Garth T. Olson

A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma

OBJECTIVES The epidermal growth factor receptor (EGFR) is a validated target in head and neck squamous cell carcinoma (HNSCC). In recurrent and/or metastatic (R/M) HNSCC, resistance to anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/Akt/mTOR pathway is an established resistance mechanism. Concurrent mTOR blockade may improve efficacy of anti-EGFR therapy. MATERIALS AND METHODS Erlotinib 150 mg daily and temsirolimus 15 mg weekly were administered to patients with platinum-refractory R/M HNSCC and ECOG performance status 0-2. The primary endpoint was progression-free survival (PFS). Correlative studies determined PIK3CA and HRAS mutation status; p16, EGFR, pS6K, pAkt and PTEN expression; and pre- and post-treatment plasma levels of 20 immunomodulatory cytokines. RESULTS Twelve patients enrolled; six withdrew within 6 weeks due to toxicity or death, prompting early closure of the trial. Grade ≥ 3 toxicities included fatigue, diarrhea, gastrostomy tube infection, peritonitis, pneumonia, dyspnea, and HN edema. Median PFS was 1.9 months. Median overall survival was 4.0 months. Six/12 tumors were p16(+), 9/11 lacked measurable PTEN expression, and 1/12 harbored a PIK3CA mutation. On exploratory analysis, high baseline plasma VEGF and interferon-gamma levels marginally associated with tumor progression. CONCLUSIONS The combination of erlotinib and temsirolimus was poorly tolerated. Low prevalence of PTEN expression and 8% incidence of PIK3CA mutations indicate biological relevance of this pathway in R/M disease. Investigation of more tolerable combinations of EGFR and PI3K/Akt/mTOR pathway inhibitors in selected HNSCC patients is warranted.

Biomechanical optimization of bone plates used in rigid fixation of mandibular symphysis fractures.

PURPOSE To design and optimize a bone plate for fractures of the mandibular symphysis that will provide maximum fracture stability with minimal implanted volume and patient intrusion. The design will be driven by the unique biomechanics specific to this fracture location. MATERIALS AND METHODS A finite element model of a fractured human mandible was created using computed tomography scans. The boundary conditions included simulating molar, canine, and incisal loading. The bone plate design process included a shape optimization routine and design parameter analysis using the model. The optimized bone plate design was finally compared with standard bone plate configurations according to stress and strain measures. RESULTS Compared with the miniplate combination, the InterFlex III plate, with the same thickness and just 14% more implanted volume, had only 55% of the plate stress and 25% less fracture strain under the strongest loads considered by the model. Compared with the band/fracture plate combination, the InterFlex plate had 88% of the fracture strain and 74% of the plate stress, despite having only 60% of the plate volume. CONCLUSIONS The results have demonstrated that the new optimized plate is a hybrid of fixation hardware with the small profile of the smallest miniplate configuration and the superior fixation strength and safety that exceeds that of the larger fracture plate configuration.

Minimally invasive bioabsorbable bone plates for rigid internal fixation of mandible fractures.

OBJECTIVES To optimize design variables of a bioabsorbable bone plate using a finite element model of the mandible and to discover a minimally invasive bioabsorbable bone plate design that can provide the same mechanical stability as a titanium plate. METHODS A finite element model of a mandible with a fracture in the body was subjected to bite loads. An analysis was run to determine the principal strain in the fracture callus and von Mises stress in a titanium plate. These values were then set as the limits within which the bioabsorbable bone plate must comply. The model then considered a bone plate made of the polymer poly(L-lactide-co-D,L-lactide) (P[L/DL]LA) 70/30. An optimization routine determined the smallest volume of bioabsorbable bone plate that can perform as well as a titanium bone plate when fixating mandibular fractures. RESULTS A P(L/DL)LA plate volume of 315 mm(2) with a thickness of 1.5 mm provided as much mechanical stability as a commonly used titanium strut structure of 172 mm(2). The peak plate stress was well below the yield strength of the material. CONCLUSIONS The P(L/DL)LA bioabsorbable bone plate design is as strong as a titanium plate when fixating fractures of the mandible body despite the polymer material having only 6% of the stiffness of the titanium. The P(L/DL)LA plate can be less than half the volume of its strut-style counterpart.

Longitudinal voice outcomes following laryngeal reinnervation via vagus-to-recurrent laryngeal nerve anastomosis after vagal nerve sacrifice: a case series.

Objective: This study aimed to describe longitudinal voice outcomes of vagus-to-recurrent laryngeal nerve anastomosis following operative vagal nerve sacrifice. Methods: Two patients who underwent anastomosis were assessed by a multidisciplinary voice team at 1, 4, 9, 12, and 18 months after vagal sacrifice. Results: Long-term changes in voice function based on auditory perceptual measures of voice quality and visual perceptual changes in glottal closure were observed and maintained for 18 months after vagus-to-recurrent laryngeal nerve anastomosis in 2 patients with proximal vagal nerve sacrifice. Patients achieved acceptable voice outcomes and elected not to undergo further treatment, which was supported by Voice Handicap Index scores. Conclusion: Gradual restoration of voice following operative vagal sacrifice can be achieved over an 18-month period using vagus-to-recurrent laryngeal nerve anastomosis and warrants further investigation in appropriately selected patients.

Reconstruction of Periparotid Defects Using Temporoparietal Fascia Flap with Layered Acellular Human Dermal Allograft

Excision of lesions in the periparotid area can leave a sizable concavity of the preauricular area with skeletonization of the mandible. To achieve the bulk necessary to fill this defect, we propose using a composite graft. Acellular human dermal allograft provides the thickness of the graft, and the temporoparietal fascia flap provides blood supply to the dermal graft. Our hypothesis is that vascularization of the graft will promote greater ingrowth of native tissue and prevent breakdown and absorption of the graft. Four representative patients are described.

Digital microphotography: A simple solution

INTRODUCTION Photographic documentation is an essential technique in the practice of otolaryngology—head and neck surgery and all of its subspecialties. Photographs, both on film and digitally archived, detail patient conditions, accurately depict portions of a surgical procedure, and complement verbal descriptions in communication with patients and colleagues. In addition, photographs serve as essential teaching tools, and they provide valuable documentation in medicolegal cases. Since its advent in the 1970s, digital photography has rapidly developed into a commonly accepted means of photodocumentation. With the incredible pace of technological innovation and the accompanying decrease in the costs of computers and digital technology, digital cameras are ubiquitous in the hospital environment today. Although several systems are currently in use that are capable of acquiring images through an operating microscope, these devices typically involve both additional equipment and expense. We use a simple technique for digital microphotography that carries only minimal expense and provides high-quality digital images that rival those produced by any existing system. By using the same camera system to take standard photographs as well as images from the microscope, digital acquisition and archiving of patient records are streamlined. This technique may be reliably and reproducibly applied to otology, microvascular surgery, neurosurgery, and laryngology, as well as the clinical setting.