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Rajiv R. Iyer, Xiaobu Ye, Qiuyu Jin, Yao Lu, Luckmini Liyanage and Edward S. Ahn

OBJECTIVE

Many infants with sagittal craniosynostosis undergo effective surgical correction with endoscopic strip craniectomy (ESC) and postoperative helmet therapy (PHT). While PHT is essential to achieving optimal cosmesis following ESC, there has been little comprehensive analysis of the ideal PHT duration needed to attain this goal.

METHODS

The authors retrospectively reviewed the charts of infants undergoing ESC and PHT for sagittal synostosis at our institution between 2008 and 2015. Data collected included age at surgery, follow-up duration, and PHT duration. Cephalic index (CI) was evaluated preoperatively (CIpre), at its peak level (CImax), at termination of helmet therapy (CIoff), and at last follow-up (CIfinal). A multivariate regression analysis was performed to determine factors influencing CIfinal.

RESULTS

Thirty-one patients (27 male, 4 female) were treated in the studied time period. The median age at surgery was 2.7 months (range 1.6 to 3.2) and the median duration of PHT was 10.4 months (range 8.4 to 14.4). The mean CImax was 0.83 (SD 0.01), which was attained an average of 8.4 months (SD 1.2) following PHT initiation. At last follow-up, there was an average retraction of CIfinal among all patients to 0.78 (SD 0.01). Longer helmet duration after achieving CImax did not correlate with higher CIfinal values. While CImax was a significant predictor of CIfinal, neither age at surgery nor CIpre were found to be predictive of final outcome.

CONCLUSIONS

Patients undergoing ESC and PHT for sagittal synostosis reach a peak CI around 7 to 9 months after surgery. PHT beyond CImax does not improve final anthropometric outcomes. CIfinal is significantly dependent on CImax, but not on age, nor CIpre. These results imply that helmet removal at CImax may be appropriate for ESC patients, while helmeting beyond the peak does not change final outcome.

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Hansen Bow, Lee S. Hwang, Noam Schildhaus, Joanna Xing, Luke Murray, Quinn Salditch, Xiaobu Ye, Yonggang Zhang, Jon Weingart, Henry Brem and Betty Tyler

Object

Over the past several years, there has been increasing interest in combining angiogenesis inhibitors with radiotherapy and temozolomide chemotherapy in the treatment of glioblastoma. Although the US FDA approved bevacizumab for the treatment of glioblastoma in 2009, the European Medicines Agency rejected its use due to its questionable impact on patient survival. One factor contributing to the failure of angiogenesis inhibitors to increase overall patient survival may be their inability to cross the blood-brain barrier. Here the authors examined in a 9L glioma model whether intracranial polymer-based delivery of the angiogenesis inhibitor minocycline potentiates the effects of both radiotherapy and temozolomide chemotherapy in increasing median survival. The authors also investigated whether the relative timing of minocycline polymer implantation with respect to radiotherapy affects the efficacy of radiotherapy.

Methods

Minocycline was incorporated into the biodegradable polymer polyanhydride poly(1,3-bis-[p-carboxyphenoxy propane]-co-[sebacic anhydride]) (CPP:SA) at a ratio of 50:50 by weight. Female Fischer 344 rats were implanted with 9L glioma on Day 0. The minocycline polymer was then implanted on either Day 3 or Day 5 posttumor implantation. Cohorts of rats were exposed to 20 Gy focal radiation on Day 5 or were administered oral temozolomide (50 mg/kg daily) on Days 5–9.

Results

Both minocycline polymer implantations on Days 3 and 5 increased survival from 14 days to 19 days (p < 0.001 vs control). Treatment with a combination of both minocycline polymer and radiotherapy on Day 5 resulted in a 139% increase in median survival compared with treatment with radiotherapy alone (p < 0.005). There was not a statistically significant difference in median survival between the group that received minocycline implanted on the same day as radiotherapy and the group that received minocycline polymer 2 days prior to radiotherapy. Lastly, treatment with a combination of minocycline polymer with oral temozolomide resulted in a 38% extension of median survival compared with treatment of oral temozolomide alone (p < 0.001).

Conclusions

These results show that minocycline delivered locally potentiates the effects of both radiotherapy and oral temozolomide in increasing median survival in a rodent glioma model. More generally, these results suggest that traditional therapy in combination with local, as opposed to systemic, delivery of angiogenesis inhibitors may be able to increase median survival for patients with glioblastoma.