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

Beril Gok, Matthew McGirt, Daniel Sciubba, Selim Ayhan, Ali Bydon, Timothy F Witham, Jean Paul Wolinsky, Ziya L. Gokaslan

Research output: Contribution to journalArticle

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 ≤ 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)346-351
Number of pages6
JournalNeurosurgery
Volume63
Issue number2
DOIs
StatePublished - Aug 2008

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Adjuvant Radiotherapy
Radiotherapy
Neoplasms
Spinal Cord Compression
Spine
Therapeutics
Extremities
Animal Models
Control Groups
Inbred F344 Rats
Paresis
Polymethyl Methacrylate
Walking

Keywords

  • Metastatic spinal tumor
  • Radiotherapy
  • Rat
  • Surgery

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

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. / Gok, Beril; McGirt, Matthew; Sciubba, Daniel; Ayhan, Selim; Bydon, Ali; Witham, Timothy F; Wolinsky, Jean Paul; Gokaslan, Ziya L.

In: Neurosurgery, Vol. 63, No. 2, 08.2008, p. 346-351.

Research output: Contribution to journalArticle

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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 ≤ 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). Conclusion: 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.",
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AU - Gok, Beril

AU - McGirt, Matthew

AU - Sciubba, Daniel

AU - Ayhan, Selim

AU - Bydon, Ali

AU - Witham, Timothy F

AU - Wolinsky, Jean Paul

AU - Gokaslan, Ziya L.

PY - 2008/8

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N2 - 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 ≤ 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). Conclusion: 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.

AB - 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 ≤ 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). Conclusion: 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.

KW - Metastatic spinal tumor

KW - Radiotherapy

KW - Rat

KW - Surgery

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