Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single-institution retrospective study.

BACKGROUND: Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC. METHODS: Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included. Survival was estimated using the Kaplan-Meier method, and Cox regression was used for multivariate logistic regression. RESULTS: Two-year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio [HR] 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil-to-lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02). CONCLUSION: Our retrospective single-institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required.

Trends in Positive Surgical Margins in cT1-T2 Oral Cavity Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate trends in contemporary positive surgical margin incidence in cT1-T2 oral cavity squamous cell carcinoma and to evaluate factors associated with surgical margin status. STUDY DESIGN: Retrospective analysis of large dataset. METHODS: Retrospective analysis of the National Cancer Database. RESULTS: Between 2004 and 2016, 39,818 patients with cT1 or cT2 oral cavity squamous cell carcinoma received primary curative-intent surgery. Positive surgical margins were present in 7.95% of patients, and univariable adjusted probability of positive surgical margins over the study period declined by 1% per year (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-1.0; P = .049). Multivariable regression revealed the annual rate of positive surgical margins declined significantly (OR, 0.95 per year; 95% CI, 0.92-0.97; P < .001). Factors associated with increased odds of positive surgical margins included cT2 disease, subsite, understaged disease, lymphovascular invasion, tumor grade, and positive lymph nodes. Race and socioeconomic status were not associated with surgical margin status. Treatment at an academic center was associated with increased time to definitive surgery (median 35 days IQR 22-50 vs. median 27 days IQR 14-42; P < .001) and a 20% reduction in positive surgical margin rate (OR, 0.80; 95% CI, 0.71-0.90; P < .001). Treatment at high-volume centers was less likely to be associated with positive surgical margins (OR, 0.85; 95% CI, 0.74-0.98; P = .02). CONCLUSION: Surgical subsite, clinical T and N category, presence of lymphovascular invasion, and histologic grade were independent predictors of positive surgical margins. Patients are increasingly being treated at high-volume and academic centers. Overall, the rate of positive surgical margins in cT1-T2 oral cavity squamous cell carcinoma is decreasing. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1962-1970, 2022.

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

Free Flap Elevation Times in Head and Neck Reconstruction Using the Harmonic Scalpel Shears.

Free tissue transfer has become the mainstay of head and neck cancer (HNC) reconstructive surgery. The objective of the study is to examine the efficacy of the Harmonic Scalpel (HS) Shears on free flap elevation time and complication rates after HNC reconstruction compared with traditional electrocautery. A retrospective review of 215 HNC patients undergoing surgical ablation and free flap reconstruction from January 2010 to April 2013 at the University of Alberta Hospital was undertaken. All patients requiring free flap reconstruction with radial forearm free flap or fibula free flap were included. Overall, there was no significant difference demonstrated between the HS and electrocautery groups for free flap elevation time for RFFFs (P = 0.563) or FFFs (P = 0.087). No differences were observed in donor-site complications. The HS is a reliable, safe, and alternative method of free flap elevation in HNC reconstructive surgery.

Bone-impacted fibular free flap: Long-term dental implant success and complications compared to traditional fibular free tissue transfer.

BACKGROUND: The purpose of this study was to compare complications and dental implant success between the bone-impacted fibula free flap (BIFFF) and the traditional fibular free flap used in mandibular and midface reconstruction. METHODS: Retrospective review of all patients undergoing BIFFF or traditional fibular free flap reconstruction from 2001 to 2009 was undertaken. Complications related to the BIFFF and traditional fibular free flap site of reconstruction were compared. Dental implant success rates for each type of flap were compared at 1-year intervals for 5 years. RESULTS: One hundred fourteen patients underwent 81 BIFFFs and 35 traditional fibular free flaps. No significant difference in complications between BIFFF (20.9%) and traditional fibular free flap (25.7%) reconstruction was observed. Logistic regression analysis revealed only the site as a predictor of both single and multiple complications. At 5 years postimplantation, dental implant success rates were 95.5% and 77.1% for BIFFF and traditional fibular free flap, respectively (p = .006). CONCLUSION: BIFFF reconstruction is a novel surgical technique that may improve long-term dental implant success rates with no additional risk of complications. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1783-E1787, 2016.

Factors associated with severe deep neck space infections: targeting multiple fronts.

OBJECTIVES: To determine factors predictive of a severe deep neck space infection (DNSI), defined as those requiring surgery and/or postoperative intensive care unit (ICU) admission. To specifically examine dental practices and socioeconomic factors that may contribute to the development of a DNSI. STUDY DESIGN: Retrospective review. METHODS: This study was conducted at 2 tertiary care academic referral centers from January 2007 to September 2011. The study was composed of 2 arms: a prospective questionnaire and data collection to identify modifiable risk factors such as dental practices and socioeconomic considerations for a DNSI, and a retrospective review of deep neck space infections to identify commonly associated risk factors predictive of a severe DNSI, requiring surgery and/or postoperative ICU admission. RESULTS: 233 patients were reviewed retrospectively and 25 patients prospectively. Patients with a low level of education (p = 0.03), those living greater than 1 hour from a tertiary care center (p = 0.002), those that have tonsils (p = 0.03), and those with Streptococcus infections (p = 0.03) have an increase risk of developing a severe DNSI. Patients that were smokers (p = 0.02) or had diabetes (p = 0.02), and those that presented with airway compromise (p = 0.03) were more likely to have a prolonged hospital stay. CONCLUSIONS: Factors predictive of severe DNSIs are Streptococcus infections, the presence of tonsils, education level, and geographic location.

Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing due to fundamental changes in oncogenesis related to effects of the human papilomavirus (HPV). Virally-mediated tumours behave and respond to treatment differently than their classic, carcinogenically-mediated counterparts despite similar stage and grade of disease. This difference in behaviour has lead to investigation of etiologies of OPSCC at the molecular level. OBJECTIVE: This study was designed to identify biomarker profiles predictive of locoregional and distant metastases and recurrence in OPSCC. METHODS: Cross-sectional study of a prospectively-collected oropharyngeal tumour database was undertaken. All patients with OPSCC presenting to the University of Alberta Hospital from 2002-2009 were included in the study. Data collection from the Alberta Cancer Registry, including demographics, nodal status, distant metastases, treatment, recurrence, and survival, was undertaken. Tissue micro-arrays (TMAs) were constructed for each tumour specimen using triplicate cores (0.6mm) of formalin-fixed, paraffin-embedded (FFPE) pre-treatment tumour tissue. TMAs were processed using immunohistochemistry for p16, EGFR, Ki67, p53, and Bcl-XL. Positivity for each biomarker was determined using quantified AQUAnalysis ® scores on histoplots. Multivariate statistics were utilized to assess the relationship between each biomarker and locoregional and distant metastases, as well as recurrence-free survival (RFS). RESULTS: High expression of p16 (p=0.000) and Bcl-XL (p=0.039) independently demonstrated a significant association with nodal disease at presentation. Kaplan-Meier analysis demonstrated improved RFS in patients with high p16 and decreased RFS in patients with high p53 expression. Cox regression analysis supported p16 as an independent prognosticator for improved RFS. p53 demonstrated an association with recurrence, but when compared to p16 status, nodal status, and staging, was not an independent predictor of recurrence. CONCLUSIONS: Biomarker profiling using p16, Bcl-xL, and p53 may be useful in prognostication and treatment planning in patients with OPSCC.

Double free-flap reconstruction: indications, challenges, and prospective functional outcomes.

OBJECTIVE: To investigate the increasing use of double free flaps in the reconstruction of large head and neck defects. DESIGN: A 5-year retrospective medical record review in a large tertiary care head and neck oncology program. Prospectively collected functional data were also analyzed. SETTING: Academic research. PATIENTS: A consecutive series of 35 patients (24 men and 11 women; mean age, 57.7 years). MAIN OUTCOME MEASURES: The use of double free flaps in the reconstruction of large head and neck defects and prospective functional outcomes. RESULTS: The most common indication for surgery (n = 25 [71.4%]) was squamous cell carcinoma. The most common double free-flap combination (n = 22 [62.9%]) included an osteocutaneous fibular free flap with a fasciocutaneous radial forearm free flap. Objective evaluation by naive listeners demonstrated a mean single-word intelligibility score of 66.2% and a mean sentence intelligibility score of 84.8% in this group of patients. Modified barium swallow study results revealed no evidence of laryngeal penetration for swallowing liquid consistencies in 21 patients (60.0%), pudding consistencies in 30 patients (85.7%), and cookie consistencies in 32 patients (91.4%). CONCLUSIONS: With proper patient selection and planning and the use of 2 surgical teams, the length of surgery and complication rates are not significantly increased in double free-flap reconstruction. Furthermore, by using 2 free flaps, the best osseous and soft-tissue elements may be independently selected, yielding appropriate tissue characteristics for ideal defect reconstruction.