Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.

Calvarial Reconstruction Following Massive Tissue Loss: A Feasible Treatment Strategy and Surgical Technique.

BACKGROUND: Severe cranial injuries require reconstructive surgeries to protect the underlying brain and to restore cranial contour and scalp integrity, as well as avoid complications such as neurocognitive decline. In cases of full-thickness cranial tissue damage, adept surgical skill in both bone and soft tissue reconstruction is critical for a minimally invasive surgery and successful bone integration without endangering previous soft tissue efforts. Different surgical techniques and materials are beset with various problems. OBJECTIVE: To present a surgical procedure intended for the reconstruction of complex calvarial and associated tissue defects with reduced invasiveness and improved soft tissue healing compared to the existing gold standard. Both soft tissue and bone reconstruction techniques are described in detail due to their intertwined importance for successful full thickness skull and scalp reconstruction. METHODS: During initial medical care, aseptic wound treatment and temporary wound closure are performed. Two weeks postinjury, extensive necrotic tissue debridement and soft tissue reconstruction lay the foundation for well-vascularized tissue regeneration. Soft tissue healing is followed by minimally invasive cranioplasty using autologous split-rib transplants after approximately 6 mo. RESULTS: With consideration of the established gold standards for treatment, soft tissue regenerated without complications. The minimally invasive insertion of autologous rib grafts underneath the healed soft tissue allowed for quick recovery without requiring further follow-up treatments. CONCLUSION: We optimized initial scalp wound healing and bone regeneration by making use of minimally invasive procedures and autologous materials, offering a viable treatment alternative to existing methods for treating large cranial bone injuries.

Vertebral autograft used as bone transplant for anterior cervical corpectomy: technical note.

OBJECTIVE: In this prospective patient study, we used a surgical technique for autograft bone fusion during anterior cervical corpectomy (ACC) in patients experiencing cervical spondylotic myelopathy. We packed the resected bone material of the corpectomy into a titanium mesh cage. To evaluate the efficacy of our autograft technique, we analyzed the results according to neurological outcome, radiological outcome, and complications. METHODS: Between 1995 and 1998, 27 ACC operations were performed for cervical spondylotic myelopathy caused by multisegmental cervical spondylosis. In all patients, decompression of the cervical canal and/or spinal nerve roots was performed by a median cervical corpectomy by an anterior approach. After the ACC was completed, a titanium mesh cage, which was variable in diameter and length, was filled with morselized and impacted bone material from the cervical corpectomy and was then implanted. An anterior cervical plate was placed in all patients to achieve primary stability of the cervical vertebral column. Age, sex, pre- and postoperative myelopathy, number of decompressed levels, radiological results, and complications were assessed. The severity of myelopathy was graded according to the scoring system of the Japanese Orthopaedic Association. RESULTS: Symptomatic improvement of neurological deficits was achieved in 80% of the patients. The mean preoperative Japanese Orthopaedic Association score improved from 13.1 to 15.2 postoperatively (P < 0.05). No patient demonstrated worsening of myelopathic symptoms. Radiological follow-up studies demonstrated complete bony fusion in all patients. A vertical movement of 2.25 +/- 0.43 mm of the titanium cage into the adjacent vertebral bodies was observed in 24 patients. In patients with either a lordotic or neutral cervical spinal axis postoperatively, the axis remained unchanged during the entire follow-up period. CONCLUSION: The results of this study demonstrate that transplantation of autograft bone material harvested during the ACC integrated well in the cage and in the adjacent vertebral bodies. Thus, complications associated with explantation of autograft material from other donor sites, e.g., the iliac crest, could be avoided. The early postoperative and midterm follow-up periods provided no evidence of morphological or functional instability of the operated cervical segments when this autograft technique was used in combination with cervical instrumentation.