Steven M. Sperry

Supracricoid Partial Laryngectomy for Primary and Recurrent Laryngeal Cancer

IMPORTANCE Supracricoid partial laryngectomy (SCPL) is an essential technique in the armamentarium of modern laryngeal organ preservation surgery. OBJECTIVE, DESIGN, SETTING: Retrospective case series to review the oncologic outcomes following SCPL in a large US-based cohort treated by a single surgeon in a tertiary-care university hospital. PARTICIPANTS A total of 96 consecutive patients with primary or recurrent squamous cell carcinoma of the larynx undergoing SCPL from 1992 to 2010. INTERVENTIONS Supracricoid partial laryngectomy surgery. MAIN OUTCOMES AND MEASURES Five-year local control and laryngeal preservation, using the Kaplan-Meier method. RESULTS There were 54 primary laryngeal carcinomas and 42 previously treated with radiation to the larynx; 23% were supraglottic or transglottic tumors (n = 22). The overall 5-year local control rate for the series was 94%. For T2 and T3 primary tumors, the 5-year local control was 100% and 96%, respectively. In patients previously treated with radiation, the 5-year local control was 89%, with an 89% laryngeal preservation rate. Among stage III or IV primary laryngeal tumors for which concurrent chemoradiation was a treatment alternative, the 5-year local and locoregional control was 96% and 83%, respectively, and the 5-year larynx preservation was 91%. Ultimate local control was achieved for all patients in the series. A significant postoperative complication occurred in 19% (n = 18) and 1 anesthesia-related perioperative death occurred. No total laryngectomies were performed for laryngeal dysfunction. CONCLUSIONS AND RELEVANCE This series demonstrates excellent local control for both primary and recurrent laryngeal cancers, with functional larynx preservation. In appropriately staged and selected patients with T2 or T3 primary laryngeal cancer or laryngeal cancer following prior radiation treatment, SCPL should be considered as a treatment alternative to non-surgical treatment or total laryngectomy.

The University of Pennsylvania curriculum for training otorhinolaryngology residents in transoral robotic surgery.

Purpose: To define a curriculum for the development of robotic surgical skills in otorhinolaryngology residency training. Methods: A systematic review of the current literature on robotic surgery training was performed. Based on prior reports in other specialties, a curriculum for otorhinolaryngology residents was created that progresses through several modules, including didactics, inanimate skills laboratory, and operative experience. Results: The curriculum for residents in otorhinolaryngology was designed as follows: didactics include an overview of the robotic device and instruments, a tutorial in basic controls and function, and a room setup and positioning. The anatomy and steps of transoral procedures are taught through books, videos, operative observations, and cadaver dissections. Skills are developed with a virtual reality robotic simulator and robotics labs. The operative experience progresses from case observation to bedside assistant to console surgeon. The role of the console surgeon progresses in a stepwise fashion, and the procedures of radical tonsillectomy, supraglottic partial laryngectomy, and base of tongue resection have been organized as a series of steps. Conclusion: A structured curriculum for training residents in transoral robotic surgery was developed. This training is important for otorhinolaryngology residents to acquire the knowledge and skills to perform robotic surgery safely.

EGFR Inhibition Promotes an Aggressive Invasion Pattern Mediated by Mesenchymal-like Tumor Cells within Squamous Cell Carcinomas

Squamous cell carcinomas (SCC) with an infiltrative invasion pattern carry a higher risk of treatment failure. Such infiltrative invasion may be mediated by a mesenchymal-like subpopulation of malignant cells that we have previously shown to arise from epithelial–mesenchymal transition (EMT) and resist epidermal growth factor receptor (EGFR) targeting. Here, we show that SCCs with infiltrative, high-risk invasion patterns contain abundant mesenchymal-like cells, which are rare in tumors with low-risk patterns. This cellular heterogeneity was modeled accurately in three-dimensional culture using collagen-embedded SCC spheroids, which revealed distinct invasive fronts created by collective migration of E-cadherin–positive cells versus infiltrative migration of individual mesenchymal-like cells. Because EGFR expression by mesenchymal-like cells was diminished in the spheroid model and in human SCCs, we hypothesized that SCCs shift toward infiltrative invasion mediated by this subpopulation during anti-EGFR therapy. Anti-EGFR treatment of spheroids using erlotinib or cetuximab enhanced infiltrative invasion by targeting collective migration by E-cadherin–positive cells while sparing mesenchymal-like cells; by contrast, spheroid invasion in absence of mesenchymal-like cells was abrogated by erlotinib. Similarly, cetuximab treatment of xenografts containing mesenchymal-like cells created an infiltrative invasive front composed of this subpopulation, whereas no such shift was observed upon treating xenografts lacking these cells. These results implicate mesenchymal-like SCC cells as key mediators of the infiltrative invasion seen in tumors with locally aggressive behavior. They further show that EGFR inhibition can promote an infiltrative invasion front composed of mesenchymal-like cells preferentially in tumors where they are abundant before therapy. Mol Cancer Ther; 12(10); 2176–86. ©2013 AACR.

Molecular imaging assisted surgery improves survival in a murine head and neck cancer model.

Surgery plays an important role in the treatment of head and neck cancer (HNC), and surgical margin status is a key prognostic factor. Molecular imaging (MI) can be applied to identify tumor extensions intraoperatively. We applied this technique in a murine HNC model to determine whether it improves outcomes from surgical intervention. An orthotopic murine model with HNC was established with SCC VII cells expressing a green fluorescent protein. To determine the diagnostic accuracy of MI, 20 murine models undergoing standard surgical resection were assessed with MI to identify residual tumor, which was compared to histology as the gold standard. Then, to assess the effect of MI as a therapeutic intervention for survival, 65 mice were randomly divided into standard surgical resection, MI‐assisted surgical resection, and control groups. In the MI‐assisted surgery group, residual signals identified by MI underwent further tissue excision to eliminate the signal positivity. In diagnostic accuracy analysis, sensitivity and specificity of intraoperative MI in the HNC murine model were 86% and 100%, respectively. The mice undergoing MI‐assisted surgery showed a significantly improved 60‐day survival rate compared to standard surgery, 37% versus 5%, respectively. Intraoperative MI guidance is a promising technique in oncologic surgery, which could increase the efficacy of tumor resection and the survival of patients with HNC. The hurdles in applying this technique in clinical practice are still considerable, and further research and development is warranted.

Risk and Survival of Patients with Head and Neck Cutaneous Melanoma: National Perspective

Objective: Head and neck cutaneous melanoma represents a distinct entity of skin cancer. We aim to examine management and survival of patients with head and neck cutaneous melanoma. Methods: A retrospective cohort study utilizing the National Cancer Database, 2004-2012. Results: A total of 20,322 (21.2%) head and neck melanomas and 75,547 (78.8%) melanomas of other sites were included. The median follow-up time of head and neck melanoma was 41.6 months (interquartile range: 22.9-68.2 months). Patients with melanoma of the head and neck were more likely to be ≥65 years old, male, and/or white (p < 0.001 each). Positive surgical margin was more prevalent in head and neck melanoma [OR: 2.19, 95% CI: (2.03, 2.37)], and was associated with a lower survival [HR: 1.41, 95% CI: (1.28, 1.57)]. High positive lymph node ratio was associated with a lower survival [HR: 2.00, 95% CI: (1.13, 3.57)]. Adjuvant immunotherapy was associated with an improved survival [HR: 0.67, 95% CI: (0.57, 0.80)]. Conclusion: Head and neck cutaneous melanoma is associated with certain demographics. Surgical margin status, lymph node ratio, and immunotherapy are independently associated with overall survival.

Longitudinal Perioperative Pain Assessment in Head and Neck Cancer Surgery.

Objective: To evaluate perioperative pain in patients undergoing major head and neck cancer surgery and identify associations between preoperative and postoperative pain characteristics. Methods: Patients undergoing head and neck surgery with regional/free tissue transfer were enrolled. Preoperative pain and validated screens for symptoms (neuropathic pain, anxiety, depression, fibromyalgia) were assessed. Postoperatively, patients completed a pain diary for 4 weeks. Results: Twenty-seven patients were enrolled. Seventy-eight percent had pain prior to surgery, and for 38%, the pain had neuropathic characteristics. Thirteen patients (48%) completed at least 2 weeks of the postoperative pain diary. Patients with moderate/severe preoperative pain report significantly greater pain scores postoperatively, though daily pain decreased at a similar linear rate for all patients. Patients with more severe preoperative pain consumed greater amounts of opioids postoperatively, and this correlated with daily postoperative pain scores. Patients who screened positive for neuropathic pain also reported worse postoperative pain. Conclusion: Longitudinal perioperative pain assessment in head and neck patients undergoing surgery suggests that patients with worse preoperative pain continue to endorse worse pain postoperatively and require more narcotics. Patients with preoperative neuropathic pain also report poor pain control postoperatively, suggesting an opportunity to identify these patients and intervene with empiric neuropathic pain treatment.

Comparison between Organ Preservation Surgery and Radiation in Early Supraglottic Carcinoma Is Limited by Bias.

We read with interest the article by Arshad et al comparing survival for early supraglottic cancer between definitive radiation and organ preservation surgery (OPS) using the Survival, Epidemiology, and End Results (SEER) database. The authors report significantly improved disease-specific survival (DSS) for stage I and II supraglottic cancers treated with OPS + neck dissection (ND) vs radiation, with 5-year DSS for stage II patients of 86% vs 60% (hazard ratio, 0.31; P < .001), respectively. This result is remarkable and would have great importance for management decisions in early supraglottic cancer, if true. However, we are concerned that the comparison is made between dissimilar groups of patients in relation to neck metastases and that the subsequent bias is not adequately taken into account in the interpretation of the results. Based on the methods described, the authors excluded from the analysis all patients with node-positive (N+) disease. Since in the SEER database, staging represents a “best stage,” taking all available clinical and pathologic information into account, the primary-radiation group in this study was clinically N–, and the OPS + ND group was pathologically N–. The radiation group would have included patients with occult nodal metastases, but the OPS + ND group would have excluded them. Based on the reported rate for occult metastases for T1 and T2 supraglottic cancer identified by elective neck dissection, we would expect that 30% of the patients in the radiation group had occult nodal metastases. Since the presence of nodal metastases is a powerful negative prognostic factor for survival and signifies a more aggressive behavior of the disease, the exclusion of these patients from the OPS + ND group would be expected to have a significant positive effect on the survival outcome and is a significant source of bias in the study. We appreciate the role that epidemiologic studies such as this can have in provoking further investigation, but the biased results reported by Arshad et al are unlikely to lead to a useful hypothesis and should not be used to guide clinical decision making.

Contents Vol. 76, 2014

R.L. Alford, Houston, Tex. M. Anniko, Uppsala Y.A. Bayazit, Ankara H.H. Birdsall, Houston, Tex. P.J. Bradley, Nottingham J. Califano, Baltimore, Md. P.F. Castellanos, Bimingham, Ala. C. Cernea, São Paulo F.-L. Chi, Shanghai A. Chiu, Tucson, Ariz. N. Cohen, Philadelphia, Pa. M.D. Eisen, Hartford, Conn. L.M. Elden, Philadelphia, Pa. E. Ferekidis, Athens A. Ferlito, Udine R.L. Ferris, Pittsburgh, Pa. L.L. Gleich, Cincinnati, Ohio D.-M. Han, Beijing J.P. Harris, San Diego, Calif. R. Häusler, Bern I. Hochmair, Innsbruck K. Hörmann, Mannheim W. Hosemann, Greifswald K.-B. Hüttenbrink, Köln S. Iurato, Bari A. Kakigi, Tokyo B.N. Landis, Geneva T. Linder, Luzern S. Malekzadeh, Washington, D.C. W.J. Mann, Mainz G. Marioni, Padova J.N. Palmer, Philadelphia, Pa. R. Probst, Zürich A. Rinaldo, Udine R.J. Ruben, Bronx, N.Y. I. Salahuddin, Karachi A. Schrott-Fischer, Innsbruck A. Shiotani, Saitama T.N. Teknos, Columbus, Ohio K. Tomoda, Osaka R.P. Tufano, Baltimore, Md. R.T. Younis, Miami, Fla. P. Zbären, Bern Journal for Oto-Rhino-Laryngology, Head and Neck Sugery