pain was noted and treated with oral analgesics. Postoperative X-rays demonstrated adequate location of instrumentation and preservation of alignment [ Figure 3 ]. Two months later she developed disease progression with peritoneal carcinomatosis with ascites, and expired.

Figure 3:

T7 to T11 instrumentation and fixation, T9 laminectomy and excision of tumor. (a) Anterior-posterior film and (b) lateral film.

RESULTS

Patient demographics

From literature search, we identified nine patients (including this case) with metastatic vertebral GIST who were treated surgically. Four of these had neurological deficits: 2 motor, 1 sensory, and 1 malignant cord compression presenting with cauda equina syndrome [ Table 1 ].

Table 1:

Summary of surgically managed metastatic GIST to the vertebra published in the literature (excluding percutaneous biopsies). Gy: Gray (cGy: centi-Gray). RT, radiotherapy.

There were “20 patients” managed non-surgically, whose baseline clinical characteristics were similar to the surgical patient population. Interestingly, they averaged 10 years older than the surgical patients (64 years old vs. 54 years old, respectively), and seven presented with motor/sensory deficits, while 11 had pain alone. There were no other statistically significant differences in baseline clinical characteristics between the surgical and non-surgical groups [ Table 2 ]; [ Table 3 for a summary of non-surgically treated patients].

Table 2:

Comparison of surgically managed and non-surgically managed patients.

Table 3:

Summary of all available case reports of metastatic GIST to the vertebra in the literature.

Pattern of vertebral metastasis

The lumbar (39%) and thoracic (39%) regions were the most common sites, followed by the sacrum (24%), and lastly, the cervical (15%) spine. Twenty (61%) of these patients also had bone metastases mainly involving the axial skeleton. In addition, 26 patients (79%) had visceral involvement, and 23 patients (70%) had liver metastasis. GIST tumors arose from a variety of locations: eleven from the small intestinal (33%), ten gastric (30%), six colorectal (18%), and six from extra-gastrointestinal sites [ Table 3 ].

Survival outcomes

The median overall survival of 27 patients, from time of diagnosis of vertebral GIST, was 34 months; 1-year survival was 74%, and 2-year survival was 56%. The survival curves for those managed surgically versus “non-surgically” did not differ significantly; in the surgical cohort, the median survival was 24 months, while in the nonsurgery cohort, it was 34 months [ Figure 4 ].

Figure 4:

Kaplan-Meier plot of pooled survival data from literature review of all 27 reported cases of GIST with spinal metastases.

Neurological outcomes

Rates of residual neurological deficits were comparable between the two groups [ Table 1 ].

DISCUSSION

Metastatic GIST

GISTs are rare mesenchymal tumors and constitute 0.1%–3% of all gastrointestinal neoplasms. They most commonly involve the stomach (60%), small intestine (15%), colon/ rectum (5%), and visceral organs (omentum) mesentery (5%).[ 29 ] Metastases commonly involve the liver and peritoneum.[ 29 ]

Genetics and chemotherapy

Most GISTs stain positive for KIT (CD117) and DOG-1. The identification of driver mutations in the KIT or PDGFRA (platelet-derived growth factor receptor alpha) genes led to the development of TKIs such as imatinib and sunitinib which significantly improved the survival of these patients.[ 20 ] In some studies, metastatic GIST in general is expected to survive for over 6 years following treatment with TKIs. In our case, vertebral metastases developed despite four lines of TKIs, which likely contributed to the rapid disease progression following surgery.

Treatment considerations

Most vertebral GIST metastases are symptomatic; 80% present with pain, and 38% with neurological deficits.

Comparison of all reported cases failed to show a significant difference in the median overall survival (24 vs. 34 months, P = 0.56) or neurological outcome (17% vs. 20% residual deficits, P = 0.87) between those managed surgically versus “non-surgically” (e.g., with TKIs and RT).

CONCLUSION

Metastatic GIST to the vertebral bodies is rare, and these patients have median survivals of 34 months. Successful treatment may include surgical and nonsurgical (TKIs and RT) options.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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