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.

Impact of Obesity on Timing of Tracheotomy: A Multi-institutional Retrospective Study.

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

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.

Predictors of Unplanned Reoperation after Gender-affirming Mastectomy: An Analysis of the NSQIP Database.

Background: Gender-affirming mastectomy (GAM) is a gender-affirmation surgery designed to remove or reduce breast tissue, with or without nipple reconstruction. GAM is the most commonly performed gender-affirmation surgery and risk factors associated with unplanned return to the operating room and reoperation continue to be investigated. This is the largest study of transgender and nonbinary patients undergoing GAM to determine predictors of unplanned reoperation. Methods: The National Surgical Quality Improvement Program database was queried for patients undergoing GAM from 2012 to 2020. The primary outcome was the incidence of unplanned reoperation within 30 days postoperatively. The secondary outcome was the indication for unplanned reoperation within this period. Descriptive statistics were calculated. Bivariate analysis and multivariate logistic regression were performed to determine significant predictors of reoperation after GAM. Results: A total of 2316 patients underwent GAM, of whom 2.2% (n = 51) underwent unplanned reoperation of the chest. The most common indication for unplanned reoperation was hematoma (n = 41, 71.9%) followed by abscess (n = 5, 8.8%). Significant predictors of reoperation were corticosteroid use [adjusted odds ratio (aOR) 95% confidence interval (CI) 5.07 (1.07-23.89)] and diabetes [aOR (CI) 10.98 (3.0-40.33)]. Hispanic/Latinx ethnicity [aOR (CI) 3.19 (1.22-8.33)] and corticosteroid use [aOR (CI) 6.81 (1.45-31.98)] were significant predictors of unplanned reoperation for hematoma evacuation after GAM. Conclusions: Diabetes mellitus and corticosteroid use were associated with unplanned reoperation after GAM. Ethnic correlations remain to be better elucidated as well as the effect of intersectionality. These findings can be used to guide patient selection and surgical decision-making.

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.

Gender Affirming Facial Surgery-Anatomy and Procedures for Facial Masculinization.

For some patients, feminine facial features may cause significant gender dysphoria. Multiple nonsurgical and surgical techniques exist to masculinize facial features. Nonsurgical techniques include testosterone supplementation and dermal fillers. Surgical techniques include soft tissue manipulation, synthetic implants, regenerative scaffolding, or bony reconstruction. Many techniques are derived from experience with cisgender patients, but are adapted with special considerations to differing anatomy between cisgender and transgender men and women. Currently, facial masculinization is less commonly sought than feminization, but demand is likely to increase as techniques are refined and made available.

Chronic heart failure in patients undergoing major head and neck surgery: A hospital-based study.

OBJECTIVE: To investigate the effects of chronic heart failure on various post-operative outcomes in head and neck cancer patients undergoing major cancer surgery. STUDY DESIGN: For this retrospective cohort study of patients undergoing major head and neck cancer surgery, a sample of 10,002 patients between 2017 and 2019 were identified through the Nationwide Inpatient Sample. SETTING: Patients were selected as undergoing major head and neck cancer surgery, defined as laryngectomy, pharyngectomy, glossectomy, neck dissection, mandibulectomy, and maxillectomy, then separated based on pre-surgical diagnosis of chronic heart failure. METHODS: The effects of pre-operative chronic heart failure on post-surgical outcomes in these patients were investigated by univariable and multivariable logistic regression using ICD-10 codes and SPSS. RESULTS: A diagnosis of chronic heart failure was observed in 265 patients (2.6 %). Patients with chronic heart failure had more preexisting comorbidities when compared to patients without chronic heart failure (mean ± SD; 4 ± 1 vs. 2 ± 1). Multivariable logistic regression showed that chronic heart failure patients had significantly greater odds of dying during hospitalization (OR 2.86, 95 % CI 1.38-5.91) and experiencing non-routine discharge from admission (OR 1.89, 95 % CI 1.41-2.54) after undergoing major head and neck cancer surgery. CONCLUSION: Chronic heart failure is associated with greater length of stay and hospital charges among head and neck cancer patients undergoing major head and neck cancer surgeries. Chronic heart failure patients have significantly greater rates of unfavorable post-operative outcomes, including death during hospitalization and non-routine discharge from admission.

Clarification of the margin status by the multidisciplinary tumor board following transoral robotic surgery for p16 positive oropharyngeal squamous cell carcinoma.

Objectives: Margin status interpretation following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) is challenging. This study aims to assess the discrepancy between status of margins as reported by the pathologist versus as determined by multi-disciplinary team review (MDTB). Methods: A retrospective study of 57 patients with OPSCC who underwent TORS from January 2010 to December 2016 was conducted. Our primary outcome measure was the discrepancy between the surgical specimen margins as described in the pathology report versus final margin status that was determined after the multi-disciplinary team discussion. Fisher's exact test was used. Results: Based on the pathologist-report, 29 subjects (51%) had positive margins, compared to 2 (4%) after multi-disciplinary team discussion. Receipt of chemotherapy correlated with final margin status as determined by MDTB, not with initial main specimen margins (p = .02 and p = .08, respectively). With a median follow up of 28.4 months, two subjects (4%) had loco-regional recurrence. Conclusion: Following TORS, there was a significant discrepancy between status of margins as reported by the pathologist versus as determined by MDTB review. Chemotherapy was avoided in 93.1% of cases that were originally reported as positive margins by the pathologist with an acceptably low recurrence rate. Level of evidence: 4.