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Introduction: Microbiome research has predominantly focused on the oral cavity and oropharynx's role in disease, while the upper airway, specifically the larynx and trachea, has been relatively overlooked. Examining the microbial communities in these regions can shed light on how dysbiosis influences diseases and their management. This review evaluates laryngotracheal microbial compositions in both healthy and diseased patients. Methods: We conducted a systematic review in EMBASE, MEDLINE, and Cochrane Central databases, yielding 1383 studies in the initial search. Inclusion criteria involved participants aged over 18 years and the use of next‐generation 16s ribosomal sequencing methods. Results: We included 10 studies—seven focused on larynx sequencing and four on trachea sequencing (one investigated both sites). In a healthy larynx, diverse species such as Streptococcus, Cloacibacterium, Prevotella, and Helicobacter were found. Benign laryngeal diseases exhibited reduced microbial diversity, mainly dominated by Streptococcus. Subglottic stenosis patients showed diminished diversity in both idiopathic and iatrogenic scars. Laryngeal squamous cell carcinoma displayed increased diversity, primarily featuring Fusobacterium. Among non‐respiratory‐compromised surgery patients, the tracheal microbiome was more diverse in diabetics and those later developing lower respiratory infections. Pneumonia patients exhibited an abundance of Prevotella and Streptococcus, linked to an increased 28‐day survival rate, while Streptococcus and Haemophilus abundance correlated with successful extubation. Conclusions: The laryngotracheal region hosts a unique microbial community influenced by both benign and malignant conditions. Many lesions remain unexplored, underscoring the need for future studies encompassing diverse laryngotracheal conditions. Clinical trials assessing microbiome modifications may unveil novel therapeutic avenues. Level of Evidence: NA Laryngoscope, 134:4167–4175, 2024 [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common cancer of the female reproductive system in the United States and the second most common cancer of the female reproductive system worldwide. Treatment typically consists of upfront surgery. Postoperative therapy may include adjuvant radiation therapy and/or systemic therapy based on unique patient and pathologic characteristics. In this review, we explore the ways in which patient and tumor characteristics, current and emerging radiation technologies, and other cancer-directed treatments may be considered in developing personalized radiotherapy regimens for patients with endometrial cancer. Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic precipitated drastic changes in cancer care. Its impact on the U.S. head and neck cancer population has yet to be fully understood. This study aims to understand the impact of pandemic-related changes on the head and neck cancer population. An observational study of head and neck cancer patients at a single institution during the spring of 2020 and 2019 was performed. Clinical characteristics and survival outcomes were analyzed. In 2020, 54 head and neck cancer patients were evaluated in the department of radiation oncology vs. 74 patients seen in 2019; 42% of the patients were female in 2019 versus 24% in 2020 (p = 0.036). The median follow-up time was 19.4 and 31 months for 2020 and 2019, respectively. After adjusting for stage, the relapse-free survival probability at 6 and 12 months was 79% and 69% in 2020 vs. 96% and 89% in 2019, respectively (p = 0.036). There was no significant difference in the overall survival, with 94% and 89% in 2020 and 2019, respectively (p = 0.61). Twenty-one percent of patients received induction chemotherapy in 2020 versus 5% in 2019 (p = 0.011); significantly more treatment incompletions occurred in 2020, 9% vs. 0% in 2019 (p = 0.012). Moreover, the stage-adjusted RFS differed between cohorts, suggesting head and neck cancer patients seen during the initial wave of COVID-19 may experience worse oncologic outcomes. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a leading cause of morbidity and mortality globally. Despite significant advances in well-established treatment techniques, prognosis for advanced-stage HNSCC remains poor. Recent, accumulating evidence supports a role for immunotherapy in HNSCC treatment. Radiation therapy (RT), a standard treatment option for HNSCC, has immunomodulatory and immunostimulatory effects that may enhance the efficacy of immunotherapy. In several cancer types, combining RT and immunotherapy has been shown to improve tumor response rates, increase survival, and reduce toxicity compared to traditional chemotherapy and radiation therapy. This review provides a timely overview of the current knowledge on the use of RT and immunotherapy for treating HNSCC. It highlights the potential advantages of combining these therapies, such as improved tumor response rates, increased survival, and reduced toxicity. The review also discusses the challenges that need to be addressed when redefining the standard of care in HNSCC, and proposes further research to optimize treatment combinations, minimize radiation-induced toxicity, and identify suitable patient populations for treatment. [ABSTRACT FROM AUTHOR]

The emergence of immune checkpoint inhibitors (ICIs) as a pillar of cancer treatment has emphasized the immune system's integral role in tumor control and progression through cancer immune surveillance. ICIs are being investigated and incorporated into the treatment paradigm for lung cancers across stages and histology. To date, definitive concurrent chemoradiotherapy followed by consolidative durvalumab is the only National Comprehensive Cancer Network's recommended treatment paradigm including radiotherapy with ICI in lung cancers, although there are other recommendations for ICI with chemotherapy and/or surgery. This narrative review provides an overall view of the evolving integration and synergistic role of immunotherapy and radiotherapy and outlines the use of immunotherapy with radiotherapy for the management of small cell lung cancer and non-small cell lung cancer. It also reviews selected, practice-changing clinical trials that led to the current standard of care for lung cancers. [ABSTRACT FROM AUTHOR]

Objective(s): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. Methods: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. Results: Eighty‐two patients (38 young, 44 old) were included in this study. Median follow‐up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5‐year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis‐free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease‐specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in‐field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03). Conclusions: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in‐field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. Level of Evidence: 3 Laryngoscope, 133:1110–1121, 2023 [ABSTRACT FROM AUTHOR]

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately one third of patients with head and neck cancer are older adults. The number of older adults with head and neck cancer continues to rise especially as life expectancy increases. However, this population remains significantly underrepresented in clinical trials. Due to this, there is no clear consensus regarding the optimal treatment for older adults with head and neck cancer. In general, older adults are a complex cohort due to variations in functional and performance status, medical comorbidities, and medication management. Treatment for head and neck cancer involves surgery, radiation therapy, systemic therapy, or a combination. These treatments are highly demanding. Additionally, they are associated with toxicity which can be especially difficult for older adults to tolerate. This may lead to treatment interruptions and compromised outcomes. In order to understand the optimal treatment for older adults with head and neck cancer, novel predictive scores are being developed. Additionally, ongoing clinical trials are investigating less intensive treatments for older adults. This review provides an overview of current clinical data, treatment considerations, and future areas of investigation for older adults with head and neck cancer. Thirty percent of patients with head and neck squamous cell carcinoma (HNSCC) are at least 70 years of age. This number continues to rise as life expectancy continues to increase. Still, older adults with HNSCC remain underrepresented in clinical trials, resulting in ambiguity on optimal management. Older adults are a complex patient population, often requiring increased support due to issues relating to functional and performance status, medical comorbidities, and medication management. Furthermore, in older adults with HNSCC, many of these conditions are independently associated with increased toxicity and worse outcomes. Toxicity in the older adult remains difficult to predict and to understand, and as treatment decisions are based on treatment tolerability, it is essential to understand the toxicities and how to minimize them. Novel predictive scores are being developed specifically for older adults with HNSCC to understand toxicity and to assist in personalized treatment decisions. There are clinical trials presently underway that are investigating shortened radiation courses and novel, less toxic systemic treatments in this population. In the forthcoming sections, we provide a detailed overview of the clinical data, treatment paradigms, and considerations in this population. This review provides a comprehensive overview of existing clinical data and clinical considerations in the older adult head and neck cancer population. Additionally, we provide a detailed overview of pertinent current and ongoing clinical trials, as well as future areas for investigation. [ABSTRACT FROM AUTHOR]

Purpose: The number of elderly patients with head and neck squamous cell carcinoma (HNSCC) continues to grow. Management of this cohort remains poorly defined. We investigated treatment tolerability and clinical outcomes in this underrepresented population. Methods: We identified patients aged ≥70 with nonrecurrent, nonmetastatic HNSCC treated curatively from 2007‐2018 and analyzed clinical covariates. Results: Two hundred and twenty patients with a median age of 75 (interquartile range:72‐80) were identified. Age and comorbidities were not correlated with toxicity (P ≥.05). Patients who experienced a treatment interruption had significantly greater weight loss (P =.042) and worse overall survival (OS) (P <.001), but not worse disease‐specific survival (P =.45), or locoregional control (P =.21). Conclusions: Treatment interruptions were associated with weight loss and worse OS, but not disease related outcomes, suggesting an interruption in the elderly may be a surrogate for another issue. In sum, our data should guide clinical trial design to benefit this growing, neglected cohort. [ABSTRACT FROM AUTHOR]

Purpose: For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy., Methods and Materials: We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival., Results: The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention., Conclusions: Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population., Competing Interests: Marshall Posner reports royalties or licenses from Beth Israel Deaconess Medical Center; consulting fees from Naveris, Hookipa, Cel-SCI; participation on a Data Safety Monitoring Board or Advisory Board with Merck, Calliditas, Frizent, and Vivant Therapeutics. The remaining authors declare that they have no conflict of interest., (© 2023 The Author(s).)

The use of prophylactic cranial irradiation (PCI) remains an important component in the management of small cell lung cancer (SCLC). This is due to the high rates of subclinical brain metastases at the time of diagnosis. Following a response to initial treatment, PCI historically has been associated with improvements in overall survival and decreased development of brain metastases in patients with limited stage (LS-SCLC) and extensive stage (ES-SCLC) SCLC. However, PCI is commonly withheld in these settings in favor of observation, largely due to its association with cognitive sequelae following treatment. While randomized data has demonstrated that in patients with ES-SCLC, PCI may be withheld in favor of close MRI surveillance without a detriment in overall survival or cognitive functioning, these patients did not undergo formal neuropsychological assessments. In recent years, cognitive sparing techniques incorporated into whole brain radiation therapy and PCI, such as the addition of memantine and hippocampal avoidance, have demonstrated significant improvements in cognitive outcomes. As the overall survival in patients with SCLC continues to improve due to the incorporation of novel systemic therapies (e.g., immune checkpoint inhibitors), the role of PCI and maximizing quality of life remains a highly relevant topic. This article reviews the role of PCI and cognitive-sparing techniques in the management of SCLC.

Prostate cancer treatment has substantial effects on sexual health and function. Sexual function is a vital aspect of human health and a critical component of cancer survivorship, and understanding the potential effects of different treatment modalities on sexual health is crucial. Existing research has extensively described the effects of treatment on male erectile tissues necessary for heterosexual intercourse; however, evidence regarding their effects on sexual health and function in sexual and gender minority populations is minimal. These groups include sexual minority - gay and bisexual - men, and transgender women or trans feminine people in general. Such unique effects in these groups might include altered sexual function in relation to receptive anal and neovaginal intercourse and changes to patients' role-in-sex. Sexual dysfunctions following prostate cancer treatment affecting quality of life in sexual minority men include climacturia, anejaculation, decreased penile length, erectile dysfunction, and problematic receptive anal intercourse, including anodyspareunia and altered pleasurable sensation. Notably, clinical trials investigating sexual outcomes after prostate cancer treatment do not collect sexual orientation and gender identity demographic data or outcomes specific to members of these populations, which perpetuates the uncertainty regarding optimal management. Providing clinicians with a solid evidence base is essential to communicate recommendations and tailor interventions for sexual and gender minority patients with prostate cancer., (© 2023. Springer Nature Limited.)

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.

Objectives Chemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates. Methods Records for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher's exact test. Results We included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19). Conclusion In this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Nehlsen et al.)

Determining the density and morphology of dendritic spines is of high biological significance given the role of spines in synaptic plasticity and in neurodegenerative and neuropsychiatric disorders. Precise quantification of spines in three dimensions (3D) is essential for understanding the structural determinants of normal and pathological neuronal function. However, this quantification has been restricted to time- and labor-intensive methods such as electron microscopy and manual counting, which have limited throughput and are impractical for studies of large samples. While there have been some automated software packages that quantify spine number, they are limited in terms of their characterization of spine structure. This unit presents methods for objective dendritic spine morphometric analysis by providing image acquisition parameters needed to ensure optimal data series for proper spine detection, characterization, and quantification with Neurolucida 360. These protocols will be a valuable reference for scientists working towards quantifying and characterizing spines. © 2016 by John Wiley & Sons, Inc., (Copyright © 2016 John Wiley & Sons, Inc.)