Assuntina G. Sacco

Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.

Current status of transport-disc-distraction osteogenesis for mandibular reconstruction

Surgical intervention including composite mandibulectomy is the mainstay of treatment for extrication of disease in patients with neoplasms involving the mandible. The associated morbidities and reduction in quality of life after reconstruction of the mandibular defect are dependent on the quality of the reconstruction. Therefore, alternative treatments, such as distraction osteogenesis, could be a viable option to improve patient outcome. The goal of this technology is to restore bony continuity through the use of in-situ bone in an attempt to create an anatomically correct regenerate that is better than bone grafting or revascularised free-tissue transfer. Distraction osteogenesis involves a three-step process in which bone adjacent to the defect is osteotomised and gradually opened (distracted) with the aid of a mechanical device, followed by formation of new bone with subsequent consolidation. Previous work has shown encouraging results regarding the translation of distraction osteogenesis technology from an animal model to human application, with particular success in the unradiated setting. The major challenge surrounding the use of this technology in head and neck oncological reconstruction will be the effect of radiotherapy on the regenerate bone in patients who have previously received or will need radiotherapy as part of their treatment. Although distraction osteogenesis provides an attractive alternative for reconstruction of mandibular defects, large studies of human populations are needed to further assess the use of this technology and its role in the treatment framework for mandibular neoplasms.

Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor–Based Immunotherapy

Purpose: Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response. Experimental Design: We assessed 69 patients with diverse malignancies who received checkpoint inhibitor–based immunotherapy and blood-derived ctDNA NGS testing (54–70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations. Results: Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively; P = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. <6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS >3 had a median PFS of 23 versus 2.3 months (P = 0.0004). Conclusions: Given the association of alteration number on liquid biopsy and checkpoint inhibitor–based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted. Clin Cancer Res; 23(19); 5729–36. ©2017 AACR.

Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer

The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC).

Thoracodorsal artery scapular tip autogenous transplant: vascularized bone with a long pedicle and flexible soft tissue.

OBJECTIVE To demonstrate that the 3 reconstructive advantages of the thoracodorsal artery scapular tip transplant (Tdast), a long pedicle, independently mobile tissue components, and the 3-dimensional nature of the scapular tip, will improve the quality and success of complex reconstructions by avoiding vein grafting, preventing the need for 2 separate transplants, and facilitating bony inset. DESIGN Prospective case series. SETTING Tertiary care academic medical center. PATIENTS Twenty-one patients (male to female ratio, 16:5; mean age, 52 years) underwent reconstruction of the upper, middle, and lower face from 2001 through 2006. Indications for reconstruction were tumor ablation in 11 patients, secondary reconstruction in 4 patients, osteoradionecrosis in 4, and posttraumatic reconstruction in 2. Seventeen patients underwent radiation. INTERVENTIONS All patients underwent harvest of an autogenous transplant of scapular tip bone and latissimus dorsi soft tissue based on the thoracodorsal artery. The mean bone length was 5.2 cm (range, 2.5-9.0 cm), and the mean cutaneous surface area was 68 cm² (range, 20-250 cm²). MAIN OUTCOME MEASURES Reduction of vein grafting, avoidance of 2 transplants, use of the triangular shape of the scapular tip in reconstruction, complications, and shoulder function. RESULTS The success rate of transplantation was 100%. The use of this transplant avoided vein grafting in 16 patients and the need for 2 separate transplants in 11 patients, and the 3-dimensional nature of the scapular tip facilitated inset in 13 patients. In 14 patients, more than 1 of these reconstructive advantages was achieved. In 6 patients, all 3 were accomplished. Eleven patients experienced a complication. The major complication rate was 33%, and the minor complication rate was 33%. The mean Constant-Murley test of shoulder function score was 87 of 100 (range, 74-100). CONCLUSIONS The Tdast is an excellent choice for reconstruction in the head and neck as an alternative to procedures requiring vein grafting and multiple free tissue transplants, or in which the 3-dimensional contour of the scapular tip aids in reconstruction. The complication rate should be assessed in the context of the risk factors of the patient population and the outcome with respect to stable employment, increasing body mass index, and maintenance of shoulder function.

Oropharyngoplasty with template-based reconstruction of oropharynx defects.

OBJECTIVE To determine if oropharyngoplasty using a Gehanno technique of superior constrictor velopharyngoplasty, base of tongue mounding, and primary hypopharyngeal closure in combination with template-based revascularized free tissue transfer is effective for reconstruction of the oropharyngeal defect. DESIGN Prospective case series. SETTING Tertiary care academic medical center. PATIENTS The study population comprised 25 patients (21 men and 4 women; mean age, 55.3 years) presenting from January 1998 to January 2001 with oropharyngeal squamous cell carcinoma. A comparison was performed based on the percentage of resection of the soft palate (group 1, < or =50% palate; group 2, >50% palate). INTERVENTIONS Of the 25 patients, 24 (96%) received radiotherapy. The donor sites were radial forearm for 23 of 25 patients (92%) and lateral arm for 2 of 25 patients (8%). The mean area was 92 cm(2) (range, 25-150 cm(2)), and the mean length of the velopharyngoplasty component of the oropharyngoplasty was 2.15 cm (range, 1-3 cm). MAIN OUTCOME MEASURES Gastrostomy tube dependence, major and minor complications, time to oral intake, speech and swallowing assessment, and quality-of-life assessment. RESULTS Of the 25 patients, 2 (8%) remain gastrostomy dependent; 6 (24%) developed major complications; and 7 (28%) developed minor complications. Speech in both groups 1 and 2 was considered understandable most of the time, with occasional repetition. The group 1 patient with a median assessment score could eat a solid diet without restriction of place or person, whereas the group 2 patient with a median assessment score could eat a soft, moist diet with selected persons in selected places. CONCLUSION Integration of oropharyngoplasty with template-based revascularized free tissue transfer produced speech results that were independent of palate defect size, and swallow function test results were similar to other published reconstructive techniques.

Advanced squamous cell carcinoma of the oropharynx: Efficacy of positron emission tomography and computed tomography for determining primary tumor response during induction chemotherapy

To evaluate the efficacy of fluorine‐18‐fluorodeoxyglucose emission tomography (FDG‐PET) and CT versus endoscopy with biopsy under general anesthesia for estimating tumor volume reduction among patients treated with induction chemotherapy for advanced squamous cell carcinoma (SCC) of the oropharynx.

LATERAL OROMANDIBULAR DEFECT: WHEN IS IT APPROPRIATE TO USE A BRIDGING RECONSTRUCTION PLATE COMBINED WITH A SOFT TISSUE REVASCULARIZED FLAP?

A quasi‐experimental retrospective study was undertaken to evaluate a new concept of free tissue volume restoration combined with bridging reconstruction plate (compartment approach) to reduce plate‐related complication rates.

Chronic Opioid Use Following Surgery for Oral Cavity Cancer

Importance Opioid misuse and overuse has become an epidemic. Chronic opioid use among oral cavity cancer patients after surgery has not been described. Objectives To assess the prevalence of chronic opioid use in patients undergoing surgery for oral cavity cancer, and evaluate possible associated clinical factors; and the association between opioid use and survival. Design, Setting, and Participants For this retrospective cohort study of patients undergoing surgery for oral cavity cancer a consecutive sample of 99 patients between January 1, 2011, and September 30, 2016, were identified through the institutional cancer registry from a single academic center. Exposures Surgery for oral cavity cancer. Main Outcomes and Measures Chronic opioid use, defined as more than 90 days from surgery. Factors associated with chronic opioid use were investigated by univariable and multivariable logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess overall survival and disease-free survival. Results The mean (SD) patient age was 62.6 (14.3) years; 60 patients (60%) were male. Chronic opioid use was observed in 41 patients (41%). On multivariable logistic regression, preoperative opioid use (odds ratio [OR], 5.6; 95% CI, 2.2-14.3), tobacco use (OR, 2.8; 95% CI, 1.0-8.0), and development of persistence, recurrence, or a second primary tumor (OR, 2.8; 95% CI, 1.0-7.4) were associated with chronic opioid use. Among preoperative opioid users, estimated overall survival (hazard ratio [HR], 3.2; 95% CI, 1.4-7.1) was decreased, and chronic opioid use was associated with decreased disease-free survival (HR, 2.7; 95% CI, 1.1-6.6). Conclusions and Relevance In patients undergoing surgery for oral cavity tumors, the prevalence of chronic opioid use was considerable. Preoperative opioid use, tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use after surgery, and both preoperative and chronic opioid use were associated with decreased survival.

Molecularly targeted therapy for the treatment of head and neck cancer: a review of the ErbB family inhibitors.

The majority of patients with head and neck squamous cell carcinoma (HNSCC) present with locally advanced disease, which requires site-specific combinations of surgery, radiation, and chemotherapy. Despite aggressive therapy, survival outcomes remain poor, and treatment-related morbidity is not negligible. For patients with recurrent or metastatic disease, therapeutic options are further limited and prognosis is dismal. With this in mind, molecularly targeted therapy provides a promising approach to optimizing treatment efficacy while minimizing associated toxicity. The ErbB family of receptors (ie, epidermal growth factor receptor [EGFR], ErbB2/human epidermal growth factor receptor [HER]-2, ErbB3/HER3, and ErbB4/HER4) is known to contribute to oncogenic processes, such as cellular proliferation and survival. EGFR, specifically, is upregulated in more than 90% of HNSCC, has been implicated in radiation resistance, and correlates with poorer clinical outcomes. The central role of EGFR in the pathogenesis of HNSCC suggests that inhibition of this pathway represents an attractive treatment strategy. As a result, EGFR inhibition has been extensively studied, with the emergence of two classes of drug therapy: monoclonal antibodies and tyrosine kinase inhibitors. While the monoclonal antibody cetuximab is currently the only US Food and Drug Administration–approved EGFR inhibitor for the treatment of HNSCC, numerous investigational drugs are being evaluated in clinical trials. This paper will review the role of the ErbB family in the pathogenesis of HNSCC, as well as the evidence-based data for the use of ErbB family inhibition in clinical practice.