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Oral Mucositis (OM) continues to be an oncologic challenge in the context of antineoplastic therapy for head and neck cancer (HNC) treatment. It is a dose-limiting toxicity of chemotherapy and radiation treatment and negatively impacts quality of life and cancer treatment efficacy. Significant effort in the field of OM has been made to help alleviate its symptoms and its subsequent clinical and economic impact. Despite these advances, the treatment of oral mucositis remains difficult and focuses on palliative measures. There are, however, many promising new biological targets currently undergoing investigation to ameliorate or help prevent the toxicity of OM in HNC. Some of these targets undergoing investigation in phase 2 and 3 clinical trials are further highlighted along with the pathobiology of OM, clinical course, prevention, and management measures. [ABSTRACT FROM AUTHOR]

The larynx is an organ of the upper aerodigestive tract that is involved in many critical functions such as breathing, speaking, and swallowing. As a result, both larynx cancer and its treatment may significantly affect quality of life. The management of laryngeal cancer has focused on improving survival while preserving the function of the organ. This manuscript focuses on the use of chemotherapy and radiation therapy as a non-surgical approach and potential organ preservation strategy for patients with advanced larynx cancer. We review the key clinical data on the following treatment courses: (1) induction chemotherapy followed by definitive radiation therapy, (2) concurrent chemotherapy and radiation, and (3) induction chemotherapy followed by concurrent chemo-radiation. We also review the clinical data on organ preservation for patients with hypopharynx cancers. Results from phase III studies suggest that patients with advanced T4 cancers have better outcomes with a primary surgical approach, while for patients with T2N+ and T3 tumors, definitive concurrent chemotherapy and radiation or induction chemotherapy followed by definitive radiation therapy are acceptable options. Choosing the optimal treatment strategy depends on patients' desires, tumor extent, and adequate follow-up to detect early recurrences in cases of larynx preservation treatments. To proceed with an organ preservation strategy, the patient should have a good pre-treatment larynx function, and there must be a high level of skill and cooperation among various disciplines. [ABSTRACT FROM AUTHOR]

Fibrocytes, a group of bone marrow-derived mesenchymal progenitor cells, were first described in 1994 as fibroblast-like, peripheral blood cells that migrate to regions of tissue injury. These cells are unique in their expression of extracellular matrix proteins concomitantly with markers of hematopoietic and monocyte lineage. The involvement of fibrocytes and the specific role they play in the process of wound repair has been a focus of study since their initial description. Fibrocytes contribute to the healing repertoire via several mechanisms; they produce a combination of cytokines, chemokines, and growth factors to create a milieu favorable for repair to occur; they serve as antigen presenting cells (APCs); they contribute to wound closure; and, they promote angiogenesis. Furthermore, regulatory pathways involving serum amyloid P, leukocyte-specific protein 1, and adenosine A2A receptors have emphasized the significant role that fibrocytes have in wound healing and fibrosis. The therapeutic targeting of fibrocytes holds promise for the augmentation of wound repair and the treatment of different fibrosing disorders. [ABSTRACT FROM AUTHOR]

The microRNA (miRNA) pathway represents an integral component of the gene regulation circuitry that controls development. In recent years, the role of miRNAs in embryonic stem (ES) cells and mammalian embryogenesis has begun to be explored. A few dozens of miRNAs expressed in mammalian ES cells, either exclusively or nonexclusively, have been cloned. The overall role of miRNAs in ES cells and embryonic development has been assessed by examining the effect of knocking out Dicer, an RNase III enzyme required for miRNA and small interfering RNA biogenesis, as well as DGCR8, a nuclear protein specifically involved in miRNA biogenesis. In addition, the role of a cluster of miRNAs specifically expressed in ES cells, the miR-290 -295 group, has been investigated by the knock-out approach. These analyses have revealed the crucial role of miRNAs in ES cell differentiation, lineage specification, and organogenesis, especially neurogenesis and cardiogenesis. Systematic investigation of the role of miRNAs in ES cells and embryos will allow us to find missing pieces of the mosaic of early development. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy—all focused on improving survival while preserving organ function. Despite changes in smoking patterns resulting in a declining incidence of laryngeal cancer, the overall outcomes for this disease have not improved in the recent past, likely due to changes in treatment patterns and treatment-related toxicities. Here, we review emerging concepts and novel strategies in the use of radiation therapy in the management of laryngeal squamous cell carcinoma that could improve the relationship between tumor control and normal tissue damage (therapeutic ratio). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the effect of definitive or adjuvant concurrent chemoradiation (CRT) among elderly patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Materials and Methods: We retrospectively analyzed 150 elderly LA HNSCC patients (age ≥70) at a single institution. Demographics, disease control outcomes, and toxicities with different chemotherapy regimens were reviewed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) estimates. Results: Median age at diagnosis was 74 years (range 70–88). Of the cohort, 98 (65.3%) patients received definitive and 52 (34.7%) received adjuvant CRT; 44 (29.3%) patients received weekly carboplatin and paclitaxel, 43 (28.7%) weekly cetuximab, 33 (22%) weekly carboplatin, and 30 (20%) weekly cisplatin. The OS at 2 years was 70% (95% confidence interval [CI]: 63–79%), and PFS at 2 years was 61% (95% CI: 53–70%). There was no significant difference in OS or PFS between definitive and adjuvant CRT (p = 0.867 and p = 0.475, respectively). Type of chemotherapy regimen (single-agent carboplatin vs. others) (95% CI: 1.1–3.9; p = 0.009) was a key prognostic factor in predicting OS in multivariable analysis. Concurrent use of cetuximab was associated with increased risk of PEG tube dependence at 6 months (p < 0.001). Conclusions: Management of LA HNSCC in the elderly is a challenging scenario. Our study shows that CRT is a feasible treatment modality for elderly patients with LA HNSCC. We recommend CRT with weekly cisplatin or weekly carboplatin and paclitaxel. A chemotherapy regimen should be carefully selected in this difficult to treat population. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p =.003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p <.001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p <.001 and p =.024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84–6.67; p <.001) and OS (aHR 2.00, 95%CI 1.04–3.88; p =.039) compared to HER2-negative tumors. Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease. • Twenty six percent of stage I uterine serous carcinoma tumors were HER2 positive. • HER2 positivity was associated with a 3 fold greater risk of disease recurrence. • HER2 is a potential prognostic biomarker for women with early stage disease. [ABSTRACT FROM AUTHOR]

Purpose  Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Methods and Materials  Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan–Meier log-rank. Results  Median follow-up time was 59 months (range: 5.2–236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% (p  = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients (p  = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5–235 months). Conclusion  In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX–XII, which would help in establishing RT limiting doses for organs at risk (OAR). Methods: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX–XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. Results: We successfully developed a contouring atlas for CNs IX–XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66–70Gy). The median CN (IX–XI) and (XII) volumes were 10c.c (range: 8–12c.c) and 8c.c (range: 7–10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX–XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX–XI) and (XII) were 72Gy (range: 66–77) and 71Gy (range: 64–78), respectively. Conclusions: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of oropharynx cancers usually requires radiation, chemotherapy, surgery, or a combination of all three. Although these treatments are effective, they can cause both short- and long-term side effects, particularly when more than one treatment option is used. Robotic surgery is now an option for patients with oropharynx cancers, but it is not clear how many patients will require additional treatment with radiation, or combined chemotherapy and radiation, after surgical treatment. In this study we used a large national database of oropharynx cancer patients and found that two-thirds of patients who were treated with robotic surgery required radiation therapy and one-third required chemotherapy with radiation. In addition, we found that the true tumor stage of the patients in this study was often higher than was initially thought prior to surgery. Finally, patients treated at high volume surgical centers were more likely to have more of their tumor removed compared to those at low volume facilities. Better survival quality of oropharynx cancer patients could be achieved by improving pre-surgical selection of patients so that the number of treatment modalities is reduced. Trans-oral robotic surgery (TORS) has emerged as an important surgical treatment option in the management of human papillomavirus (HPV)-positive and -negative oropharynx cancer. However, treatment selection is paramount to ensure that patients will not require multimodality adjuvant therapy. In this study, we determined predictors of adjuvant therapy in TORS-treated patients. The National Cancer Database (NCDB) was used to identify patients with newly diagnosed clinical T1-T4, N0-N3 oropharyngeal squamous cell carcinoma who underwent TORS between 2010–2016. Kaplan–Meier survival analysis was used to estimate overall survival (OS). A total of 2999 patients were studied, and the five-year OS for the entire cohort was 82.5%, and for HPV-positive and -negative cohorts it was 88.3% and 67.9%, respectively (p < 0.001). Among all patients treated with TORS, 35.1% of patients received no additional treatment, 33.5% received adjuvant radiation alone (RT), and 31.3% received adjuvant chemoradiation. The N stage was pathologically upstaged in 629 (20.9%) patients after TORS. Patients treated at higher-volume centers were more likely to have negative surgical margins (OR: 0.96, 95% CI: 0.94, 0.98, p < 0.001), but this did not influence the receipt of adjuvant therapy. The high rate of adjuvant multimodality treatment after TORS suggests a need for improved patient selection. Limitations of this study, including lack of data on loco-regional control, progression free survival, acute and late toxicities, and utilization of pretreatment PET/CT imaging, should be addressed in future studies. [ABSTRACT FROM AUTHOR]