title: Surgical resection plus adjuvant radiotherapy is superior to surgery or radiotherapy alone in the prevention of neurological decline in a rat metastatic spinal tumor model.
abstract: OBJECTIVE
  The optimal management of spinal column metastatic disease is controversial. Furthermore, the literature lacks an accurate animal model to study the efficacy of surgical treatment options for spinal column metastases. We compared the efficacy of surgery, radiotherapy, or surgery plus adjuvant radiotherapy in a rat model of metastatic epidural spinal cord compression.
  
  
  METHODS
  Thirty-two Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L6. Animals were randomly assigned to receive one of four treatments (n = 8 per group) 7 days after tumor implantation: 1) control: no treatment; 2) external beam radiation therapy (XRT) (total 20 Gy in 400-cGy daily fractions); 3) surgery: L6 vertebral corpectomy, tumor resection, and polymethyl methacrylate reconstruction; and 4) surgery + XRT: corpectomy and tumor resection followed by XRT (total 20 Gy in 400-cGy daily fractions) 72 hours after surgery. Hind-limb function was tested daily after treatment using the Basso-Beattie-Bresnahan (BBB) scale (range, 1-21).
  
  
  RESULTS
  All animals (n = 32) demonstrated normal hind-limb function (BBB score, 21) on posttreatment Day 1. The XRT, surgery, and surgery + XRT groups all experienced a delay in onset of paresis versus the control group. Compared to the XRT group, the surgery group demonstrated greater median BBB scores on Days 3 (21 versus 20, P = 0.02) through 9 (12 versus 8, P = 0.002) after treatment. Compared with the surgery group, the surgery + XRT group demonstrated even greater median BBB scores on Days 6 (21 versus 19, P = 0.0008) through 11 (16 versus 8, P = 0.0001) after treatment. Median time to loss of ambulation (BBB <or= 7) was greatest in the surgery + XRT group (15 d) when compared with the surgery (12 d, P = 0.001), XRT (9 d, P = 0.001), or control groups (7 d, P = 0.0005).
  
  
  CONCLUSIONS
  In a rat model of metastatic epidural spinal cord compression, decompressive surgery followed by radiotherapy yielded the greatest efficacy in the prevention of neurological decline when compared with surgery or radiotherapy alone. Radiotherapy alone attenuated neurological decline but was the least efficacious treatment in this model. These results support this animal model as an effective platform to investigate novel interventions for metastatic spine tumors.
authors.affiliation: Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Beril
authors.initials: B
authors.lastname: Gok
authors.forename: Matthew
authors.initials: M
authors.lastname: McGirt
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sciubba
authors.forename: Selim
authors.initials: S
authors.lastname: Ayhan
authors.forename: Ali
authors.initials: A
authors.lastname: Bydon
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Witham
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Wolinsky
authors.forename: Ziya L
authors.initials: ZL
authors.lastname: Gokaslan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant; D051381:Rats; D011916:Rats, Inbred F344; D013120:Spinal Cord Neoplasms / Q000150:complications / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery*