Julie A. Goddard

A patient tumor transplant model of squamous cell cancer identifies PI3K inhibitors as candidate therapeutics in defined molecular bins

Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from HNSCC patients, both HPV+ and HPV−, were implanted on mice, giving rise to 25 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA‐sequencing. Drug efficacy studies were run with representative xenografts using the approved drug cetuximab as well as the new PI3K inhibitor PX‐866. Tumors maintained their original morphology, genetic profiles and drug susceptibilities through serial passaging. The genetic makeup of these tumors was consistent with known frequencies of TP53, PI3KCA, NOTCH1 and NOTCH2 mutations. Because the EGFR inhibitor cetuximab is a standard HNSCC therapy, we tested its efficacy and observed a wide spectrum of efficacy. Cetuximab‐resistant strains had higher PI3K/Akt pathway gene expression and protein activation than cetuximab‐sensitive strains. The PI3K inhibitor PX‐866 had anti‐tumor efficacy in HNSCC models with PIK3CA alterations. Finally, PI3K inhibition was effective in two cases with NOTCH1 inactivating mutations. In summary, we have developed an HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. This model enables to prospectively test therapeutic‐oriented hypotheses leading to personalized medicine.

A comparison of overall survival for patients with T4 larynx cancer treated with surgical versus organ-preservation approaches: A National Cancer Data Base analysis.

Although laryngectomy is the treatment of choice for patients with T4 larynx cancer, many patients are unable or unwilling to undergo laryngectomy and instead pursue larynx‐preservation strategies combining radiotherapy (RT) and chemotherapy. Herein, the authors analyzed the National Cancer Data Base to evaluate overall survival (OS) between patients treated with surgical and organ‐preserving modalities.

Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis

Adding induction chemotherapy to concurrent chemotherapy and radiotherapy (RT) has generally not improved the overall survival (OS) in randomized trials of patients with head and neck cancer. This failure may stem from inadequate power or inappropriate patient selection, prompting this National Cancer Data Base analysis.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies

Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality.

Antibiotic prophylaxis in clean-contaminated head and neck cases with microvascular free flap reconstruction: A systematic review and meta-analysis

Optimal antibiotic prophylaxis duration in head and neck clean‐contaminated free‐flap cases is unknown.

The Utility of In-Office Ultrasound in the Diagnosis of Parotid Lesions.

Objective To determine whether the use of in-office ultrasound (US) by a head and neck surgeon is a useful adjunct to clinical assessment of parotid lesions and decrease the need of additional imaging, such as magnetic resonance imaging (MRI) or computed tomography (CT). Study Design Case series with chart review. Setting Tertiary care academic center. Subjects Seventy patients presenting with a parotid lesion who obtained an in-office US and ultrasound-guided fine-needle aspiration (USGFNA) from a head and neck surgeon from 2006 to 2015. Methods US images were retrospectively reviewed for 70 patients and characterized by a radiologist and a head and neck surgeon. Results Of the 70 patients, 6 had US characteristics that demonstrated a statistically significant association with a benign/malignant diagnosis: depth from surface; irregular borders; presence of calcifications, which included either micro- or macro-calcifications; posterior echogenicity enhancement; irregular shape; and homogeneous/heterogeneous echotexture. Imaging was performed prior to referral in 25 cases (35.7%); of those, 17 (68%) were for superficial, small (<2 cm) tumors where prereferral imaging studies did not provide additional information to that obtained with US. Of the 55 patients without MRI or CT performed prior to referral, MRI or positron emission tomography–CT scan was obtained in only 4 patients (7.3%) in cases involving recurrent parotid lesions, large tumors, or workup of a malignant neoplasm. Conclusions Several US characteristics individually assist in lesion characterization. In-office US and USGFNA are an appropriate first-line modality in the assessment of parotid lesions, can allow for immediate parotid lesion assessment, and can decrease the need for additional imaging.

Nomogram for preoperative prediction of nodal extracapsular extension or positive surgical margins in oropharyngeal squamous cell carcinoma

INTRODUCTION Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making. METHODS Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM. RESULTS 5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p < 0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T-classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61 and HPV- 11.66, p = 0.17). CONCLUSIONS These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC.

Free Flap Versus Pedicled Flap Reconstruction of Laryngopharyngeal Defects: A 10-Year National Surgical Quality Improvement Program Analysis: Laryngopharyngeal Reconstruction

Large defects after total laryngectomy (TL) and total laryngopharyngectomy (TLP) often benefit from free flap (FF) or pedicled flap (PF) reconstruction to maintain continuity of the aerodigestive tract, protect great vessels, or reinforce pharyngeal closure. Although both techniques are commonly used, no consensus exists as to which results in fewer complications. The goal of this study was to determine if 30‐day morbidity/mortality outcomes differ between PF and FF reconstruction in patients undergoing TL/TLP.

Current practice trends in microvascular free flap reconstruction by fellowship-trained otolaryngologists

PURPOSE In the field of head and neck microvascular surgery, there are currently no clear, universally accepted recommendations on the intraoperative, preoperative, and postoperative management of these patients. MATERIALS AND METHODS A 23-question cross-sectional survey was distributed to otolaryngologists who perform microvascular reconstruction. Information about practice setting, fellowship training background, intraoperative practice, postoperative practice, and surgical complications were analyzed. RESULTS Complete survey responses were received from 102 (32.8% response rate) of surveyed otolaryngologists who perform microvascular surgery. A great degree of variability was noted in intraoperative and postoperative care of free flap patients. Overall, self-reported free flap survival-rates were relatively high, despite the variability in practice, with the majority of surgeons (74%) reporting flap survival rate of 96-100%. Complication rates requiring return to the operating room were low; all respondents reported <20% overall complications with <10% re-operation rates due to vascular complications. CONCLUSION An increasing number of microvascular-trained otolaryngologists are performing free flaps. Self-reported free flap survival rates are high and complication rates are low, despite significant variability in intraoperative and postoperative practices among otolaryngologists performing microvascular flap reconstruction. By identifying these differences among surgeons, we hope to provide the impetus for further academic dialog and prospective trials.