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Rachel Grossman, Betty Tyler, Lee Hwang, Patti Zadnik, Bachchu Lal, Kashi Javaherian and Henry Brem

Object

Brain tumors pose many unique challenges to treatment. The authors hypothesized that Fc-endostatin may be beneficial. It is a newly synthesized recombinant human endostatin conjugated to the Fc domain of IgG with a long half-life (weeks) and unknown toxicity. The authors examined the efficacy of Fc-endostatin using various delivery methods.

Methods

Efficacy was assessed using the intracranial 9L gliosarcoma rat model treated with Fc-endostatin for use in rodents (mFc-endostatin), which was administered either systemically or locally via different delivery methods. Oral temozolomide (TMZ) was administered in combination with mFc-endostatin to determine if there was a beneficial synergistic effect.

Results

Intracranial delivery of mFc-endostatin via a polymer or convection-enhanced delivery 5 days after tumor implantation increased median survival, compared with the control group (p = 0.0048 and 0.003, respectively). Animals treated weekly with subcutaneous mFc-endostatin (started 5 days post–tumor implantation) also had statistically improved survival as compared with controls (p = 0.0008). However, there was no statistical difference in survival between the local and systemic delivery groups. Control animals had a median survival of 13 days. Animals treated either with subcutaneous mFc-endostatin weekly or with polymer had a median survival of 18 and 15 days, respectively, and those treated with oral TMZ for 5 days (Days 5–9) had a median survival of 21 days. Survival was further increased with a combination of oral TMZ and mFc-endostatin polymer, with a median survival of 28 days (p = 0.029, compared with TMZ alone). Subcutaneous mFc-endostatin administered every week starting 18 days before tumor implantation significantly increased median survival when compared with controls (p = 0.0007), with 12.5% of the animals ultimately becoming long-term survivors (that is, survival longer than 120 days). The addition of TMZ to either weekly or daily subcutaneous mFc-endostatin and its administration 18 days before tumor implantation significantly increased survival (p = 0.017 and 0.0001, respectively, compared with TMZ alone). Note that 12.5% of the animals treated with weekly subcutaneous mFc-endostatin and TMZ were long-term survivors.

Conclusions

Systemically or directly (local) delivered mFc-endostatin prolonged the survival of rats implanted with intracranial 9L gliosarcoma. This benefit was further enhanced when mFc-endostatin was combined with the oral chemotherapeutic agent TMZ.

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Daniel M. Sciubba, Mohamed Macki, Mohamad Bydon, Niccole M. Germscheid, Jean-Paul Wolinsky, Stefano Boriani, Chetan Bettegowda, Dean Chou, Alessandro Luzzati, Jeremy J. Reynolds, Zsolt Szövérfi, Patti Zadnik, Laurence D. Rhines, Ziya L. Gokaslan, Charles G. Fisher and Peter Paul Varga

OBJECT

Clinical outcomes in patients with primary spinal osteochondromas are limited to small series and sporadic case reports. The authors present data on the first long-term investigation of spinal osteochondroma cases.

METHODS

An international, multicenter ambispective study on primary spinal osteochondroma was performed. Patients were included if they were diagnosed with an osteochondroma of the spine and received surgical treatment between October 1996 and June 2012 with at least 1 follow-up. Perioperative prognostic variables, including patient age, tumor size, spinal level, and resection, were analyzed in reference to long-term local recurrence and survival. Tumor resections were compared using Enneking appropriate (EA) or Enneking inappropriate surgical margins.

RESULTS

Osteochondromas were diagnosed in 27 patients at an average age of 37 years. Twenty-two lesions were found in the mobile spine (cervical, thoracic, or lumbar) and 5 in the fixed spine (sacrum). Twenty-three cases (88%) were benign tumors (Enneking tumor Stages 1–3), whereas 3 (12%) exhibited malignant changes (Enneking tumor Stages IA–IIB). Sixteen patients (62%) underwent en bloc treatment—that is, wide or marginal resection—and 10 (38%) underwent intralesional resection. Twenty-four operations (92%) followed EA margins. No one received adjuvant therapy. Two patients (8%) experienced recurrences: one in the fixed spine and one in the mobile spine. Both recurrences occurred in latent Stage 1 tumors following en bloc resection. No osteochondroma-related deaths were observed.

CONCLUSIONS

In the present study, most patients underwent en bloc resection and were treated as EA cases. Both recurrences occurred in the Stage 1 tumor cohort. Therefore, although benign in character, osteochondromas still require careful management and thorough follow-up.