The Role of ctDNA and Liquid Biopsy in the Diagnosis and Monitoring of Head and Neck Cancer: Towards Precision Medicine.

Recent data have shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. The monitoring of biomarkers for head and neck cancer via liquid biopsy, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Radiotherapy vs Surgery for Survival and Locoregional Control of Head and Neck Extramedullary Plasmacytoma: A Systematic Review and Meta-Analysis.

Importance: There are significant gaps in the literature pertaining to the locoregional control and survival rates of extramedullary plasmacytoma (EMP) with respect to various treatment approaches. Objective: To systematically evaluate the differences in radiotherapy and surgical outcomes in EMP. Data Sources: Databases including PubMed, Scopus, Web of Science, Embase, and ScienceDirect were systematically searched from their inception up to November 2023. Study Selection: Articles reporting radiotherapy and surgical outcomes of head and neck EMP were included. Data Extraction and Synthesis: A random-effects model for meta-analysis was used to obtain pooled estimates and calculate hazard ratios for survival and odds ratios for recurrence and progression of EMP. Main Outcomes and Measures: Survival, tumor control, and progression rates to multiple myeloma (MM) between radiation therapy and surgery for EMP of the head and neck. Results: Of 742 included patients from 12 studies, 527 (71.0%) were male, and the median (IQR) age was 59.1 (53-62) years. A total of 505 patients (68.1%) received radiotherapy only, while 237 (31.9%) underwent surgery-only treatment for EMP. All included patients had an initial diagnosis of EMP without MM. Comparable trends were observed in overall survival and disease-free survival (DFS) rates at 2, 3, 5, and 10 years between patients with EMP treated with radiotherapy only and surgery only. Notably, there were no significant differences in recurrence rate (odds ratio, 0.65; 95% CI, 0.20-2.06) between radiotherapy-only and surgery-only treatment. However, radiotherapy-only treatment of EMP was associated with decreased odds of progression to MM compared with surgery (odds ratio, 0.4; 95% CI, 0.1-0.9). Sensitivity analysis revealed that the radiotherapy-only population had significantly better 5-year DFS (hazard ratio, 0.55; 95% CI, 0.31-0.96) compared with surgery-only treatment. Conclusions and Relevance: This systematic review and meta-analysis provides evidence that patients with EMP receiving radiotherapy had significantly lower chances of progression to MM compared with surgery-only therapy. Additionally, radiotherapy had better 5-year DFS outcomes compared with surgery. Comparable outcomes in terms of overall survival rates, recurrence, and mortality rates were noted between radiotherapy-only and surgery-only EMP treatment groups.

Survival Outcomes of Transoral Microsurgery in T3/T4a Laryngeal Tumors: Systematic Review and Meta-Analysis.

OBJECTIVE: To critically evaluate oncological and functional outcomes following transoral laser microsurgery (TLM) in patients with T3/T4a glottic and supraglottic squamous cell carcinoma (SCC). DATA SOURCES: A comprehensive search of five major databases-PubMed, Embase, Scopus, ScienceDirect, and Web of Science-was conducted using a combination of relevant keywords and MeSH terms. REVIEW METHODS: Systematic review and meta-analysis of odds ratio (OR), hazards ratio (HR), and proportion, focusing on oncological and functional outcomes of TLM in advanced T3/T4a glottic and supraglottic tumors. A random-effects meta-analysis model was employed. RESULTS: The review incorporated 29 cohort studies, representing a total of 1,897 patients undergoing TLM for T3/T4a glottic and supraglottic SCC. The cumulative 5-year disease-free survival (DFS) rate for T3 glottic and supraglottic tumors was 44.4% (95% CI: 47-66%) and 62.8% (95% CI: 63-81%), while the 5-year DFS for T4 glottic and supraglottic tumors was 41.1% (95% CI: 33.4-49.2%) and 32.9% (95% CI: 19.3-50.1%), respectively. T3 glottic tumors exhibited a 2.5-fold significantly higher odds of local recurrence post-TLM compared to their T3 supraglottic tumors (95% CI: 1.6-3.9, p < 0.0001). Laryngeal preservation rates for T3glottic and supraglottic tumors were 68.9% (95% CI: 48.7-83.8%) and 88.4% (95% CI: 79.4-93.8%), respectively. Both groups showed comparable rates of tracheostomy (p = 0.48) and gastrostomy performed (p = 0.17). CONCLUSIONS: This meta-analysis suggests that TLM is a viable larynx preservation approach in select patients with T3/T4a glottic and supraglottic tumors. However, glottic tumors may have less favorable outcomes after TLM compared to those with advanced supraglottic tumors. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024 Laryngoscope, 2024.

Efficacy and safety of proton therapy versus intensity-modulated radiation therapy in the treatment of head and neck tumors: A systematic review and meta-analysis.

To comprehensively evaluate the therapeutic efficacy and safety when utilizing proton therapy (PT) versus intensity-modulated radiation therapy (IMRT) in head and neck cancer patients. Pubmed, ScienceDirect, Embase, Scopus, and Web of Science were systematically searched for studies on comparative PT and IMRT outcomes. We performed a random effect model meta-analysis to estimate the hazard ratio (HR) and odds ratio (OR) for efficacy and safety outcome variables between PT and IMRT. From 641 identified articles, 11 studies met the inclusion criteria, comprising 3087 patients (606 treated with PT and 2481 with IMRT). On toxicity analysis, PT is associated with decreased acute grade 1 nausea (OR = 0.34, 95% CI: 0.13-0.84, p = 0.02) compared to IMRT. In grade 2 toxicity, PT showed significant advantages over IMRT in mucositis (OR = 0.44, p < 0.0001), dysgeusia (OR = 0.35, p = 0.02), dysphagia (OR = 0.36, p < 0.0001), fatigue (OR = 0.29, p = 0.001), pain (OR = 0.34, p = 0.01), and weight loss (OR = 0.54, p = 0.02). Proton therapy also exhibited increased safety in grade 3 dysphagia incidence (OR = 0.44, p < 0.0001) compared to IMRT. PT demonstrated improved overall survival (OS) compared to IMRT across multiple time points: 1-year OS (HR = 0.43, p = 0.02), 2-year OS (HR = 0.44, p < 0.0001), and 5-year OS (HR = 0.78, p = 0.004). In terms of disease-free survival (DFS), PT also showed improved outcomes at 2-year DFS (HR = 0.65, p = 0.03) and 5-year DFS (HR = 0.81, p = 0.03). Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT. The data also showed better safety outcomes in PT patients, particularly when involving grade 2 acute toxicity events.

Outcomes of internal mammary artery perforator flap in head and neck reconstruction: A systematic review.

This study aims to evaluate the functional and prognostic outcomes associated with the internal mammary artery perforator (IMAP) flap in various head and neck defect repairs, given the current lack of clarity on its effectiveness. We performed a systematic review of various databases: PubMed, Embase, Scopus, Web of Science, and ScienceDirect using keywords such as "Internal mammary artery perforator flap" and "IMAP." Screening and data extractions were performed by two individual reviewers. Articles were considered eligible if they included sufficient information on IMAP flap features, their applications in the head and neck, and outcomes. From 264 articles analyzed, 24 studies were included for qualitative analysis. Out of which, 125 patients who received internal mammary artery perforator flaps were included. Most of the patients, 103 (88%), received pedicled IMAP flaps, and 22 (12%) received IMAP free flaps. The second internal mammary artery (IMA) was favored as the single perforator (81.5%), with the combination of the first and second IMA being the primary choice for dual perforators (92.5%). IMAP flaps were predominantly single perforator flaps (65%), with 35% being dual perforator flaps. Among various applications, IMAP flaps are commonly employed in the reconstruction of neck defects (25.5%), pharyngocutaneous fistula repair (20.8%), and burn scar contracture restoration (8%). Only seven (5.6%) patients had flap complications, including venous congestion (1.6%), partial necrosis (1.6%), complete necrosis (1.6%), and incision dehiscence (0.8%). Donor sites were predominantly closed by the primary closure (92%). 3.2% of donor sites had minor complications. The average follow-up was 12.6 (IQR: 6-18) months. This systematic review highlights the effectiveness and safety of IMAP flaps in head and neck reconstruction, with positive outcomes and minimal complications.

Risk Factors for Complications in Patients Undergoing Temporal Bone Resection and Neck Dissection: Insights From a National Database.

BACKGROUND: Temporal bone resection (TBR) with or without neck dissection (ND) is performed for otologic malignancies with occult or clinical cervical lymph node metastases. To date, characterization of post-operative complications in single institution case series may be non-representative of real-world outcomes. Here, we used data from the National Inpatient Sample (NIS) to comprehensively assess the complications encountered, their frequencies, and to identify underlying risk factors to improve future outcomes. METHODS: The population was patients undergoing TBR and ND derived from the NIS between the years of 2017 and 2019. We utilized ICD-10 diagnosis codes to identify patients with post-operative complications, those discharged to non-home facilities (DNHF), and those with increased length of stay (LOS). Multivariable regression was performed to identify significant variables related to the above outcomes. RESULTS: Ninety of 277 patients that underwent LTBR with ND had postoperative complications. Wound complications were the most frequent complication, occurring in 11 (4%) of patients, followed by CSF leak (n = 6; 2.2%), with acute respiratory failure being the most common medical complication (n = 4; 1.4%). Sixteen percent (45/277) were discharged to a facility besides home. Dementia (OR = 7.96; CI95 3.62-17.48), anemia (OR = 2.39; CI95 1.15-4.99), congestive heart failure (OR = 5.31; CI95 1.82-15.45), COPD (OR = 3.70; CI95 1.35-10.16), and history of prior stroke (OR = 8.50; CI95 1.55-46.68) increased the odds of DNHF. When evaluating LOS (median = 5 days, IQR = 1, 9), anemia (OR = 5.49; CI95 2.86-10.52), and Medicaid insurance (OR = 3.07; CI95 1.06-10.52) were found to increase the LOS. CONCLUSIONS: The vast majority of patients undergoing LTBR with ND have no complications and are discharged within a week. Liver disease is a risk factor for medical complications and increased charges. Patients with dementia or a prior stroke are at risk for DNHF, and those with prior anemia are at risk for a wound complication. LAY SUMMARY: This study identified factors related to worse post-operative outcomes in patients undergoing temporal bone resection and neck dissection. Although safe for most patients, an existing diagnosis of liver disease, stroke, dementia, and anemia specifically are at risk for developing negative outcomes. LEVEL OF EVIDENCE: 3.

Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment.

OBJECTIVE: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. STUDY DESIGN: Retrospective Single Institutional Study. SETTING: University Hospital Setting. METHODS: Twenty-nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor-informed, multiplex polymerase chain reaction (PCR) next-generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence-free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV). RESULTS: The median age of patients was 65 years (interquartile range: 56-69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56-63.3, P = .015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV. CONCLUSION: Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret.

Sexual history of patients with human papillomavirus positive and negative oropharyngeal cancer: A systematic review and meta-analysis.

BACKGROUND: Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC). METHODS: In this meta-analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI). RESULTS: A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0-97.0 vs. 74.5%, 95% CI: 50.6-98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5-35.4 vs. 7.2 partners, 95% CI: 1.0-13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4-29.0 vs. 8.8%, 95% CI: 4.7-12.8, p = 0.0001). CONCLUSIONS: Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history.

Inducible Keratinocyte Specific FGFR2 Deficiency Inhibits UVB-Induced Signaling, Proliferation, Inflammation, and Skin Carcinogenesis.

A potential role for fibroblast growth factor receptor 2 (FGFR2) in cutaneous squamous cell carcinoma (cSCC) has been reported. To demonstrate the specific role of FGFR2 in UVB-induced skin carcinogenesis and development of cSCC, we generated a keratinocyte specific, tamoxifen inducible mouse model of FGFR2 deficiency. In this mouse model, topical application of 4-hydroxy tamoxifen led to the induction of Cre recombinase to delete FGFR2 in epidermal keratinocytes of both male and female transgenic mice. Analysis of epidermal protein lysates isolated from FGFR2 deficient mice exposed to UVB showed significant reductions of phospho-FGFR (pFGFR; Y653/654) and phospho-fibroblast growth factor receptor substrate 2α as well as downstream effectors of mTORC1 signaling. Phosphorylation of signal transducer and activators of transcription 1/3 was significantly reduced as well as levels of IRF-1, DUSP6, early growth response 1, and PD-L1 compared to the control groups. Keratinocyte-specific ablation of FGFR2 also significantly inhibited epidermal hyperproliferation, hyperplasia, and inflammation after exposure to UVB. Finally, keratinocyte-specific deletion of FGFR2 significantly inhibited UVB-induced cSCC formation. Collectively, the current data demonstrate an important role of FGFR2 in UVB-induced oncogenic signaling as well as development of cSCC. In addition, the current preclinical findings suggest that inhibition of FGFR2 signaling may provide a previously unreported strategy to prevent and/or treat UVB-induced cSCC.

Impact of Dementia on the Postoperative Outcomes in Patients Undergoing Surgery for Head and Neck Cancers: A National Study.

BACKGROUND: Dementia, a growing concern among the elderly, has an increased poor postoperative outcome that goes unrecognized by many. Our study aims to establish if dementia plays a role in the outcomes of head and neck cancer patients that undergo resections. METHODS: We queried the National Inpatient Sample (NIS) database from 2016 to 2019 with a primary diagnosis of head and neck cancer who underwent surgical resection. Outcomes analyzed include postoperative delirium, ICU stay, complications, length of stay, and non-routine discharge. RESULTS: A total of 77095 patients were included, of which 1140 patients had dementia. The mean age of the patients with dementia was 77.5 years (±9.1) versus 63.2 years (±12.1) with no dementia. Dementia patients had a higher non-home discharge rate (77.2% vs 46.8%, p = <0.001), extended length of stay (10.9 days ±14.7 vs 7.9 days ±8.8), postoperative delirium (15.4% vs 1.5%, p = <0.001), and longer ICU stay (8.3% vs 5.8%) as compared with patients with no dementia. A higher number of patients with Dementia were placed in long-term facilities (53.5% vs 14.6%) postoperatively. More dementia patients (7.9% vs 0.9%) were transferred in from another health care facility for surgery. Dementia was associated with higher odds of delirium (OR, 6.36; 95% CI, 5.2-7.77), non-routine discharge (OR, 2.05; 95% CI, 1.76-2.3), ventilation (OR, 0.8; 95% CI, 0.6-1.05), and length of stay (estimate 3.01, 95% CI, 1.84-4.184). CONCLUSION: Preoperative dementia significantly impacts postoperative delirium, non-home discharge, and extended length of stay in head and neck cancer patients undergoing surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1258-1264, 2024.

Editorial: Special Issue on the Epidemiology of Human Papilloma Virus-Associated Oropharyngeal Squamous Cell Carcinoma.

In this Special Issue of Cancers, the role of oncogenic human papilloma virus (HPV) with oropharyngeal squamous cell carcinoma is explored […].

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Regional pedicled flap salvage options for large head and neck defects: The old, the new, and the forgotten.

Objectives: The objective of this article is to review options for regional pedicled reconstruction for large head and neck defects in a salvage setting. Methods: Relevant regional pedicled flaps were identified and reviewed. Expert opinion and supporting literature were used to summarize and describe the available options. Results: Specific regional pedicled flap options are presented including the pectoralis major flap, deltopectoral flap, supraclavicular flap, submental flap, latissimus flap, and trapezius flap. Conclusions: Regional pedicled flaps are useful options in a salvage setting even for large defects and should be in the armamentarium of any reconstructive head and neck surgeon. Each flap option carries specific characteristics and considerations.

Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).

TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50-60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway. Here, we investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models. Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines. Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.

A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.

PURPOSE: Investigate whether adjuvant everolimus, an mTOR inhibitor, improves progression-free survival (PFS) in advanced-stage head and neck squamous cell carcinoma (HNSCC) and provide outcomes related to correlative biological factors associated with disease control. PATIENTS AND METHODS: This was a prospective, randomized, double-blind phase II trial of patients with advanced-stage HNSCC from 13 institutions who were confirmed disease-free post-definitive therapy and enrolled between December 2010 and March 2015. Patients received adjuvant everolimus or placebo daily (10 mg, oral) for a maximum of 1 year. p16 IHC as a surrogate marker for human papillomavirus infection and whole-exome sequencing were performed. Cox proportional hazard models estimated hazard rates. Log-rank tests evaluated differences in survival. The primary endpoint was PFS. Secondary endpoints and objectives included overall survival (OS) and toxicity assessment. RESULTS: 52 patients [median (range) age, 58 (37-76) years; 43 men (83%), 9 women (17%)] were randomized to placebo (n = 24) or everolimus (n = 28). PFS favored everolimus, but was not significant [log-rank P = 0.093; HR = 0.44; 95% confidence interval (CI), 0.17-1.17]. There was no difference in OS (P = 0.29; HR = 0.57; 95% CI, 0.20-16.2). Everolimus resulted in significant improvement in PFS for p16-negative patients (n = 31; P = 0.031; HR = 0.26; 95% CI, 0.07-0.97), although subgroup analysis showed no difference for p16-positive patients (n = 21; P = 0.93). Further, PFS was significantly higher in TP53-mutated (TP53mut) patients treated with everolimus compared with placebo (log-rank P = 0.027; HR = 0.24; 95% CI, 0.06-0.95). No treatment difference was seen in patients with TP53 wild-type tumors (P = 0.79). CONCLUSIONS: p16-negative and TP53mut patients may benefit from adjuvant treatment with everolimus.

Assessment of Facial Injury by "Slock" in Incarcerated Patients.

A "slock" is a padlock in a sock used as a weapon in correctional facilities to induce trauma. This assessment examined the prevalence, pattern, and degree of slock- and padlock-induced facial fractures. This quality assessment initiative was performed through retrospective analysis of 435 incarcerated patients treated surgically for facial fractures at an academic medical center from 2011 to 2019. Fifty-seven patients (16%) described injury from a padlock, of whom 23 (6%) specified a slock. The prevalence of padlock-induced facial fractures doubled from 2012 to 2017. Padlock-induced facial fractures were determined to be more complex than those by a fist (p < .001). These findings support reducing the facial trauma in Louisiana correctional facilities by removing access to padlocks.

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study

Abstract Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy (p =0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p <0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.