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Background: We sought to characterize early changes in CD8 + tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial., Methods: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8 + tumor-infiltrating lymphocytes and transcriptomes were assessed., Results: One week after cetuximab, five patients (62.5%) had an increase in CD8 + cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8 + cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways., Conclusions: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: We examined the effect of free tissue neurotization on speech and swallowing outcomes for patients undergoing reconstruction of hemiglossectomy defects with a radial forearm free flap (RFFF)., Methods: A retrospective study was performed in patients with oral cavity squamous cell carcinoma undergoing a hemiglossectomy and reconstruction with a RFFF. Functional outcomes including nutritional mode, range of liquids and solids, and speech understandability were analyzed 1-year post-treatment., Results: Eighty-four patients were included in this analysis, 41 of whom had neurotized flaps (49%). No significant differences in demographic or clinical variables were seen between the neurotized and non-neurotized groups. On multivariate analysis controlling for BMI, flap area, and N-classification, patients with neurotized flaps were significantly more likely to have normal range of liquids and solids and less likely to have a G-tube., Conclusions: Neurotization of RFFF reconstructing hemiglossectomy defects results in decreased G-tube dependence and improved range of liquids and solids., (© 2022 Wiley Periodicals LLC.)

Free tissue transfer from the subscapular system provides a wide array of options for both soft tissue and bony reconstruction. When bone stock is required for head and neck reconstruction, both the lateral scapular border free flap (LSBFF), supplied by the circumflex scapular artery, and the scapular tip free flap (STFF), supplied by the angular artery, are excellent options. Issues with positioning had previously prevented the widespread use of these bony subscapular system flaps. However, through the use of a Spider Limb Positioner, current clinical practice patterns allow for two team approaches in both of these free flaps. The following pictorial essay compares and contrasts the specific positioning and harvesting technique used for both the LSBFF and STFF, while discussing the clinical advantages and drawbacks of each. Both the lateral border scapula and scapular tip free flaps provide excellent bone stock for head and neck reconstruction. By positioning with currently available technology, both of these free flaps can be harvested through a two team approach., (© 2021 Wiley Periodicals LLC.)

Background: Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications., Methods: Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment., Main Outcome: wound complications., Results: Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not., Conclusions: Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy., (© 2021 Wiley Periodicals LLC.)

Background: We sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene-specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA)., Methods: The tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene-specific alteration frequencies were compared (Chi-Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform., Results: Persistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53., Conclusions: Our results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts., (© 2018 Wiley Periodicals, Inc.)

Background: Total laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal., Methods: A prospectively maintained single-institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan-Meier survival curves and hazard ratios (HRs) were calculated., Results: Five-year overall survival (OS) was 49%. Five-year disease-free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation-27 [ACE-27] scale; HR 3.76; 95% confidence interval [CI] 1.56-9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74-4.88)., Conclusion: Severe comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies., (© 2017 Wiley Periodicals, Inc.)

Background: Delayed nonspecific posterior neck pain after pharyngeal instrumentation can be associated with a syndrome of rapidly progressive neurologic embarrassment. We present this cohort to help define the syndrome and aid in early detection., Methods: We conducted a retrospective case series of 6 patients presenting from 2003 to 2012 with a history of laryngeal or hypopharyngeal squamous cell carcinoma (SCC) who underwent radiotherapy (RT) or chemoradiotherapy (CRT) followed by salvage laryngectomy., Results: Posterior neck and upper back pain developed a mean of 27.5 days after instrumentation of the pharynx (reconstruction after laryngectomy or pharyngeal dilation). Myelopathy developed an average of 21.5 days after the onset of posterior neck pain. Five patients required urgent decompression. Three patients developed quadriplegia. The disease-specific mortality was 50%., Conclusion: There is a syndrome of late neurological effects after RT, salvage surgery, and pharyngeal instrumentation that is associated with high morbidity and mortality. © 2016 Wiley Periodicals, Inc. Head Neck 38:1187-1193, 2016., Competing Interests: None, (© 2016 Wiley Periodicals, Inc.)